#38990: Pathophysiology: The Hematologic System

Because many medications interfere with normal hematologic functioning, the patient history should make note of any prescribed or over-the-counter medications the patient takes. Antineoplastic drugs as well as some antibiotics such as chloramphenicol causes bone marrow suppression. Sedatives, hypnotics, analgesics, laxatives, and aspirin may cause or worsen hematologic abnormalities [11].

The use of aspirin is so common that both the patients and the nurse can overlook or disregard its significance. Aspirin reduces platelet aggregation (the ability of platelets to be called to an injury site), increasing the potential for bleeding, especially in patients with compromised hematologic functioning. Thus, determining the patient's use of aspirin and noting when the patient last used aspirin are especially important. Alcohol consumption must also be assessed. Alcohol abuse damages the liver: Liver damage alters the production of clotting factors [12].

Exposure to chemicals increases the incidence of hematologic disorders. Patients may come into contact with chemicals through their jobs or avocations, by living in a contaminated area, or by using certain cosmetics. At increased risk for developing hematologic disorders are patients who are continuously exposed to asbestos, asphalt, industrial dyes, lead, and dry-cleaning fluid. Dyes used in fabrics and even on the patient's own hair may cause hematologic injury. Patients living close to industrial plants are also at increased risk [12].

Exposure to radiation also increase the incidence of hematologic disorders. Patients who live close to nuclear power plants or work with radioactive materials may be at increased risk, as are patients who have been accidentally exposed to high amounts of radiation or purposely exposed for therapeutic purposes [12].

Elicit the patient's health history. Allergies, pre-existing medical conditions such as liver disease, and knowledge about past immune response should be documented. Note previous diagnoses of blood disorders such as anemia or mononucleosis or gastrointestinal malabsorption problems. Determine how many and what kinds of infections the patient has had. What part of the body had been affected: Do the infections recur? Do they respond to treatment? What symptoms are evident (Is the temperature elevated? Is there a pattern? Does the patient have night sweats?)? Measure the patient's C Reactive Protein (CPR). An elevation indicates a bacterial infection [1].

Ask about the patient's bleeding tendencies after injury, surgery, or dental extraction: Has the patient had any problems with abnormal bleeding or bruising? The patient's history of receiving blood transfusions – the number of transfusions, why they were administered, and whether there were any complications during or following the transfusion — should be documented. Ask about the patient's surgical history. In particular, the fact that a patient has undergone a splenectomy or surgical resection of the duodenum may give valuable information about blood dyscrasias. For example, knowing that a patient has a past history of splenectomy might also reveal the reason for splenectomy (usually trauma or spherocytosis). Removal of the stomach and duodenum interferes with the patient's ability to properly absorb vitamin B and sets the stage for a surgically induced pernicious anemia. Information about the patient's postoperative healing may give clues to the patient's bone marrow integrity and competence of immune response [1].

The dietary history may provide important clues about the causes of some hematologic disorders. Information about intake of iron, vitamin B12, and folic acid may be revealed in the patient's report of the kinds of foods they eat regularly. High alcohol intake may suggest why a patient has a diminished appetite or vitamin deficiencies. A dietary history that reveals low intake of foods high in iron indicates the cause of the patient's anemia; knowing that a patient takes vitamin B suggests the possibility of pernicious anemia. Although dietary history alone cannot diagnose hematologic abnormalities, it can aid in both the diagnosis and management of disorders of the blood and the blood-forming organs [13].

Inspection and palpation of the skin can give valuable information about the status of the patient's hematologic system. Patients with hepatic or biliary disease with elevated bilirubin levels may have a hemolytic anemia (destruction of erythrocytes), which manifests itself as jaundice. Patients having reduced hemoglobin levels may be cyanotic. Patients with polycythemia vera frequently have ruddy complexions [14,15].

Color of the patient's skin depends not only on the level of the patient's hemoglobin but also on the amount of pigmentation in the skin. If patients have darkly pigmented skin, disorder-induced color changes may be obscured by the patient's natural skin tones or hues. Hence, skin color cannot be used as the sole indicator of overall oxygenation of body tissues. To assess skin color properly in these situations, closely inspect the patient's oral mucosa, conjunctivae, and nail beds. Another good way to assess oxygenation to tissues without interference from skin pigmentation or hemoglobin level is to inspect the color of palmar creases. Have the patient open the hand with fingers fully extended. If oxygenation to the body tissues is adequate, the palmar creases should be pink [14,15].

Patients having problems with platelets and those with clotting-mechanism dysfunction have alterations in skin integrity that can be observed on physical examination. Frequently, the nurse observes purpura (redness), ecchymosis, or petechiae. Ecchymosis (hemorrhagic spots larger than petechiae) may be dark purplish, brown-yellow, or greenish, depending on the age of the lesion, and they may or may not be precipitated by a bump or injury. Lesions can be flat or elevated and may be painful or tender to palpation. Petechiae are more common when patients have disorders of platelet functions, life span, or decreased platelet numbers. Petechiae can occur over any part of the skin but are most common when pressure has been applied to a body part (after application of a tourniquet or blood pressure cuff). Petechiae are usually flat, nontender lesions that do not blanch with pressure. Ecchymoses are also seen [14,15].

Pruritus in cells with Hodgkin disease or non-Hodgkin lymphoma may be so severe that the skin is excoriated from scratching. Leg ulcers in patients with sickle cell disease are most frequent over the medial and lateral malleoli. Ulcerations may be present at the time of the physical examination, or the nurse may observe healed scars over the lower extremities [14,15].

Jaundice of the sclera may accompany jaundice of the skin. Retinal or scleral hemorrhages may be observed with thrombocytopenia. Conjunctival pallor can be seen in many of the anemias [16].

Tissue oxygenation also may be assessed using the gingivae of the mouth as the guide. With optimal tissues oxygenating, the gingivae appear pink, but pallor indicates inadequate oxygenation. The tongue of a patient with pernicious anemia or iron-deficiency anemia may be smooth. Nutritional deficits, in general, may cause the tongue to become red and smooth [16].

Bleeding or oozing from the gums or teeth may occur in any patient having a bleeding disorder whether due to platelet abnormalities or clotting-factor deficiencies. Infections and lesions of the oral mucosa frequently develop in patients with leukopenia. Inspect the patient's mouth daily, noting any of these alterations in skin integrity [16].

The lymph nodes make up part of the lymphoreticular system that is responsible for the body's defense against invading pathogens. Lymph node enlargement is frequent among patients with hematologic and lymphoreticular disorders, particularly malignant ones. In physical assessment, it is important to note whether the lymph nodes are mobile or fixed, tender or painless, or enlarged upon palpation [17].

Sternal tenderness or pain upon palpation may accompany the leukemias and the lymphomas in the presence of a mediastinal mass. Auscultation of heart sounds may reveal tachycardia and cardiac murmurs if the patient is severely anemic. The tachycardia and murmurs usually resolve following the administration of packed red blood cells [17].

Auscultation of the lungs may reveal diminished or absent breath sounds that may be related to a malignant pleural diffusion or tumor obstruction. The presence of adventitious sounds may indicate pulmonary bleeding, pulmonary edema, or pneumonia. Decreased diaphragmatic excursion (movement) may be due to splenomegaly or hepatomegaly [17].

Patients with disorders of the blood and blood-forming organs frequently have hepatomegaly, splenomegaly, or both. The size of these organs can be ascertained using the skills of percussion and palpation of the liver and spleen. With percussion, the liver heights are 4–8 cm in the midsternal line and 6–12 cm in the right midclavicular line. When the liver is enlarged, the span of liver dullness is increased [18].

The spleen can also be identified and splenic size estimated from percussion. The spleen is palpated as a small oval area of dullness over the tenth rib and posterior to the midaxillary line. An enlarged area of dullness may indicate increased splenic size [18].

Liver and spleen size can also be assessed using palpation. An increase in liver size, with or without tenderness, is a significant finding in the blood disorders. The spleen normally is not palpable in adult patients. The finding of splenomegaly or simply palpating the tip of the spleen in the adult patient is significant because splenomegaly is present in many hematologic disorders such as chronic granulocytopenic leukemia [18].

Musculoskeletal system abnormalities are not uncommon in patients with disorders of the blood and blood-forming organs. Visible joint deformities are present in patients with hemophiliac and sickle cell disease. Limitation of the normal range of motion may accompany the joint deformity. The patient may experience either active or passive pain with movement, and tenderness may be triggered by palpation [19].

Patients with vitamin B12 deficiency, such as those with pernicious anemia, can have neurologic dysfunction manifested as cerebral, spinal cord, or peripheral nerve involvement. Leukemic patients with meningeal involvement may have headache, visual impairment, or cranial nerve involvement. Patients who have neutropenia or thrombocytopenia may have neurologic dysfunction due to CNS infection or bleeding [19].

The complete blood count (CBC) with white blood cell (WBC) differential is one of the most important tests for evaluating the status of the patient's hematologic system; the CBC with differential provides a measure of the blood's ability to carry and transport oxygen (erythrocyte measurement) and to resist invading infectious organisms (leukocyte measurement). The CBC with differential usually requires approximately 7 mL of venous blood [20].

The CBC erythrocyte measurement consists of a red blood cell count, hemoglobin, hematocrit, various erythrocyte indices (such as mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration), and a stained red cell examination (film or peripheral blood smear). The CBC leukocyte measurement includes a WBC count. In addition to the total WBC count, the CBC with differential determines the various types of leukocyte cells (neutrophils, basophils, eosinophils, granulocytes, lymphocytes, and monocytes). Neutrophils serve as the primary defense against infection. These erythrocyte and leukocyte measurements are discussed individually. In some laboratories and institutions, a platelet count is considered part of the CBC [20].

The red blood cell count (RBC), or erythrocyte count, is the measurement of the number of erythrocytes circulating in 1 mcL of whole blood. Factors or disease states that result in an elevation of the erythrocyte count are high altitude, hemoconcentration resulting from shock, trauma, or hemorrhage; anoxia and polycythemia vera. These erythrocyte counts may be decreased in anemia, Hodgkin disease, or leukemia [20].

Hemoglobin (Hb) is the main component of the erythrocyte or RBC. Disease states or pathologic conditions that contribute to an elevation in the hemoglobin level include polycythemia or erythrocytosis, hemoconcentration in shock or immediately after hemorrhage, and high altitude. Hemoglobin levels are decreased in anemia resulting from increased blood distribution or decreased RBC production. It is indicative of iron-deficiency anemia [20].

The hematocrit (Hct) or packed cell volume (PCV) measures the percentage of a given volume of whole blood occupied by erythrocytes. Disorders that result in an elevated hematocrit are polycythemia vera and hemoconcentration for shock, surgery, or hemorrhage. A decrease in hematocrit can be caused by anemia resulting from diminished blood production or increased red blood cell destruction, the leukemias, and the lymphomas. If hematocrit is done separately for the CBC, a sample of blood may be obtained by a finger prick [20].

The erythrocyte indices are three different values that examine the size, weight, and hemoglobin content of the average erythrocyte. These three values—mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC)—reflect red cell morphology. Abnormalities in the erythrocyte indices in conjunction with the stained red cell examination provide a way of classifying anemias and suggesting their possible causes. Values are increased in folate or vitamin B12 deficiency, liver disease, alcoholism, sprue, and antimetabolite therapy. Values are decreased in anemia from chronic blood loss, iron-deficiency anemia, pernicious anemia, and thalassemia. The function of erythrocytes is to carry oxygen [20].

The stained blood smear is examined to determine abnormalities in the size, shape, or structure of erythrocytes as well as the staining properties. This microscopic examination helps in the diagnosis of anemia, leukemia, and thalassemia and in determining harmful effects of chemotherapy and radiation [20].

The total WBC count, or leukocyte count, determines the number of circulating white blood cells in 1 mcL of whole blood. An elevated WBC or (Leukocytosis) can accompany anoxia, anemia, infections, and mononucleosis. Leukemias, polycythemia vera, and transfusion reactions may also occur immediately following trauma or hemorrhage. Leukopenia, or a decreased WBC, may accompany agranulocytosis, anemia, hypersplenism, and leukemia [20].

The differential WBC count determines the distribution of the kinds of WBCs. The differential WBC count is usually reported in percentages, which should add up to 100. The differential WBC count classifies leukocytes as monocytes, lymphocytes, or granulocytes. Granulocytes are further classified as neutrophils, eosinophils, or basophils, Neutrophils are divided into and reported as either banded (a juvenile form) or segmented (the mature neutrophil). The differential not only reports leukocyte morphology but also identifies and reports immature or atypical leukocytes. An increase in the number of immature leukocytes is often called "a shift to the left." The nursing history should assess the patient's exposure to chemicals and the medication history [20].

A rise in the percentage of neutrophils (neutrophilia) may occur in any malignancy, crushing injury, the leukemias, malignant lymphoma, polycythemia vera, the hemolytic anemias, and hemolysis due to transfusion reaction. The percentage of circulating neutrophils (neutropenia) can be decreased in infectious mononucleosis, agranulocytosis, the leukemias, aplastic anemia, pernicious anemia, multiple myeloma, and vitamin B12 deficiency. Most leukocytes are neutrophils. The function of leukocytes is to protect against infectious agents [20].

Lymphocytosis, an elevation in the percentage of lymphocytes, accompanies the lymphocytic leukemias, infectious mononucleosis, agranulocytosis, aplastic anemia, multiple myeloma, and lymphosarcoma. Lymphopenia, or a decreased number of lymphocytes, may be present in Hodgkin disease and in the acute leukemias. An elevation of monocytes, or monocytosis, may be the bone marrow's response to agranulocytosis, Hodgkin disease, monocyte leukemias, non-Hodgkin lymphoma, and hemolytic anemia. Eosinophilia (elevated eosinophils) accompanies eosinophilic leukemia, Hodgkin disease, a pernicious anemia, polycythemia vera, and sickle cell disease in some patients. Basophils may be elevated (basophilia) in chronic myelogenous leukemia, the hemolytic anemias, Hodgkin disease, and polycythemia vera. The patient should seek medical assistance at the first sign of an infection [20].

The erythrocyte sedimentation rate (ESR) is the rate at which erythrocytes in anticoagulated whole blood settle to the bottom of a tube. The ESR great value is to indicate the presence of an active inflammatory disease process. The ESR is elevated in leukemia, malignant lymphoma, Hodgkin disease, severe anemia, and agranulocytosis but may be within the normal range in polycythemia and sickle cell disease. Hyperchromic is a term used to describe erythrocytes with color indicating a high hemoglobin content [20].

The erythrocyte osmotic fragility test measures the erythrocyte's ability to resist hemolysis in a hypotonic solution. Cells that hemolyze in a relatively high concentration of saline (barely hypotonic) have an increased osmotic fragility. Disease states accompanied by an increased osmotic fragility are acquired hemolytic anemia, hemolytic disease due to the blood-type incompatibility, pernicious anemia, symptomatic hemolytic anemia due to Hodgkin disease, and leukemia. Iron-deficiency anemia, anemia, polycythemia vera, sickle cell disease, and thalassemia major are accompanied by decreased osmotic fragility. Erythropoietin is the hormone that regulates the production of erythrocytes [20].

The reticulocyte count is considered the most useful test in the evaluation of anemia and is a good index of effective erythropoiesis and bone marrow response to anemia. Reticulocytes are uninucleated, immature RBCs capable of oxygen transport. They remain in the bone for 24 to 48 hours, after which they are mature. An elevated reticulocyte count, or reticulocyte, occurs in disease states or conditions that cause a relative anoxic or hypoxic state in the patient. Elevated reticulocyte counts are seen in acquired autoimmune hemolytic anemia, acutely posthemorrhagic anemia, suckle cell anemia, thalassemia major, treatment of iron-deficiency anemia, and treatment of vitamin B12 and folic acid deficiency [20].

A decreased reticulocyte count, or reticulocytopenia, occurs in disease states or conditions in which the bone marrow's ability to respond to hypoxic or anoxic states by an outpouring or reticulocytes has been impaired. Disease states and conditions accompanied by reticulocytopenia are aplastic anemia, aplastic crisis of hemolytic anemia, malignant disorders involving the bone marrow, untreated iron-deficiency anemia, and untreated megaloblastic anemia. Reticulocytopenia also occurs in patients receiving antineoplastic chemotherapeutic agents that cause bone marrow suppression. C-Reactive protein produced in the liver is classified as an acute phase reactant, which means that its levels will rise in response to inflammation in the body. It is also considered to be associated with an increased risk of heart attacks. Bacterial infections will result in a high level [20].

There are a wide variety of measurements of coagulation function. Some of the most common are discussed here. The nursing history and assessment of these patients should include patterns of bleeding. The sequence of basic steps in the coagulation process is: prothrombin, thrombin, fibrinogen, and fibrin [20].

The platelet count measures the number of circulating platelets, or thrombocytes, per mcL of whole blood. Platelet values may be altered by many of the disorders of the blood and blood forming organs. Thrombocytosis, or an elevation in the number of platelets, can be present in acute blood loss, chronic granulocytic leukemia, idiopathic thrombocytopenic purpura, iron-deficiency anemia, and polycythemia vera. Thrombocytopenia, or decreased platelet numbers, may accompany acute granulocytic leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, monomythic leukemia, monocytes leukemia, multiple myeloma, pernicious anemia, idiopathic thrombocytopenic purpura, and aplastic anemia. A drop in the platelet count requires the nurse to implement bleeding precautions. Aspirin is contraindicated [20].

Platelets are usually reported as adequate, low adequate, or high adequate. In some of the hematologic disorders, such as leukemia or idiopathic thrombocytopenic purpura, a quantitative platelet determination is performed. This test is a more accurate determination of the platelet level. Quantitative platelets are reported as specific numbers such as 50,000, 150,000, or 300,000. The normal quantitative platelet range is 150,000–400,000/mcL [20].

The bleeding time, a test that records the duration of active bleeding, provides information on vascular response to injury and helps to evaluate platelet function. The two principal methods of performing the bleeding time are Duke and IVY methods. In the Duke method, bleeding time is measured by observing active bleeding after a puncture on one of the patient's ear lobes. The IVY method, preferred because it is less liable to variation among testers, measures the bleeding time after two small punctures on the patient's forearm. Pressure is applied by inflating a blood pressure cuff up to 40 mm Hg. The patient's bleeding time may be prolonged in any of the leukemias, aplastic anemia, disseminated intravascular coagulation (DIC), idiopathic thrombocytopenic purpura, infectious mononucleosis, multiple myeloma, and pernicious anemia. Bleeding time is also used in the diagnosis of von Willebrand disease [20].

Prothrombin time (PT) evaluates stages II and III in the coagulation cascade. An increased PT may be present in the acute leukemias, DIC, factor VII or X deficiency, polycythemia vera, and multiple myeloma. This test is also used to regulate warfarin therapy [20].

The partial thromboplastin time (PTT) is a general evaluation of the entire coagulation system except for factors VII, XIII, and platelets and can also be used to regulate heparin therapy. A prolonged PTT can occur in DIC and in deficiencies of factors V, VIII, IX, X, XI or XII [20].

The coagulation factors assay or profile is a combination of selected coagulation studies that assists in evaluating all the stages in the clotting cascade and helps to pinpoint the area in which the clotting deficiency or problem occurs. Institutions vary in what is included in a coagulation profile, but a typical profile might contain bleeding time, platelet count, clot retraction, atrial thromboplastin time, and prothrombin time [20].

Factor VIII^AHF (antihemophilic factor) activity is the test for classic hemophilia or hemophilia A. Patients with little or no factor VIII are classified as severe hemophiliacs; those with 1% to 5% of normal values are called moderate hemophiliacs; and those with values between 6% and 30% of the normal are termed mild hemophiliacs. Patients with von Willebrand disease have deficiencies in both factor VIII^AHF and factor VIII^VWF (von Willebrand factor). Deficiency of factor VIIIVFW may range anywhere from 0% to 50% of normal [20].

Other disease processes or changes in health status may interfere with the amount of available factor VIII for normal coagulation. Childbirth, penicillin allergy, and certain antibodies in the blood may interfere with factor VIII activity. Disease processes that inhibit factor VIII activity include lupus erythematosus, multiple myeloma, rheumatoid arthritis, and cancer [20].

Immunoglobulin studies evaluate the amount and types of immunoglobulin (e.g., IgG, IgA, IgM, IgD, IgE) present in the patient. A sample of blood is collected and examined under immunoelectrophoresis. Each immunoglobulin has its own unique pattern. Abnormal levels occur in many hemiplegic disorders. Any immunizations or vaccinations that the patient may have received within the previous 6 months may affect the results. These should be documented and reported to the laboratory; testing may need to be delayed [21].

Serum ferritin determinations evaluate the amount of iron stored in body tissues. Deleted iron supplies depress the synthesis of ferritin. Patients experiencing iron deficiency states, such as iron-deficiency anemia, have decreased serum ferritin levels. The test helps to distinguish between iron-deficiency anemia and anemias associated with chronic disease [20].

Total iron-binding capacity (TIBC) measures the amount of available transferrin (a protein that binds with iron the transports it throughout the body) in the blood. TIBC increases as iron levels and iron stores decrease. Elevated TIBC is found in iron deficiency states, infancy, pregnancy, and blood loss. Decreased TIBC is found in iron overload states such as hemochromatosis, chronic hemolytic anemias (e.g., pernicious anemias), and blood transfusing overload [20].

The sickle cell solubility test screens the presence of hemoglobin S (HbS) in the patient suspected of having sickle cell disease or the patient suspected of being a carrier of the sickle cell trait. The patient with sickle cell disease has 90% or greater HbS. Individuals with 50% or less HbS are known carriers of the disease; the remainder of their hemoglobin is the normal adult hemoglobin (HbA). Normally, the erythrocyte contains no HbS. Crescent-shaped erythrocytes are termed sickle cells [22].

Bone marrow examination is performed using two complementary techniques: aspiration and biopsy. Bone marrow aspiration removes liquid marrow by suction, allowing for evaluation of cell morphology, blast counts, and cytogenetic analysis. In contrast, bone marrow biopsy provides an intact core sample, enabling assessment of overall marrow architecture, cellularity, and the relationship of hematopoietic cells to stromal elements. Because each method yields unique but complementary information, both are generally required for accurate diagnosis. Peripheral blood smears and cytogenetic studies further supplement the evaluation, ensuring a comprehensive assessment of hematologic disorders [23x].

Adequate sampling is critical to avoid repeat procedures and to ensure diagnostic accuracy. Aspiration samples should contain spicules, which confirm entry into the marrow cavity. Biopsy specimens should measure at least 1.5–2 cm and include a sufficient number of preserved intertrabecular areas. In cases where aspiration is unsuccessful, such as in fibrotic or densely packed marrow, touch preparations from core biopsies can be used. Two biopsy cores are generally recommended to maximize diagnostic yield and to avoid missing focal abnormalities, such as blast clusters seen in aggressive myelodysplastic syndromes [2,3].

Before the procedure, patients must be carefully evaluated for bleeding risk, anesthetic allergies, and anxiety, as bone marrow aspiration and biopsy are painful for most patients. Patient education is vital, as inadequate information can increase anxiety and perceived pain. Analgesia with local lidocaine is standard, while sedation may be required in highly anxious individuals, though it carries additional risks and logistical challenges. Site selection also plays a role in safety and comfort; the posterior iliac crest is the preferred site in adults, while the sternum is used only for aspiration in special circumstances. Imaging techniques such as ultrasound or fluoroscopy may assist in site localization, particularly in obese patients [2,3].

The procedures require specialized needles and equipment, with both single-needle and two-needle techniques in practice. Samples are immediately processed to prepare smears, squash slides, and material for cytogenetic and molecular testing. Following aspiration or biopsy, firm pressure is applied to prevent bleeding, and patients are monitored for signs of infection or persistent pain. Complications are uncommon but can include hemorrhage, infection, or trauma to surrounding structures. Careful technique, adequate patient preparation, and post-procedural monitoring help minimize risks and ensure optimal diagnostic value from the procedure.

The four basic phenotypes of typing are O, A, B, and AB (Table 1) [28,29,30]. Antibodies are produced by the immune system against whichever ABO blood group antigens are not found in an individual's red blood cells. These antibodies are formed naturally; however, they can also be formed after many transfusions have occurred [28,29,30].

Rhesus (Rh) is another antigen occasionally found within red blood cells. If the antigen is identified, then the person is said to be Rh positive (+). If the Rh antigen is not identified, the individual is Rh negative (-).

The Rh system includes more than 50 red cell antigens, but the five main antigens are D, C, c, E, and e [31,32,33]. The D antigen is the most significant antigen in the Rh typing system. If the D antigen is present, the individual is considered Rh+; if it is absent, the individual is Rh-. It is particularly important to avoid transfusing Rh+ red blood cells into Rh- girls and women during pregnancy or childbirth because anti-D-related hemolytic disease of fetus and newborn can result in mild-to-severe anemia and even death of the Rh+ fetus and/or newborn [33,34].

While blood product transfusion is one of the most common procedures, it is not risk free. An antibody identification test is performed to identify the presence of any unexpected allo- or autoantibodies. This test is typically done when an atypical antibody is identified though the antibody screening during the blood typing process [30,34,35,36].

The development of alloantibodies can occur related to RBC transfusions. Just as with child-bearing women, alloantibodies may be significant in future transfusion situations, resulting in acute or delayed hemolytic transfusion reactions. There could also be significant difficulty locating compatible RBC units for future blood transfusions [34,37].

Crossmatching is the process of verifying the compatibility between the donor and recipient of the blood product. This is the final step in procurement of RBCs appropriate for transfusion. Crossmatching has two parts: major crossmatching, which involves the recipient's plasma with the donor RBCs, and minor crossmatch, during which donor plasma is mixed with recipient RBCs [38].

This process involves performing a saline wash of the RBCs and plasma of both the recipient and donor blood per the major and minor crossmatch processes. Anti-human globulin (AHG) is then added to the vial, allowed to rest for five minutes, then spun in the centrifuge. If agglutination occurs (the clumping of RBCs within the solution), the donor and recipient are not compatible, and the process needs to be restarted. If no agglutination occurs, the test is positive for compatibility [39].

Major crossmatch is the most important of the crossmatching process, allowing for safe blood transfusion. The minor crossmatch is less important as the donor antibodies will be swiftly diluted within the recipient of the blood product. However, should the minor test be incompatible, it is strongly suggested that transfusion be avoided [38,39].

RBCs are blood cells made in the bone marrow and contain the protein hemoglobin, which carries oxygen (O₂) [42,43]. RBCs transport and remove carbon dioxide (CO₂) in the venous return to the lungs to be exhaled. RBCs are also involved in tissue protection and regulation of cardiovascular homeostasis [43]. The normal RBC count is 4.3–5.9 million cells/mm³ in men and 3.5–5.5 million cells/mm³ in women [44].

Blood plasma is made up of mostly water and soluble proteins, lipoproteins, and extracellular vesicles [10mf]. Plasma carries platelets, RBCs, and WBCs throughout the body and makes up approximately 55% of the blood. It contains antibodies or immunoglobulins, which help protect against infection [45]. Plasma contains coagulants to aid in blood clotting; albumin and globulin to aide in colloidal osmotic pressure; and electrolytes to maintain the pH of the blood [46].

Plasma transfusions may be administered for symptomatic anemia, acute sickle cell crisis, and acute blood loss of more than 30% of blood volume. Plasma transfusions are considered first-line replacement fluid in the treatment of conditions such as thrombotic thrombocytopenic purpura. It is not recommended to use plasma transfusions to correct mild coagulation abnormalities in the absence of bleeding such as prior to a surgical procedure [47].

Platelets, also termed thrombocytes, are also produced by the bone marrow [48]. The normal platelet reference range is 150,000–400,000 cells/mm³ regardless of gender. Platelets are an integral part of the clotting cascade [49].

Platelet transfusions can be administered to individuals to prevent bleeding with platelet counts less than reference range, prior to medical procedures with shared decision making, and to treat bleeding associated with thrombocytopenia or platelet dysfunction [50].

Cryoprecipitate is derived from plasma and contains fibrinogen, factor VIII, von Willebrand factor, factor XIII, and fibronectin. It is used for immediate blood loss or can be directly prior to procedures in which patients have hypofibrinogenemia [54]. Conditions that are potential indications for cryoprecipitate transfusion include [51,52,53]:

Granulocytes are a part of the immune system. The most common type is neutrophils, and granulocyte transfusion may be indicated in the treatment of neutropenia. There are ongoing trials assessing the safety and efficacy of granulocyte transfusion [55].

For a blood product to be administered, specific equipment is needed [56,57,58]:

It is imperative to inspect all equipment for integrity and expiration dates and remove items if they have been compromised or have expired. Hand hygiene is performed multiple times throughout this procedure along with appropriate donning and doffing of gloves [56,57,58].

The first step is to obtain informed consent from the patient or the caregiver. This should be done prior to the order being placed. The clinician ordering the blood products should provide the patient or the caregiver with a description of risks, benefits, and treatment alternatives. The provider should provide ample time for the patient and/or caregiver to ask questions. This ensures an understanding of the practice but also the opportunity to accept or refuse the transfusion. The clinician should also discuss any personal, religious, or cultural beliefs potentially affecting blood product transfusions. The elements of the transfusion should be discussed, from compatibility testing of the blood to the signs and symptoms of possible reactions. This informed consent should be signed by the patient or the caregiver and kept within the electronic medical record. Health literacy can be assessed during this discussion as well.

Verify the patient with at minimum two patient identifiers according to facility policy. These identifiers should be compared with the patient's wrist band and electronic medical record.

Verify the order. This should confirm the indication for the transfusion, the date, time to transfuse (as certain patient populations require longer transfusion times), special instructions (e.g., irradiated or leukocyte-depleted blood), or any pre- or post-transfusion medications. If more than one blood product component is to be transfused, the specified order of transfusion should be indicated within the order as well.

It is important to choose the appropriate venous access device based on the condition of the patient and the transfusion needs. A peripheral intravenous catheter (PIVC) can be used for blood products. For proper flow ideally 18-, 20-, or 22-gauge catheters should be used. If a small-gauge PIVC (e.g., 24-gauge) is used, the flow rate should be adjusted as the smaller gauge catheter can cause hemolysis of the product. Infants or children can utilize 22- to 24-gauge PIVCs or an umbilical catheter. Central venous access devices (CVADs) (e.g., central line, implantable port) may be used if available, when multiple infusions will be necessary, or if peripheral venous access is not possible. Intraouseus infusion is an option if PIVC or CVAD is not available and the patient is in an unstable condition.

During infusion of blood or blood products, no medications can be administered through the same infusion line. It is generally in the best interest of the patient to have two access sites: one for the blood product and the other for any potential medications.

Verify that all pre-transfusion testing has been completed along with assessing the patient's history for any prior transfusions and transfusion reactions. Blood sample testing for crossmatching products should be sampled within 72 hours of the transfusion and resampled after 72 hours.

Obtain pre-infusion vital signs, including temperature, pulse, respirations, and blood pressure, within 30 minutes of administering the blood product. In addition to vital signs, the re-infusion assessment should include respiratory assessment, skin (evidence of rash), documentation of conditions that may increase the risk of transfusion-related adverse reactions (e.g., current fever, heart failure, renal disease, fluid volume excess), an appropriate and patent vascular access device, and current laboratory values.

Obtain the blood products from the laboratory, blood bank, or transfusion services department. The process to obtain blood products is organization-specific, and the facilities procedures should be followed. After the blood is obtained, the nurse should inspect the product for the correct product ordered, expiration date, ABO group and Rh type of both the donor and recipient, and date/time the blood was issued. There is a four-hour window from the time the blood is released from the blood bank to completion of transfusion, which is why it is important to only obtain the blood products to be transfused once all equipment is available and ready to be used. The blood product should be handled with gloves and should be examined for any leaks, abnormal color, clots, excessive air, or unusual odor. Any expired or abnormal appearing/smelling blood should be returned to the blood bank as soon as possible.

At the bedside, two nurses qualified to administer the blood products should be present to provide another verification process to match the patient to the blood ordered by the provider and to the blood product received. Information to verify includes:

After checking all identifying information, the two nurses will sign the transfusion form to indicate that the identification was correct. Some systems have electronic signature options.

The Y-tubing is now ready to be spiked with the 0.9% normal saline (NS) first, then the blood. Ensure all clamps are closed prior to spiking both the normal saline and the blood. Hang the bag on the IV pole and prime the tubing. Then, open the upper clamp on the NS side of tubing and squeeze the drip chamber until fluid covers the filter and one-third to one-half of the drip chamber. When this is complete, the blood components can be prepared for administration. Ensure the NS clamp is closed above filter, and gently invert the bag two or three times, turning back and forth. Remove the protective covering from the access port, and spike the blood component unit with the second Y-connector. It is then safe to open the clamp above the filter to the blood unit, and prime the tubing with blood/blood product. Blood will flow into the drip chamber. Tap the filter chamber to remove any residual air. Close the clamp when the tubing is filled, and apply a cap to the end of the tubing to maintain an aseptic system. When ready to attach the common tubing to the patient's VAD, remove the cap and attach the primed tubing to patient's VAD after first cleansing the catheter hub with an antiseptic swab. The NS-primed blood administration tubing can then be directly attached to patient's VAD.

The blood product is now ready to be infused. The infusion can be completed by drip (gtt) counts or by utilizing an infusion pump specifically labeled for blood transfusion. Using the gtt method, open the common tubing clamp and the clamp to blood bag, the regulate blood infusion to allow only 2 mL/minute to infuse in the initial 15 minutes. The nurse must remain with the patient during this period to monitor and assess the patient. Initial flow rate during this time should be 1–2 mL/minute or 10–20 gtt/minute. For administration using the electronic infusion device (EID), insert the primed infusion tubing into chamber of the control mechanism of the EID, with a roller clamp on the common IV tubing between the EID and the patient. The tubing through an "air in line" alarm system (equipped on most EIDs). Finally, close the door, turn on the power, and select the required blood administration rate or blood transfusion program.

The patient's vital signs should be checked within the first 15 minutes of the transfusion being initiated, upon completion of the transfusion, and one hour post-transfusion. The infusion site (whether PIVC or CVAD) should be monitored and documented at the same time that vitals are taken. (Nurses should adhere to their facility's policy for vital assessment timing during transfusion). Assess vital signs and visually check on the patient for any adverse reactions at least every 30 minutes throughout the transfusion. Upon identification of any change in the patient's condition, vital signs should be checked immediately. After the first 15 minutes have passed safely without compromise, the rate can be increased to the provider's orders and to ensure the product can be infused within the four-hour window. Of note, while blood products can typically be infused over a maximum of four hours, platelets are infused over one to two hours and plasma over 15 to 60 minutes. Cyro is transfused as rapidly as tolerated.

After blood has infused, turn off the EID and clamp the blood bag. Remove the tubing from the EID, and clear the transfusion line with NS by opening the clamp to the NS bag and infusing slowly. Discard the blood bag according to organization policy. When consecutive units are ordered, maintain line patency with NS at a "to keep vein open" (KVO) rate as ordered by the physician and retrieve subsequent unit for administration. At the four-hour mark, if the blood has not fully transfused, the infusion should be stopped and tubing removed without clearing the line. For patients who are to receive more than one blood product, if the first unit requires four hours for transfusion, the administration set and filter are not reused.

To reiterate, the documentation of any blood component administration should include the following:

Perfluorochemicals are synthetic compounds that dissolve 40% to 60% oxygen per unit volume, approximately three times the capacity of blood, and also have a carbon-dioxide-carrying capacity three times greater than their ability to carry oxygen [61,62]. In their pure form, perfluorochemicals cannot act in the body unless they are emulsified, allowing for diffusion into cells and capillaries. In emulsion, larger particles are excreted more quickly (6 days) than smaller particles (up to 900 days). The process of emulsification and the size of articles is important because articles not excreted tend to aggregate in the liver and spleen [61,62].

Although these agents have theoretical efficacy, supported by some positive studies, issues with manufacturing and development have led them to become mostly discontinued.

The first generation of hemoglobin-based blood substitutes were stroma-free hemoglobin, which uses human hemoglobin stripped of the elements that clog capillaries. The substance has several advantages over other synthetic blood products: it functions at low levels of oxygen, it has a colloidal osmotic effect and thus works as a plasma expander, it has universal compatibility and it can be stored indefinitely. Stroma-free hemoglobin also has several disadvantages: it can only be obtained from human donors; when it is metabolized, iron accumulates and iron toxicity develops; it will not solve problems related to agents that are toxic to hemoglobin (carbon monoxide) because it will most likely be affected as well; and because it is a volume expander, the patient with anemia who has an adequate circulating blood volume but a poor hemoglobin value must be monitored carefully for fluid overload [63].

To help address these disadvantages, pyridoxilated hemoglobin-polyoxyethylene conjugates (PHPCs) have been prepared through chemical modification of SFH. These second-generation hemoglobin-based blood substitutes prevent the major disadvantages of stroma-free hemoglobin products, specifically increased O₂ affinity, short circulatory half-life, and nephrotoxicity.

PEGylated hemoglobin is derived from either human or bovine sources and is modified with maleimide or carboxylated to produce a hemoglobin with unique O₂ transport functions. These products may be beneficial to preventing or treating ischemia-related morbidity; clinical trials are underway.

There are three main types of sickle cell disease defined by the specific genetic combination [65]. The most severe form is HbSS, commonly referred to as sickle cell disease. Patients with this type have inherited one sickle cell gene from each parent. Persons who have inherited a sickle cell gene from one parent and a gene for abnormal hemoglobin from the other parent have the HbSC type. This is usually a milder form of sickle cell disease. The final type is HbS beta thalassemia, which is characterized by inheritance of a sickle cell gene from one parent and a gene for beta thalassemia, another type of anemia, from the other parent. There are two types of beta thalassemia: "zero" (HbS beta0) and "plus" (HbS beta+). Those with HbS beta0-thalassemia usually have a severe form of sickle cell disease, while those with HbS beta+ tend to have a milder form [65].

Even more prevalent than sickle cell disease is sickle cell trait. This condition is present in persons who inherit a sickle cell gene from one parent and a normal gene from the other parent. The ratio of infant carriers of hemoglobin variant traits to infants with sickle cell disease is approximately 50:1 [68]. Those with sickle cell trait are usually asymptomatic and live a normal life, but they can pass the trait on to their children.

Pain is the primary reason that medical care is sought by persons with sickle cell disease, usually during an acute pain crisis. Acute pain crises are commonly triggered by dehydration, infection, stress, and changes in body temperature and unfold in four distinct phases [64]:

In patients with sickle cell disease experiencing pain crises, the lower back, knee/shin area, and hips are the sites most often affected. A higher number of pain sites are found in patients with depression and in those 45 years of age and older [69].

A single nucleotide mutation is the underlying basis of sickle cell disease. It involves alteration of the glutamate for valine in the sixth position of the beta-globin protein, which predisposes hemoglobin to polymerize when deoxygenated, causing red blood cells to assume the characteristic sickle shape. This red blood cell deoxygenation and sickling accounts for sickle cell disease characteristics of anemia, hemolysis, and acute and chronic complications from vascular occlusion that affect multiple organs [70]. The deformed red blood cells tend to clump together to increase blood viscosity, leading to microvascular blockage and ischemia. Pain during an acute crisis is due to ischemic occlusion of the microcirculation from red blood cell aggregation and resultant decreased blood flow to distal tissues. The most common cause of recurrent pain episodes is vaso-occlusion of the microcirculation and destruction of bones, joints, and visceral organs [71]. Chronic pain can occur from complications of sickle cell disease such as avascular necrosis or ankle ulcers superimposed on acute sickle cell pain. Additionally, frequent episodes of acute pain in sickle cell disease can resemble chronic pain [71].

Chronic sickle cell disease pain involves modulation of the afferent nociceptive pathways in the spinal cord (such as the spinothalamic tract) that transmit pain from the periphery to the brain for processing [64]. Neuropathic pain is uncommon [65]. Chronic pain from sickle cell disease can be physically and psychologically debilitating; consistent with chronic pain from other conditions, chronic sickle cell disease pain involves sensation, emotion, cognition, memory, and context [65].

The most common chronic pain syndromes in sickle cell disease include [65]:

No single treatment is effective for all people with sickle cell disease; instead, appropriate treatment options are determined according to symptom severity [65]. Nonpharmacologic prevention includes avoiding dehydration, extreme temperatures, high altitudes (including flying), and low oxygen levels from intense exercise or athletic training [65,72].

For prevention of acute pain episodes, hydroxyurea is most often used [66]. This agent acts by ribonucleotide inhibition and induction of fetal hemoglobin, which possesses superior affinity for oxygen binding. It is FDA-approved for use in adults and children 2 years of age and older and is the only treatment for sickle cell disease that modifies the disease process. Hydroxyurea is effective in reducing pain crises, painful symptoms, need for blood transfusion, and mortality. As such, it represents the backbone of sickle cell disease management. The usual daily oral dose is 15–35 mg/kg [66,73]. Inconsistent adherence reduces its efficacy, and patient adherence can be challenged by the three- to six-month delay between treatment initiation and the onset of clinical response. More frequent follow-up contact with support and encouragement may be needed in some patients.

For adults and children with sickle cell disease presenting to an acute care setting with acute pain related to sickle cell disease, the American Society of Hematology guideline panel recommends rapid (within one hour of emergency department arrival) assessment and administration of analgesia with frequent reassessments (every 30 to 60 minutes) to optimize pain control.

(https://ashpublications.org/bloodadvances/article/4/12/2656/460974 Last Accessed: September 29, 2025)

Strength of Recommendation/Level of Evidence: Strong recommendation based on low certainty in the evidence about effects

Management of acute pain episodes may include intravenous fluids, pain-reducing medication or hospitalization (for severe pain crises). Management typically requires stronger analgesic agents, with codeine and tramadol useful for moderate pain and morphine, oxycodone, hydrocodone, and hydromorphone more effective in treating severe and breakthrough pain [65]. For first-time opioid therapy for severe pain, the use of morphine sulfate or hydromorphone is favored. With recurrent pain, the best initial choice of opioid and dose for severe sickle cell pain is that which previously provided adequate analgesia. Intravenous administration is recommended in severe pain. Patients and clinicians may prefer a 5–10 mg loading dose of parenteral morphine or equivalent [65].

L-glutamine (Endari) is approved for patients 5 years of age and older to reduce acute complications of sickle cell disease [73,74]. Taking L-glutamine may lead to fewer hospital admissions, fewer pain crises, less need for blood transfusions, and a lower risk of acute chest syndrome. L-glutamine comes in powder form that should be mixed with cold or room temperature drink or food (e.g., water, milk, apple juice, applesauce). Side effects may include nausea, fatigue, chest pain, and pain in bones or muscles [73,74].

Crizanlizumab-tmca (Adakveo) is a humanized monoclonal antibody that inhibits interactions between endothelial cells, platelets, red blood cells, and leukocytes, which may result in decreased platelet aggregation, maintenance of blood flow, and minimized sickle cell-related pain crises. It is approved for adults and children 16 years of age and older to reduce the frequency of vaso-occlusive crises. Crizanlizumab-tmca is administered IV at an initial dose of 5 mg/kg once every two weeks for two doses, followed by 5 mg/kg once every four weeks thereafter. It may be administered with or without hydroxyurea [73,74].

Voxelotor (Oxbryta) received approval for the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older in 2019 with an expansion to patients aged 4 to 11 in 2021 under the FDA's Accelerated Approval Program. This was based on data from the phase 3 HOPE trial and phase 2 HOPE-KIDS trial. In postmarketing clinical studies in patients with sickle cell disease, higher rates of vaso-occlusive crises and fatal events were reported with voxelotor (compared to placebo) [73,75,76]. In September 2024, the manufacturer announced a voluntary withdrawal of voxelotor and a discontinuation of all active clinical trials and expanded access programs. The decision was based on clinical data that indicates the benefit of the drug does not outweigh the risks for the sickle cell patient population [75,76].

Adjunctive medications may also be indicated. Parenteral NSAIDs can reduce opioid requirements and provide greater ease in transition to oral analgesics [64]. Parenteral corticosteroids can be beneficial during crisis phases, but efficacy data beyond the initial 48 hours is lacking.

Intraspinal analgesics should be considered only with insufficient response to maximum-dose systemic opioids and adjuvant medications. Epidural anesthetics alone or with fentanyl can be effective in acute refractory pain [64].

For chronic pain associated with sickle cell disease, long-acting and short-acting opioids, NSAIDs and acetaminophen, and adjuvant medications form the basis of long-term management [64]. Aspirin should be avoided due to the risk of Reye syndrome. Codeine, low-dose oxycodone, or low-dose hydrocodone are preferred for treatment of moderate chronic pain.

In patients requiring chronic opioid therapy, extended-release, sustained-release, or long-half-life opioid formulations are favored because of ease in administration and more consistent analgesia. Specifically, transdermal fentanyl is effective for chronic pain management in patients who are opioid tolerant. Short-acting opioids may be used for rescue dosing early in the treatment regimen, for acute episodes of breakthrough pain or for analgesic bridge until steady-state is achieved with a long-acting formulation [65].

Adjunctive therapy with SNRIs and TCAs can alter pain perception in the spinothalamic tract. Blood transfusion may be necessary for severe anemia. Common antecedents for transfusion necessity include sudden worsening of anemia due to infection and splenomegaly [65,72].

Massage therapy may be effective as a therapy adjunct. Participants in one trial reported significant decreases in pain intensity following massage with a mean pain scale score of 9.6 before massage versus 2.8 after massage [77].

Transplantation is the only known cure for sickle cell disease and involves blood or bone marrow stem cell transplantation. To prevent potentially severe complications, donor-recipient stem cells should be closely matched using human leukocyte antigen (HLA) tissue typing. Unfortunately, only a small number of patients with sickle cell disease are appropriate candidates for stem cell transplantation [72].

The symptoms of thalassemia are caused by anemia. More severe cases may be associated with:

Treatment of thalassemia consists of blood transfusions, iron chelation therapy, folic acid supplements, and bone marrow and stem cell transplant, depending on the type of thalassemia diagnosed [78]. Some will require splenectomy.

The types of symptoms experienced, and their intensity, may vary among people with this disease. The most frequent symptoms are anemia, increased red cell osmotic fragility, spontaneous hemolytic crises, splenomegaly, spherocytosis, reticulocytosis, pallor, muscle weakness, jaundice, increased mean corpuscular hemoglobin concentration (>27–31 picograms/cell), hypofibrinogenemia, hypercoagulability, hepatomegaly, and cholelithiasis.

Splenectomy is recommended for all patients diagnosed with hereditary spherocytosis. The procedure does not correct the erythrocyte defect but rather removes the major organ responsible for the destruction and removal of the spherocytes from the circulation, avoiding dramatic decreases in RBCs. The rationale for splenectomy is the inability to predict which patient will undergo spontaneous, life-threatening crises. For those with little or no anemia, the risk of surgery may seem too great. Splenectomy is a relatively safe procedure for patients older than 4 years of age [81]. In addition, folate supplementation is recommended in severe and moderate HS but is not necessary in mild HS [82].

Splenectomy is associated with a lifelong increased risk of overwhelming infection, particularly with pneumococcal species, which is not completely eliminated by pre-operative vaccinations and post-splenectomy antibiotic prophylaxis [82]. Vaccination is strongly recommended, and patients and/or their caregivers should be counselled regarding the need to avoid infection and practice good hygiene.

The most frequent manifestation of a hemolytic episode of G-6-PD deficiency is anemia. The patient may become pale and, in severe hemolysis, have shortness of breath and abdominal or back pain. The urine may turn dark and even black [84].

The laboratory diagnosis of G-6-PD deficiency is made by a simple blood test to determine the level of G-6-PD. The normal value varies according to the actual laboratory procedure used, but usually G-6-PD is present in substantial amounts. Individuals with levels below is considered normal for that laboratory are considered G-6-PD deficient [84].

Because most episodes of hemolysis are self-limiting, no intervention is usually necessary. No specific drug therapy is indicated for G-6-PD deficiency, but patients should avoid certain drugs, including analgesics, ascorbic acid (vitamin C), naphthalene, methylene blue, and phenylhydrazine. Patients should avoid ingestion of fava beans. If hemolysis is severe, transfusion therapy with packed RBCs may be administered [85,86].

The nursing management of the patient with G-6-PD deficiency consists of providing information on the disease process, including stimuli imitating a hemolytic episode and signs and symptoms indicating hemolysis. Send a list of agents causing hemolysis home with patients and encourage them to read labels to all over-the-counter drugs to avoid the accidental ingestion of these compounds [2].

Clinical manifestations of severe factor VIII or IX deficiency may be detected during the neonatal period following circumcision. Milder forms of hemophilia may not be detected until childhood or adolescence, when prolonged bleeding follows a tooth extraction. The most common clinical manifestation is hemarthrosis (bleeding into the joint) in the knee; however, the hip, ankle, shoulder, elbow, and wrist also can be affected. The patient frequently has a history of only mild trauma to the involved joint, which becomes painful, swollen, tender, and stiff. Later complications of hemarthrosis include loss of joint motion, contracture formation, muscle atrophy, and joint degeneration and deformity [88,89].

Hematomas may form with only slight trauma. Bleeding, most commonly subcutaneous or intramuscular, primarily involves the lower extremities. Enough blood may be lost into a thigh to cause symptoms of shock. Petechiae do not accompany ecchymotic areas. Other manifestations of hemorrhages include epistaxis, hematuria, swelling of the tongue (from accidentally biting it while easting), paresthesia (from pressure on a nerve by bleeding into tissues), and ischemia (form pressure on blood vessels). The most life-threatening complication of hemophilia is intracranial hemorrhage. Superficial cuts usually do not cause undue problems [88,89].

Hemophilia is diagnosed by laboratory serum determinations. Tests include serum calcium, prothrombin time (PT)), partial thromboplastin time (PTT), quantitative platelets, coagulation factors assay, and antibody directed against factor VIII (for hemophilia A). Serum calcium level, PT, and platelet count are normal in hemophilia, and PTT is prolonged.

The major emphasis is on the patient avoiding all drugs that increase bleeding time. Because many over-the-counter preparations contain aspirin or aspirin products, encourage patients to read medication labels before ingestion. Ideally, the patient would avoid all over-the-counter preparations to avoid accidental aspirin ingestion [89].

The maintenance or promotion of optimal nutritional status ensures good dental hygiene. Because hemophiliacs bleed excessively after dental extractions, preventing dental cavities and ultimately, tooth extraction is the goal of nutritional management [89].

Administration of the appropriate factor concentrate is an important treatment measure prophylactically as well as during episodes of acute bleeding. In individuals with severe and moderately severe hemophilia prophylaxis is recommended over episodic treatment of bleeding events [90].

Nursing management during an acute bleeding episode involves the IV administration of the deficient factor—either factor VIII^AHF human or factor IX human. With joint pain and hemarthrosis, splinting or casting the involved joint may be indicated. Whenever a patient with hemophilia is admitted to the hospital, nursing assessments are directed toward the prompt recognition of hemorrhage [3].

As in hemophilia, abnormal bleeding in von Willebrand disease begins in early childhood. Epistaxis and ecchymosis are common, whereas petechiae are not. Fatal bleeding episodes occur but are extremely rare. The hemarthrosis in von Willebrand disease differs from that in hemophilia. Hemarthrosis is not common in von Willebrand disease, and joint damage is not permanent. In contrast, hemarthrosis is common in hemophilia. Hemophiliac patients have repeated episodes of hemarthrosis involving the same joint, whereas von Willebrand patients do not. Although excessive bleeding following surgery can be a problem, it can be managed with the infusion of factor VIII concentrate. Von Willebrand disease decreases in severity as the patient ages; hemophilia does not [87].

Major therapies include use of desmopressin to induce endothelial release of stored von Willebrand factor (VWF) and factor VIII (FVIII) and use of VWF concentrates, including both plasma-derived and recombinant products, as well as adjuvant therapies, such as antifibrinolytic tranexamic acid. In 2025, the U.S. Food and Drug Administration approved expanded use of von Willebrand factor (Recombinant) (Vonvendi) for routine prophylactic use in adults 18 years of age and older with all types of von Willebrand disease and on-demand and treatment of bleeding episodes and perioperative use in children with von Willebrand disease [91].

Encourage the patient to avoid bleeding episodes as much as possible and to read labels on all medications and to avoid all over-the-counter preparations, if possible. All medications that interfere with bleeding time, such as aspirin, should be avoided [87].

Clinical manifestations of aplastic anemia are related to the pancytopenia. Patients have symptoms of severe bone marrow depression: pallor, tiredness, repeated infections, malaise, and bleeding tendencies. Bleeding tendencies may be occult or conspicuous; major or minor, such as gastrointestinal bleeding versus gingival oozing; or in the form of purpura or petechiae. Hepatosplenomegaly is usually not present at diagnosis. Diagnosis made by bone marrow aspiration, bone marrow biopsy, or both. The bone marrow is found to contain primarily hypocellular fatty deposits [94].

The goal of treatment of aplastic anemia is to control symptoms and prevent complications. Initial treatment includes blood and platelet transfusions and IV antibiotics. While immunosuppressive drugs are effective in treating aplastic anemia, these medications further weaken the immune response, leaving the patient at risk of complications. ESAs and colony-stimulating factors are also used [92]. For severe cases, an allogeneic bone marrow transplant may be advised. However, it is important to note that elderly patients may be unable to tolerate the preparation for transplant and are at an increased risk for complications. If left untreated, death will usually occur rapidly.

Because of vitamin B12 therapy, the classic clinical manifestation of pernicious anemia is rare today. However, because vitamin B12 has such profound effects on hematopoiesis and the normal structure and function of the nervous system, a review of these manifestations is warranted [96].

The onset of pernicious anemia or hemolytic anemia occurs in late middle adult life. The first clinical manifestations are usually those of anemia. Patients demonstrate pallor with slight icterus, as well as lassitude and weakness disproportionate to the degree of existing anemia and a beefy red tongue also occurs. Most red cell indices of the peripheral blood count are abnormal. Quantitative erythrocyte counts may be as low as 2 million/mcL; the hemoglobin level is approximately 8 g/dL; and mean corpuscular volume (MCV) is elevated. Only the mean corpuscular hemoglobin count (MCHC) is normal. The peripheral blood smear demonstrates anisocytosis and poikilocytosis. These changes demonstrate the impact of vitamin B12 on normal erythrocyte maturation. A hemoglobin level of 15 indicates improvement [96].

Neurologic manifestations of pernicious anemia also show the important role of vitamin B12 on nerve structure and subsequent nerve function. Demyelination of nerves and degeneration of white matter occur in vitamin B12 deficient states. The loss of vibratory sense may be the first clue in the diagnosis of pernicious anemia. Numbness and tingling of the extremities can follow. As demyelination and degeneration continue, paralysis and psychosis may develop. After neurologic damage has occurred, neurologic function may not be regained [96].

The stomach atrophies and loses its acid and enzyme-secreting abilities, developing achlorhydria and acholia. The remainder of the intestinal tract enlarges, and digestion becomes difficult as the disease progresses [97].

Pernicious anemia is diagnosed by the Schilling test. Gastric analysis may also be used. In addition, multiple laboratory studies are performed on the peripheral blood both before and after the initiation of vitamin B12 therapy. Examination of the bone marrow rules out any other existing hematologic disorders. A through neurologic examination, including a test of vibratory sense should be part of the patient's history and physical examination.

Treatment of pernicious anemia once consisted of daily feedings of raw or rare liver. Later, crude liver extract was developed, but it lost major potency when administered orally. Liver extract was painful when administered IM, stained tissue, and sometimes caused tissue necrosis. Finally, in 1948, the red crystalline factor now known as vitamin, B12 or cyanocobalamin, was discovered. This vitamin has all the antiemetic principles of crude liver extract and is the elusive extrinsic factor. Treatment of pernicious anemia includes regular injections of vitamin B12. Methylcobalamin has also been created and does not contain cyanide. Neuropathy worsens if the medical treatment regimen is not followed [96,97].

Nursing management of pernicious anemia includes patient support and education during the diagnostic phase, patient education about the disease process, the importance of compliance with lifelong vitamin B12 therapy, and assessment and rehabilitation of patients with neurologic changes. The patient with pernicious anemia will need assistance to complete activities of daily living until the lassitude and weakness are resolved. Encourage these patients to rest frequently and make every effort not to tire them by long and vigorous days of testing [3].

After the diagnosis of pernicious anemia and the initiation of vitamin B12 therapy, the patient's hemogram quickly returns to normal. Results of the peripheral blood smear may begin to improve as early as 4 days after the initiation of vitamin therapy. In addition, a dramatically increased sense of well-being accompanies the hematology improvement. The patient with pernicious anemia is committed to a lifetime of vitamin B12 therapy. Noncompliance causes the return of symptoms and possibly more dramatic consequences, such as neurologic involvement. Thus, these patients must understand the rationale for vitamin B12 therapy and comply completely with the chemotherapeutic regimen. Vitamin B12 therapy administered before the onset of neurologic signs and symptoms is ideal. When these signs and symptoms have already appeared, prompt and accurate diagnosis and treatment is imperative. Physical therapy may help restore some use and function, but residual neurologic damage may persist for life [3].

Clinical signs and symptoms of iron-deficiency anemia depend on the condition's severity. The patient feels chronically tired and may be pale. The normal blood level for hemoglobin is 13–15 g/100 mL. The erythrocyte is microcytic and hypochromic. Laboratory studies indicate a hemoglobin level of less than 12 g/dL, decreased serum ferritin levels, increased total iron-binding capacity, and decreased iron stores in the bone marrow. Patients with severe anemia may have malaise, tachycardia, and shortness of breath on exertion. The patient with anemia would have postural hypotension [97].

Pica may develop in some patients with anemia. Pica is a condition whereby the patient has an unusual craving to eat specific non-food item, such as dirt, ice, starch, ashes, or clay. Pica is associated with both mineral deficiency (including iron-deficiency anemia) and mental health conditions. Pagophagia, a craving (pica) for ice, is present in about 50% of patients with iron deficiency, even in the absence of frank anemia [101]. Probing for pica is not part of the routine medical history, but it should be included whenever anemia is suspected or newly diagnosed, as it is a powerful clue to iron deficiency.

The British Society of Gastroenterology recommends the initial treatment of iron-deficiency anemia should be with one tablet per day of ferrous sulphate, fumarate, or gluconate. If not tolerated, a reduced dose of one tablet every other day, alternative oral preparations, or parenteral iron should be considered.

(https://gut.bmj.com/content/70/11/2030.long Last Accessed: September 29, 2025)

Strength of Recommendation/Level of Evidence: Strong recommendation, moderate-quality evidence

Because the major cause of iron deficiency is overt or occult blood loss, the first step should be to identify and treat the source of iron or blood loss, which should improve Hgb levels and symptoms of anemia. Any medications that may be blocking iron absorption should be discontinued. In cases of malnutrition or non-drug-induced impaired gastrointestinal absorption of iron, oral supplementation may be indicated. The recommended oral supplement for the treatment of iron deficiency in older adults has not been established. The adult dosage regimen is usually 325 mg of ferrous sulfate three times per day to provide 150–200 mg/day of elemental iron; however, this regimen is associated with high rates of adverse effects, including black stools, abdominal discomfort, diarrhea, nausea/vomiting, and constipation [100]. one study of patients older than 80 years of age found that daily doses of 15 mg or 50 mg liquid ferrous gluconate or 150 mg ferrous calcium citrate tablets was better tolerated and resulted in similar outcomes, with significant increases in Hgb evidenced in all three treatment groups [102]. Liquid formulations of ferrous sulfate administered in small doses (15 mg) less frequently and with orange juice to facilitate absorption may be more effective and better tolerated [100]. The lowest possible dose should be used first, with gradual titration, if necessary. If a patient is unable to take even the smallest dose of oral iron due to adverse effects (e.g., nausea, constipation, vomiting) or if improvement in Hgb cannot be obtained by oral supplementation (e.g., continued bleeding), parenteral iron therapy may be appropriate. After hemoglobin and serum ferritin levels have normalized, it is usually advisable to continue therapy for three to six months to allow restoration of tissue iron stores.

A ferric carboxymaltose injection is approved by the U.S. Food and Drug Administration for the treatment of iron-deficiency anemia in patients who have intolerance to oral iron or have had an unsatisfactory response to oral iron [103]. This parenteral iron replacement product is given as a single dose of up to 750 mg of iron via an IV push injection or over a 15-minute infusion followed by a second dose seven days later for a total treatment of up to 1,500 mg of iron [73,103].

Improvements in patient functioning, including less fatigue, resolution of pica, and increased participation in activities of daily living, should be seen within the first week. The Hgb level will rise more slowly, with full resolution expected within six to eight weeks [104].

In DIC, consumption of platelets and clotting factors is preceded by deposition of fibrin in the microcirculation. The patient with XCIC may have bleeding tendencies, tissue damage form ischemia, erythrocyte damage, and hemolysis with a potential for shock. These problems have either occult or overt signs and symptoms. Signs and symptoms of bleeding include epistaxis; petechiae; ecchymosis; bleeding from surgical sites, placental detachment areas, or old sites of injury; positive findings of blood in the stool or emesis; falling blood pressure; postural hypotension; tachycardia; decreased packed red cell volume; and restlessness [106].

Manifestations of thrombosis depend on the specific organ or body system affected. The kidneys are a prime target organ, and hematuria is the most common clinical evidence that the renal system is affected. Thrombosis also can affect the central nervous system; changes in the level of consciousness may signal interruption in cerebral blood flow. Characteristic skin changes such as acrocyanosis, in which the patient experiences generalized sweating with cold, mottled toes and fingers, also occur [106].

A battery of laboratory analyses is used in the diagnosis of DIC in conjunction with the patient's signs and symptoms. These tests measure the patient's coagulation. Platelet counts are decreased; PT and PTT are prolonged. Fibrinogen levels are decreased, and levels of fibrin degradation products (fibrin split products) are elevated. A protamine sulfate test is strongly positive, and the coagulation factor assay demonstrates a reduction in factors II, V, and VII [106].

The pharmacologic management of DIC is controversial. Currently, heparin or blood components such as packed RBCs, platelets, plasma, and factor replacements, or both are used. Some think that DIC is best managed by no treatment at all, because treating the patient's signs and symptoms may worsen the clotting–bleeding phenomenon. The overall goal of therapy is removing the stimulus that initiated the DIC process [106].

The nursing management of patients with DIC is complex. The overall nursing goal is to protect them from bleeding by applying pressure to bleeding sites, avoiding intramuscular injections, keeping the patient's nails trimmed, and having both male and female patients shave with an electric razor instead of a straight-edged razor. The nurse's ability to administer blood products is of primary importance [3].

The patient undergoing heparin sodium or blood component therapy requires additional support and explanations. Heparin may be given either continuously or intermittently by IV drip, and the nurse must closely monitor the prescribed flow rate. The patient receiving heparin must be assessed continuously for bleeding. Blood component therapy, although prescribed to replace depleted coagulation factors consumed by the systemic clotting phenomenon, may stimulate additional clotting. Cryoprecipitate and platelets will also be used. Changes in the patient's level of consciousness, pallor or cyanosis of body parts, or oliguria or anuria, may indicate additional clotting. Notify the physician immediately if these changes occur so the medical management of the patient can be adjusted [3].

Patients with DIC have multiple disease processes simultaneously. They may have malignancy, cardiovascular disease, sepsis, or be pregnant. Therefore, the stress levels of the patient with DIC are high. The patient and family or friends require thorough teaching and psychosocial support to cope effectively with this complex, confusing disease [3].

Clinical manifestations of ITP result from thrombocytopenia. The patient is prone to hemorrhagic episodes. Bleeding tendencies may be minor, involving small petechial hemorrhages of the skin and mucous membranes, but the platelet count may fall low enough to allow central nervous system hemorrhage. The patient may also experience hematuria, hematemesis, melena, gingival oozing, and epistaxis. The female patient who is still menstruating may experience menorrhagia [8].

Diagnostic tests indicate low platelet numbers and alterations in bleeding times. The physician may order a CBC, including quantitative platelet determinations, as well as bone marrow examination to determine the nature of platelet production (megakaryocytopoiesis). Other diagnostic procedures may include determination of bleeding time, Rumple-Leede capillary fragility test (the tourniquet test), and studies of coagulation time and clot retraction [8].

Most patients with acute ITP recover spontaneously and never have a recurrence. Patients with chronic ITP rarely undergo spontaneous remission. After a diagnosis of chronic ITP, steroid therapy is initiated in an attempt to decease or diminish the immunologic (antigen-antibody) response of the reticuloendothelial system and decrease sequestration of thrombocytes by the spleen. The patient continues steroid therapy for several weeks to several months. If the circulating platelet count does not improve, splenectomy may be performed; this procedure usually restores platelet count to normal or near-normal levels by removing the primary organ involved in platelet destruction and the removal of platelets from the circulation [8].

If the patient is anemic from severe blood loss, a diet high in protein and iron should be implemented. Small, frequent meals may be more manageable for the anemic patient [13].

Hospitalization is required for diagnosis of ITP. Nursing care is aimed at both preventing bleeding episodes and promoting patient education about the disease process and the diagnostic procedures. The most common and life-threatening problem is hemorrhage. During hospitalization, monitor the patient continuously for signs or symptoms of hemorrhagic shock. The central nervous system is particularly vulnerable during thrombocytopenia. Therefore, make every effort to provide a safe environment for the thrombocytopenic patient. Suggested nursing interventions during hospitalization include testing urine, stools, and emesis for occult blood; providing footwear for the ambulating patient; avoiding rectal temperature determination, intramuscular injections, and rectal medications; administering platelet concentrates, if needed; and offering mouth rinses composed of hydrogen peroxide and water or normal saline in lieu of routine oral hygiene using toothbrushes [2].

Nursing assessments during hospitalization are related to thrombocytopenia. The progression or resolution of petechial and purpuric hemorrhages needs close monitoring; daily documentation of these lesions by a consistent caregiver is ideal. Pallor or paresthesia of an extremity distal to ecchymotic areas or to hematomas may signal loss of vascular integrity and compromised tissue oxygenation to that extremity. Assess the patient's level of consciousness regularly and immediately report subtle changes in orientation or personality to the physician [2].

The majority of patients with acute ITP have spontaneous remission and may be discharged when platelet counts are greater than 50,000/mcL. Circulating platelets are then regularly assessed (in an outpatient clinic or health provider's office) until the platelet count is normal. Stress that protected headgear may be needed while the patient plays or rides in a car. Teach the signs and symptoms of relapse (increased tendency to bruise, recurrence of petechiae, and epistaxis) [2].

Chronic ITP requires even more challenging nursing management. In addition to the nursing assessments and interventions already mentioned, patient education about steroid therapy is needed. Explain the rationale for its use and the side effects common to steroid consumption. Tell the patient that compliance with the prescribed dose and frequency is of utmost importance in avoiding dangerous or life-threatening complications. Have the patient seek medical attention immediately if for any reason he or she cannot continue taking the medication orally [2].

When conventional conservative steroid therapy is contraindicated, splenectomy is recommended. Additionally, steroid therapy (if the patient is not already weaned) is continued throughout the postoperative period to promote adaptation to the stress of surgery. Platelet concentrations are administered throughout the intraoperative and post-operative periods to decrease the likelihood of more hemorrhagic episodes. After discharge, the patient's platelet level is monitored closely to detect the return to normal levels. Thrombocytopenia usually does not recur following splenectomy, but discharge teaching following surgery should include signs and symptoms indicating a relapse [2].

A major problem for the patient with granulocytopenia is the accurate recognition and diagnosis of infection because its signs and symptoms in the presence of granulocytopenia ae unpredictable. Patients with acute granulocytopenia have the most life-threatening infections. Total WBC counts may dip to less than 500/mcL, the percentage of neutrophils drop, and overwhelming bacterial and fungal sepsis can develop [21].

Fever is present during infection, but the usual signs and symptoms are not typical. Inflammatory response with the production of purulent matter may not present, and the usual natural elevation of leukocytes is not found. Thus, granulocytopenia patients present a difficult diagnostic picture [21].

Suspected infection is treated aggressively with broad spectrum antibiotic therapy. Antimicrobial treatment is initiated as soon as cultures have been taken. After the micro-organism has been identified, the antibiotic regimen can be altered as needed to conform to the sensitivity test. Multiple antibiotics are usually prescribed, and IV delivery is the route of choice [9].

In acute granulocytopenia, bone marrow recovery is usually rapid after the removal of the offending stimulus. The peripheral blood count may show some atypical (immature) forms during the recovery phase, but recovery is usually complete and sustained. In chronic granulocytopenia, androgens and corticosteroids can restore the normal hematologic picture. These agents have not been found useful in the management of acute granulocytopenia, however granulocytes may be administered during the initial stages of acute granulocytopenia [9].

The nurse must identify patients at risk for developing granulocytopenia and have knowledge of medications with potential side effects or adverse reactions of blood dyscrasias. Granulocytopenia is not preventable nor predictable, but anticipation of potential problems may save the patient's life [3].

After infection is suggested, the stimulus precipitating the granulocytopenia is removed, if possible. The most likely cause is a medication, which should be stopped immediately. The patient should be isolated from potential carriers of infection. Visitors may need to be screened. Staff members with bacterial or fungal infections should not come into contact with these patients, and even staff members with minor viral infections should not care for them. Patients with severe granulocytopenia are sometimes placed in protective or reverse isolation. This practice is controversial, however [3].

As already mentioned, the usual signs and symptoms of infection are not reliable with granulocytopenia. Nevertheless, the nurse should monitor the patient's temperature frequently. Continuously assess potential sites of infection, such as the skin and mucous membranes, lungs, ears, mouth, and gastrointestinal and genitourinary tract. Above all, listen to the patient who may provide the best clues to the source of infection [3].

Nursing management of the patient experiencing acute granulocytopenia is similar to that of the patient with leukemia experiencing leukopenia. Patients with chronic granulocytopenia on steroid androgen therapy need emotional support to deal with the body-image side effects of this therapy. Educating them on the potential masculinization effects of both drugs may help them cope when these side effects appear [3].

Additional patient education centers around recognizing signs and symptoms of infection until hematologic recovery occurs and avoiding potential sources of infection. Instruct patients on the method of measuring body temperature using the oral or axillary route, as well as the specific signs and symptoms of infection. In addition, instruct them to seek medical attention immediately with any manifestations of infection. Typically, infections in these patients are from their own normal flora; however, they should still be encouraged to avoid large crowds and contagious people whenever possible [3].

The patient with acquired agammaglobulinemia has current pyogenic infections, especially sinusitis and pneumonia. A sprue-like syndrome is also frequent. The majority of adults with agammaglobulinemia have diarrhea, steatorrhea (fatty stools), protein-losing enteropathy, and malabsorption problems. Another clinical feature is noncaseating granulomas of the liver, spleen, skin, and lungs. Hepatosplenomegaly may be present. Furthermore, these patients have a markedly increased incidence of autoimmune disease, and their immunoglobulin G (IgG) levels are low [19].

Steroid therapy is useful in treating agammaglobulinemia. Lifelong immunoglobulin replacement therapy is necessary to supply missing antibodies; metronidazole, an effective amebicide, is prescribed for patients with the sprue-like syndrome. Patients with this syndrome take a diet free of milk, milk products, and gluten [19].

The nursing management of acquired agammaglobulinemia centers around patient teaching. Topics should include signs and symptoms of infection that necessitate health care; diet and medication instruction for patients having a sprue-like syndrome; and detailed instructions of steroid therapy [3].

Leukemia occurs in acute forms (involving proliferation of immature cells) and chronic forms (involving proliferation of mature cells) and can affect the erythrocyte or any of the white cell precursors. The four most common types of leukemia are: acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and chronic granulocytic leukemia (CGL). The principles guiding nursing management are similar for all the leukemias [108,109].

Acute Lymphocytic Leukemia (ALL)

ALL represents a heterogeneous group of biologic subtypes of leukemia and is classified into two principal types depending on the lymphocytes from which it develops. Most cases of B-lymphocyte ALL originate in cells early in the development of B cells and are therefore designated as precursor B-cell type [110]. Research has demonstrated that childhood ALL is initiated in utero, with another event required for full malignant transformation [111,112]. DNA injury leads to the uncontrolled development of leukemic lymphoblasts in the marrow, which causes a deficiency of normally functioning blood cells. As a result, anemia, thrombocytopenia, and neutropenia occur.

ALL accounts for 82% of leukemias in children and adolescents [113]. The incidence of ALL varies according to sex, age, and race/ethnicity. ALL is more common among male children/adolescents (40 per million) than among female children/adolescents (31 per million) [113]. ALL typically develops in children between 1 and 9 years old, with a sharp peak in the incidence for children 1 to 3 years old [113]. The incidence of ALL is highest in the American Indian/Alaska Native population and lowest in the Black population [113].

Chronic Lymphocytic Leukemia (CLL)

Chronic lymphocytic leukemia is a proliferative disorder of lymphoid tissues. Abnormal and incompetent lymphocytes initially are found in the lymph nodes; the disease progresses to involve the reticuloendothelial system (liver and spleen) and invade the bone marrow. The abnormal and incompetent lymphocytes accumulate in the blood. Eventually, the lining of the respiratory and gastrointestinal tracts, as well as the skin, are infiltrated by leukemic cells. As the disease process continues, abnormal lymphocytes eventually replace normal bone marrow elements. This process interferes with normal myelopoiesis, erythropoiesis, and megakaryocytopoiesis [109].

Unlike ALL, the lymphocytes in CLL are immunologically incompetent. Hypogammaglobinemia is a characteristic of the late stage of the disease. The defect seems to involve immunoglobulin-producing B-lymphocytes. Chronic lymphocytic leukemia has an insidious onset and is usually found by accident upon routine blood count examination. It is the most common leukemia of the Western hemisphere and primarily affects the elderly population [109].

Acute Myeloid Leukemia (AML)

Acute myeloid leukemia refers to a spectrum of hematopoietic malignant diseases, but AML accounts for the majority of cases. Although AML is less prevalent than ALL, AML is more lethal, accounting for approximately 30% of childhood leukemia-related deaths [114]. AML involves the malignant transformation of stem cells or progenitor cells in the bone marrow.

Chronic Granulocytic Leukemia (CGL)

Chronic granulocytic leukemia (CGL) is a malignant disorder characterized by an abnormal and excessive accumulation and overgrowth of mature granulocytes in the bone marrow, blood, and spleen. These abnormalities are associated with a unique chromosomal abnormality, the Ph1 (Philadelphia) chromosome. The granulocytes also seem to have lengthened life spans and may or may not retain their ability to fight infection through phagocytosis [108,109].

The onset and progression of CGL are insidious. Remission may last for as long as four years, but almost 70% of patients undergo an acute transformation, or "blast crisis." In this stage, the leukemia resembles AGL but is not amenable to chemotherapy; death usually occurs within months [108,109].

Approximately 20% of all leukemias in the Western hemisphere are CGL. The disease occurs in adolescence, but it is more likely to occur between 25 and 60 years of age, with the peak incidence in the fourth decade of life. In the neonate, CGL tends to have a rapid progression of infiltration and invasions [108,109].

There is a wide variation in the signs and symptoms of leukemia, and the onset is usually acute. However, in some cases, symptoms are insidious and persistent [110]. On average, symptoms are present for four to six weeks before diagnosis and are associated primarily with leukemia-related pancytopenia [110,115].

In taking a history from the patient and/or a parent or caregiver, the clinician should determine if any of the following symptoms have been present:

A low-grade fever of unknown etiology is the most common symptom associated with ALL [110]. If fever has persisted for more than two weeks, further evaluation for leukemia is warranted. Findings on physical examination that should prompt diagnostic testing for leukemia include pallor, petechiae, ecchymoses of the skin or mucous membranes, or lymphadenopathy (enlargement of more than 2 centimeters). Splenomegaly or hepatomegaly is evident at the time of diagnosis in most patients with acute leukemia [110].

Many of the symptoms related to leukemia are associated with other diseases and conditions, and care is needed in making a differential diagnosis. Lymphadenopathy may be related to infectious mononucleosis or other infection, but a lack of a response to a routine course of antibiotics should prompt laboratory testing consisting of a complete blood cell count (CBC) with differential and a reticulocyte count. The likelihood of leukemia is high when such testing demonstrates anemia, thrombocytopenia, leukopenia, high mean corpuscular volume, and reticulocytopenia [116]. Light microscopy of stained blood cells can demonstrate leukemic blast cells; blast cells may also be present on the peripheral blood smear. However, blast cells are often present in the bone marrow only.

The treatment of leukemia varies according to the type and is risk-adapted. This approach prevents overtreatment of patients at low risk for relapse and provides sufficient cytotoxicity for those at high risk for relapse or treatment failure. Investigators continue to explore both different doses of chemotherapy agents, timing and intensity, and different drug combinations to achieve better rates of remission, disease-free survival, and overall survival.

ALL

With one exception, all types of ALL are treated with an approach that includes the following phases [117]:

The exception to this approach is B-cell ALL. B-cell ALL is histologically similar to Burkitt lymphoma, and it is, therefore, treated according to protocols for advanced Burkitt lymphoma without marrow involvement, which consists of short-term intensive chemotherapy (high-dose methotrexate, cytarabine, and cyclophosphamide) [118,119].

The biologic and molecular characteristics of leukemia are becoming better understood with the advent of genetic technology. As this enhanced knowledge leads to further distinction of subgroups according to molecular characteristics, research is focusing on the development of novel therapies to target molecular abnormalities, a type of treatment that has dramatically changed treatment and outcomes for several types of cancers in adults. Several such drugs are in early studies of children/adolescents with leukemia [120]. Imatinib (an oral drug that has been successful in adults) received FDA approval in 2013 for treatment of pediatric Philadelphia chromosome-positive (Ph+) ALL [121].

AML

The treatment of patients with acute myeloid leukemia (AML) is based on whether the disease is newly diagnosed (previously untreated), in remission, or recurrent. Also, the intensity of the treatment and the patient's overall health status are considered when choosing a treatment approach. Successful treatment of AML requires the control of bone marrow and systemic disease, and specific treatment of central nervous system (CNS) disease, if present. The cornerstone of this strategy includes systemically administered combination chemotherapy. Because only 5% or fewer of patients with AML develop CNS disease, prophylactic treatment is not indicated [122].

CLL

Treatment of patients with chronic lymphocytic leukemia (CLL) must be individualized based on the clinical behavior of the disease. Because this disease is generally not curable, occurs in an older population, and often progresses slowly, it is most often treated in a conservative fashion. Therapy often begins when patients develop profound cytopenias, or when symptoms, such as enlarging bulky lymphadenopathy or debilitating symptoms, substantially impact their quality of life [123].

CML

Treatment of patients with chronic myeloid leukemia (CML) is usually initiated at diagnosis, which is based on the presence of an elevated white blood cell count, splenomegaly, thrombocytosis, and identification of the BCR::ABL1 translocation. The optimal front-line treatment for patients with chronic-phase CML involves specific inhibitors of the BCR::ABL1 tyrosine kinase. Although imatinib mesylate has been extensively studied in patients with CML, TKIs with greater potency and selectivity for BCR::ABL1 than imatinib have also been evaluated. Bariatric surgery may impede proper absorption of oral TKIs, resulting in suboptimal responses. Allogeneic BMT or SCT has also been used with curative intent [124].

Nursing care of all patients with leukemia centers around preventing complications of bleeding and infection. Provide information on potential or actual neutropenia, anemia, and thrombocytopenia caused by replacement of the normal bone marrow cellular element by leukemic cells or destruction by antineoplastic chemotherapy. Chemotherapeutic treatment also can lead to bone marrow suppression [3].

Hodgkin lymphoma was first described in 1832 by Thomas Hodgkin as a "peculiar enlargement" and "affection" of the lymph nodes of the neck and other areas of the body, along with enlargement of the spleen and possibly the liver; there were often deposits of firm tubercle-like nodules in the spleen and liver [125]. The malignant cells, subsequently named Reed-Sternberg cells, arise from B lymphocytes and exist with Hodgkin cells (large, mononuclear cell variants) within an immunoreactive background consisting of lymphocytes, eosinophils, neutrophils, histiocytes, plasma cells, fibroblasts, and collagen [125]. According to the WHO/REAL system, Hodgkin lymphoma may be categorized as classical and nonclassical [126]. Classical Hodgkin lymphoma is further categorized into four subtypes: lymphocyte predominant, nodular sclerosis, mixed cellularity, and lymphocyte depleted [126,127,128].

Clinical Manifestations

The clinical presentation of lymphoma is similar to that of leukemia in several ways, and the course of diagnostic testing is also similar. However, some signs and symptoms of lymphoma are distinct from those of leukemia. Furthermore, there are differences even between the two types of lymphoma, especially with regard to the sites of disease.

Imaging studies are done not only to determine or confirm the presence of lymphoma but also to assess the extent of disease, which assists in staging as well as in establishing a baseline for monitoring response to treatment. As with leukemia, immunophenotyping and cytogenetic analysis are done to determine the cell lineage of disease, evaluate the pattern of CD antigen expression, and identify chromosomal abnormalities. The role of these studies in the diagnosis of lymphoma is not discussed here, as other factors currently play a more significant role in prognosis.

The suspicion of Hodgkin lymphoma is increased when B symptoms are present with lymphadenopathy or splenomegaly. Patients may also have nonspecific systemic symptoms, such as fatigue and anorexia. In some patients, generalized pruritus may be present for months before lymphadenopathy is found, and excoriations may be evident as a result of excessive scratching [129]. On physical examination, the most common finding is a persistent, painless adenopathy, usually in the supraclavicular or cervical area [116,129]. As noted, reactive lymphadenopathy is common in children/adolescents, making it necessary to carefully evaluate patients to first rule out other infectious or inflammatory conditions. Involvement of the supraclavicular nodes should prompt earlier evaluation for Hodgkin lymphoma, as the cervical nodes are most commonly involved in infection and inflammatory conditions. Infectious mononucleosis can be distinguished from Hodgkin lymphoma by the presence of symmetrical cervical lymphadenopathy with pharyngitis. A tuberculin test may be helpful to rule out tuberculosis, which also may have similar clinical characteristics.

Classification and Staging

Hodgkin lymphoma is classified histologically according to four subtypes. Nodular sclerosis is the most common subtype, representing approximately 72% of the cases of pediatric Hodgkin lymphoma. This subtype occurs most frequently in adolescents, and the mediastinum is involved in 80% of cases [125]. Mixed cellularity Hodgkin lymphoma accounts for approximately 25% of pediatric Hodgkin lymphoma, most frequently developing in children younger than 10 years of age [125]. It is usually associated with the peripheral lymph nodes of the upper part of the body.

The American Joint Committee on Cancer has adopted the Lugano classification system to evaluate and stage lymphoma. The Lugano system replaces the Ann Arbor classification system (which was adopted in 1971). The Lugano system categorizes the disease as stage I through IV according to the extent of lymph node involvement [130]. The system is based on the premise that Hodgkin lymphoma progresses along contiguous lymph nodes [131]. Within this classification system there are additional designations that are applied to further define symptoms and disease [131].

Diagnostic Tests

The diagnostic work-up for suspected Hodgkin lymphoma includes laboratory testing and imaging studies to evaluate the site and extent of disease. Laboratory testing should begin with a CBC with differential and an erythrocyte sedimentation rate. The results of the CBC may be nonspecific, demonstrating neutrophilia, eosinophilia, and thrombocytosis [125,129]. Lymphopenia and normochromic normocytic anemia are indicators of extensive disease [132,133]. In the presence of other signs of Hodgkin lymphoma, elevations of the erythrocyte sedimentation rate, lactate dehydrogenase level, and ferritin level may be further indicators of Hodgkin lymphoma [116]. An elevated level of alkaline phosphatase may indicate metastatic bone disease, and further testing should be done to determine if there is skeletal involvement [129].

Evaluation of a bone marrow sample is usually not routinely done. Bone marrow involvement is a characteristic of primarily lymphocyte-depleted Hodgkin lymphoma, which is rare in the pediatric population; approximately 10% to 15% of children/adolescents will have bone marrow involvement at the time of the initial diagnosis [125]. The frequency of bone marrow involvement is higher for older male children who have constitutional symptoms. Bone marrow biopsy should be limited to patients who have B symptoms and in whom advanced disease is suspected [129].

A diagnosis of Hodgkin lymphoma can be confirmed only through evaluation of a specimen from an involved lymph node, and biopsy should be done when there is no response to a course of antibiotics. The biopsy technique depends on the site of the involved node. Excisional biopsy is often the preferred technique, as it allows for better determination of the histologic subtype [129]. However, the least invasive procedure should be used [134,135]. Thus, fine-needle aspiration may be more appropriate if the involved node is in the thoracic or abdominal cavity, and CT can be used to guide biopsy in these situations.

Therapeutic Measures

The National Comprehensive Cancer Network recommends that treatment of patients with favorable-risk Hodgkin lymphoma typically involve participation in an ongoing clinical trial.

(https://www.nccn.org/professionals/physician_gls/pdf/ped_hodgkin.pdf Last Accessed: September 29, 2025)

Level of Evidence: Expert Opinion/Consensus Statement

The risk-adaptive approach to the treatment of Hodgkin lymphoma involves planning treatment according to prognostic variables such as stage of disease, presence of B symptoms, and tumor bulk [136]. Disease is classified as being low, intermediate, or high risk. Low-risk disease is defined as localized Hodgkin lymphoma (stage I or II and sometimes IIIA) with no B symptoms or tumor bulk. Intermediate-risk disease usually includes stage I or II disease with unfavorable features (B symptoms, tumor bulk, involvement of three or more lymph node regions, and/or extranodal extension to contiguous structures) [129]. Stages III and IV typically represent high-risk disease.

Ongoing trials for patients with favorable-risk (low-risk) disease are evaluating the effectiveness of treatment with fewer cycles of combination chemotherapy alone that limit doses of anthracyclines, alkylating agents, and radiation therapy. Contemporary trials for patients with intermediate/unfavorable disease are testing whether chemotherapy and radiation therapy can be limited in patients who achieve a rapid early response to dose-intensive chemotherapy regimens. Trials are also testing the efficacy of regimens integrating novel, potentially less-toxic agents such as brentuximab vedotin [137].

Specific Nursing Measures

Nursing management of the patient with Hodgkin disease is complex. Emotional support and patient education are important in all phases of care. Even patients with disseminated disease have a chance for long-term disease-free periods, and those with localized disease have an excellent chance for cure [138].

During the diagnostic phase, the patient may seem overwhelmed by the number and invasiveness of the diagnostic procedures. Explain all procedures thoroughly to the patient and family. Be alert to the need to have questions clarified and to ventilate feelings [138].

The remission-induction phase brings new challenges to the patient, the patient's family or friends, and the nurse. These patients are prone to the same problems as anyone receiving radiation therapy or chemotherapy. Because the majority of patients with Hodgkin disease are between 20 and 40 years of age and are receiving radiation therapy, chemotherapy, or both, reproduction may be impaired. Sperm banking offers the male patient the possibility of fathering a normal offspring at a later time. Especially troublesome are problems caused by nausea and vomiting, bone marrow suppression, and alopecia. The patient with nausea and vomiting is prone to developing disturbances in electrolyte balance. Thus, antiemetics should be given routinely, and IV fluids must be regulated to maintain homeostasis [138]

Bone marrow suppression can lead to leukopenia, anemia, and thrombocytopenia. These conditions make the patient prone to the problems of infection, deficits of oxygen transport, and major and minor bleeding episodes. Monitor the patient's complete blood count and note when the values are low. These patients are at great risk for Pneumocystis carinii pneumonia [138].

During leukopenia episodes, the major nursing goal is prevention of infection. Patients should avoid crowds and frequently assess themselves for signs and symptoms of infection. This self-assessment necessitates detailed instructions by the nurse [138].

Oxygen transport problems may be caused by anemia or a large mediastinal mass. Patients with these problems should be encouraged to alternate activity with rest periods. Use of a Flower's or semi-Fowler's position for resting or sleeping may relieve dyspnea. Monitoring the patient's heart and respiratory rates before and after activity may provide clues to the patient's ability to tolerate activity. When anemia is severe, administer blood component therapy in the form of packed RBCs [138].

Overt or occult bleeding episodes are another patient problem caused by bone marrow suppression. Special oral hygiene using soft toothbrushes may be needed to prevent gingival oozing. Straight-edged razors and drugs interfering with platelet function are contraindicated [138].

Body image changes may be difficult for the patient to endure and may damage self-esteem. Patients 20 to 40 years of age (the age group most commonly affected by Hodgkin disease) undergo many changes. They are establishing intimate relationships, planning families, and attaining career goals. This is one of the most productive periods of life. The diagnosis of Hodgkin disease, even with its good chance for cure, still brings the fears associated with cancer. Fertility may be impaired for the patient receiving radiation therapy or antineoplastic chemotherapy. The therapies are teratogenic; they cause an increased rate of spontaneous abortion or genetically defective offspring. Feeling of loss of control, rejection, and isolation may overwhelm the patient [138].

The nurse is in a prime position to offer these patients emotional support, restore feelings of control, and relief from some of the feelings or rejection and isolation. Establish a trusting relationship as early as possible in the diagnostic phase. Use a calm, unhurried, reassuring approach whenever interacting with these patients. Provide accurate information about Hodgkin disease, radiation therapy, and chemotherapy, and correct misconceptions about the disease process. Allow patients to make decisions about their schedules whenever possible. Attempt to meet any physical and emotional needs they may have [138].

Non-Hodgkin lymphoma is a heterogeneous group of malignant tumors of lymphoreticular cells that arise from both mature and blastic B cells and T cells [139]. Non-Hodgkin lymphomas in children/adolescents differ from those in adults in that adult lymphomas are more clinically aggressive.

There are nearly 30 different types of non-Hodgkin lymphoma. In children the most common are Burkitt lymphoma and diffuse large B cell lymphomas (both developing from B lymphocytes) and anaplastic large-cell lymphoma and lymphoblastic lymphoma (which typically arise from T cells). In adults, the most common type is diffuse large B-cell lymphoma.

Clinical Manifestations

The clinical evaluation and diagnostic testing for non-Hodgkin lymphoma is similar to that for Hodgkin lymphoma. Lymphadenopathy should be evaluated, and infectious or inflammatory conditions should be ruled out before a biopsy is performed. The sites of disease and associated symptoms vary according to the histopathologic type of non-Hodgkin lymphoma [140,141,142]. Most patients will have advanced disease at the time of presentation [141,143].

Therapeutic Measures

As with Hodgkin lymphoma, the treatment of non-Hodgkin lymphoma is based on the extent of disease, with the intensity of treatment being increased for more extensive disease [144]. Because non-Hodgkin lymphoma in children is considered to be widely disseminated from the outset, even when apparently localized, combination chemotherapy is recommended for most patients [143]. The event-free survival has been better in some studies in which surgical resection was done. So, there may be some value to this approach if resection can be readily accomplished, especially in cases of large tumor masses [140]. Treatment often consists of a cytoreduction phase to reduce tumor burden, followed by a consolidation phase.

For most studies of treatments done in the United States, patients are categorized into three risk groups: low-risk, which is completely resected stage I disease or stage II abdominal disease; high-risk, which consists of CNS involvement with or without bone marrow involvement; and intermediate-risk, which encompasses disease that is not eligible for the other two groups [140]. Treatment also varies according to the pathologic subtype.

B-cell non-Hodgkin lymphoma can be treated with two or three cycles of combination chemotherapy after surgical resection if there is no measurable tumor burden [143,144,145]. The combination of vincristine, cyclophosphamide, doxorubicin, and prednisone has been highly effective in this setting [119]. A single-agent phase II study of rituximab performed by the BFM group showed activity in Burkitt lymphoma [146]. A pilot study from the COG added rituximab to baseline chemotherapy with FAB/LMB-96 therapy in patients with stage III and stage IV B-cell non-Hodgkin lymphoma [147,148]. For higher risk disease, the addition of two or three courses of chemotherapy, high-dose methotrexate, and high-dose cytarabine was also effective [119,149,150].

It is not unusual for a diagnosis of MM to be determined during a routine physical examination in patients who have presented to the physician's office with totally unrelated symptoms [151]. Blood work usually initially reveals anemia or renal insufficiency, warranting further investigation. In the majority of patients, MM manifests itself between the fifth and seventh decades of life. Many patients attribute their symptoms of lower back or rib pain, fatigue, weakness, and feeling out of breath on exertion to the normal aging process. Patients report their back pain is not relieved at night when resting and increases with a change in position. Neurologic involvement, with paresthesias and sensory loss in the extremities, may also be a presenting symptom [156,157,158]. Patients may voice some frustration during the prediagnosis period, reporting frequent office visits for upper respiratory or recurrent urinary tract infections that never completely resolve.

For people with newly diagnosed myeloma or smoldering myeloma who have not had whole-body imaging with one of the following, the National Collaborating Centre for Cancer recommends whole-body imaging be considered to assess for myeloma-related bone disease and extra-medullary plasmacytomas with MRI, CT, or fluorodeoxyglucose positron emission tomography CT.

(https://www.nice.org.uk/guidance/ng35 Last Accessed: September 29, 2025)

Level of Evidence: Expert Opinion/Consensus Statement

Upon initial diagnosis, approximately 80% of the patients have pathologic disease with punched out areas of bone due to lytic lesions; some will have evidence of fractures [151,155]. Anemia, which may be quite severe, is the most common cause of weakness in patients with MM [151]. Seventy percent of patients presenting with this disease have anemia, and approximately 20% will have an elevated serum creatinine, showing signs of acute or chronic renal impairment [159]. Obviously, a more advanced stage of disease will reveal increased organ involvement or damage, evidenced by hypercalcemia and lytic bone lesions. For patients presenting with a more aggressive disease, this poses a serious problem requiring prompt intervention to halt the disease process [156,160,161]. Higher-risk patients are candidates for clinical trials at the discretion of the clinician [156]. The hallmarks of the disease—calcium elevation, renal insufficiency, anemia, and bone disease—are known by the acronym CRAB [155,162].

A risk-adapted, personalized approach is the most rational way to treat MM as it helps to ensure that patients are not undertreated (for aggressive disease) or overtreated (for indolent disease that will be slow to relapse), and there are many effective agents and combinations with differing indications and safety profiles [162]. Individuals with aggressive disease, younger biologic age, and few comorbidities typically receive intensive therapy (i.e., continuous high-dose therapy with autologous stem-cell transplant). Patients with nonmalignant smoldering or asymptomatic MM may require no immediate active treatment (e.g., no chemotherapy or immunomodulators) or therapy that is less intense and/or in intervals. Furthermore, treatments are tailored to variations in host and disease characteristics, sparing patients from excessive toxic effects.

For patients with symptomatic disease, treatment should begin as soon as possible. Modalities include [156,162]:

Various combinations of these modalities are often used.

The basic pathologic changes associated with polycythemia vera are caused by hypervolemia and hyperviscosity of the blood from erythrocytosis. Because this disorder is systemic, clinical manifestations are varied and may not suggest the underlying disease process. Any organ system may be involved [60].

Patients have alterations in their peripheral blood counts. The thermogram shows elevated levels of hemoglobin, circulating erythrocytes, hematocrit, and reticulocytes. Leukocytosis and thrombocytosis are also present. As in many myeloproliferative disorders, the basal metabolic rate is elevated without any evidence of alteration in thyroid function. Hyperuricemia and hyperuricosuria are also evident in the presence of leukocytosis. Symptoms of gouty arthritis may become apparent if uric acid levels are left untreated [60].

Patients may have elevated systolic and diastolic blood pressure, left ventricular hypertrophy, palpitations, and angina in response to the increase workload on the heart. Other cardiovascular signs and symptoms include dizziness, exertional dyspnea, and peripheral edema. Sluggish circulation with resultant thrombi formation may precipitate infarctions of the spleen, heart, and brain. CNS symptoms are the most frequent. Disturbances in cerebral blood flow may cause headaches, vertigo, tinnitus, and visual problems such as diplopia and blurred vision. Hypervolemia and consequent venous distention can cause esophageal varices and hemorrhoids. As already mentioned, hemorrhage can ensue when vessels are weakened and damaged. Some hemorrhages, such as bleeding esophageal varices, may be life threatening. Other bleeding may be minute, such as petechiae and ecchymosis. Epistaxis is common [60].

Peptic ulcer disease is 10 times more common in polycythemia vera patients than in the general population. The exact reason for this increased incidence is unknown. The predilection may involve thrombi formation to the stomach and ileum, or a disequilibrium between the gastric mucin and hydrochloric acid secretion may leave the gastric and intestinal mucosa unprotected by mucin [60].

Phlebotomy of pharmacotherapy is often used to return the thermogram rapidly to relative normalcy. After the peripheral blood count is normalized, radiation therapy or chemotherapy is begun [60].

The patient with polycythemia vera who has an increased basal metabolic rate may have lost weight before diagnosis. Small, frequent, high-calorie, high-protein meals should be served. Dietary supplements high in calories and protein may need to be added to the patient's nutritional regimen. The nurse should make mealtimes pleasant and productive and monitor the patient's weight carefully [60].

Regardless of whether there is an elevated basal metabolic rate or peptic ulcer disease, maintaining adequate hydration is essential for these patients. Dehydration compounds the hyperviscosity of polycythemia vera and may precipitant thrombotic episodes [60].

Nursing management of patients with polycythemia vera patients centers around reducing hypervolemia and hyperviscosity. Phlebotomy is not without risk. Volume loss may precipitate signs and symptoms of shock, so the assessment of vital signs and the signs and symptoms of hypovolemia during phlebotomy is crucial. Repeated phlebotomies may be necessary to reduce the viscosity of the blood adequately, and iron-deficiency anemia can result. Supplemental iron can correct this deficiency. Phlebotomy does not correct the panmyelosis of this disease; it only reduces hypervolemia and hyperviscosity. Nurses should keep the patient well hydrated [2].

When chemotherapeutic agents are administered, assess their adverse or toxic effects. Close monitoring of the peripheral blood count is necessary. Hyperuricemia can result from a dramatic and rapid deduction in leukocytes. A decreasing urinary output seen while accurately measuring the patient's intake and output may be the first indication of uric acid nephropathy. Stress the need for adequate activity to promote vascular integrity, prevent stasis, and promote a sense of control over life. Because these patients have a life expectancy of approximately 13 years after diagnosis, it is essential for them to return to their usual patterns of everyday life [2].

Patient education is another important aspect of nursing management to improve compliance with the medical and nutrition regiments. In addition, patient education may foster autonomy and sense of control over the disease process. Instruction should include explanations of the disease process, the rationale for phlebotomy and radiation therapy or chemotherapy, the importance of compliance with the dietary prescription and fluid needs, and the effectiveness of maintaining optimum activity levels. Encourage patients who smoke to reduce their smoking or stop altogether. Over a long time, smoking increases the hematocrit level, increasing the viscosity of the blood [2].

The patient has one brother, 3 years of age, who is in apparent good health. The family history is unremarkable with one exception: The paternal grandmother died at 62 years of age from gastric cancer. The patient has not been exposed to ionizing radiation.

The patient's developmental milestones are on target. She can tie her shoes, print her own name, and likes to help with household tasks. She has no known allergies and is on no prescription or over-the-counter medications.

The physician completes a physical examination and orders CBC with differential and peripheral smear, a metabolic panel, and inflammatory markers. She also requests iron, vitamin B12, and folate levels.

On assessment, the child appears alert and interactive, but tired. Her height and weight are within normal limits. Assessment of vital signs finds:

Multiple ecchymoses and petechiae are noted on the arms, legs, and trunk, inconsistent with the reported level of activity. The patient also displays mild pallor of the skin and conjunctiva. The liver edge is palpable 3 cm below the right costal margin, and the spleen is palpable 2 cm below the left costal margin. Non-tender cervical and axillary lymphadenopathy is present. No bone or joint deformities are observed, though the child reports intermittent leg pain when asked directly.

Results of initial laboratory tests are as follows:

The constellation of unexplained bruising, pallor, hepatosplenomegaly, lymphadenopathy, and leg pain, combined with laboratory evidence of anemia, thrombocytopenia, leukocytosis with circulating blasts, and elevated LDH, is highly suggestive of ALL. Further diagnostic confirmation with bone marrow aspiration and immunophenotyping would be the next step.

In this patient, trauma-related tissue injury and the ongoing systemic inflammatory response were identified as the triggers for DIC. Supportive care included close hemodynamic monitoring, oxygen therapy, and judicious fluid and blood product replacement. Transfusion therapy was initiated with platelets, fresh frozen plasma, and cryoprecipitate to correct consumptive losses and restore hemostatic balance. Replacement was guided by serial laboratory values, aiming to maintain platelet counts above 50 ×10⁹/L in the presence of active bleeding, fibrinogen above 150 mg/dL, and near-normalization of PT and aPTT.

Although low-dose heparin can be considered in patients with DIC who have prominent thrombotic complications (e.g., purpura fulminans or extensive venous thrombosis), it is contraindicated in actively bleeding patients such as this one. Instead, therapy focused on supportive replacement and careful monitoring for organ dysfunction.

The patient's presentation is consistent with iron-deficiency anemia, the most common cause of anemia worldwide. In men, particularly those older than 50 years of age, iron-deficiency anemia should be considered a diagnosis of exclusion until a bleeding source is identified, most often within the GI tract. Chronic NSAID use may increase the risk of occult GI blood loss through mucosal injury and ulceration.