94850 • Sickle Cell Disease

Table of Contents

94850 • Sickle Cell Disease

How to Receive Credit

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Individual State Nursing Approvals

Special Approvals

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planners

Division Planners Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. PATHOPHYSIOLOGY

3. TREATMENT

4. CASE STUDY

Works Cited

94850 • Sickle Cell Disease

Mark Rose, BS, MA, LP

www.netce.com

Copyright © 2025 NetCE, All rights reserved.

In the United States, an estimated 100,000 people are afflicted by sickle cell disease, and 2,000 infants are born with sickle cell disease annually. This course will review the epidemiology of sickle cell disease; the genetic subtypes (HbSS, HbSC, and HbS beta-thalassemia); and the pathophysiology driving hemoglobin polymerization, vaso-occlusion, and pain. The course emphasizes recognition of the four phases of acute pain crises and timely intervention, alongside practical strategies for prevention counseling, first-line disease modification with hydroxyurea, and acute and chronic pain management using parenteral opioids, NSAIDs, and safe transitions to oral regimens.

94850 • Sickle Cell Disease

Education Category. Infection Control / Internal Medicine

Release Date. 11/01/2025

Expiration Date. 10/31/2028

How to Receive Credit

To complete this course for continuing education credit please go to http://www.netce.com/course/3253 in your browser.

For assistance with receiving continuing education credit, please contact us at help@netce.com.

Course Overview

In the United States, an estimated 100,000 people are afflicted by sickle cell disease, and 2,000 infants are born with sickle cell disease annually. This course will review the epidemiology of sickle cell disease; the genetic subtypes (HbSS, HbSC, and HbS beta-thalassemia); and the pathophysiology driving hemoglobin polymerization, vaso-occlusion, and pain. The course emphasizes recognition of the four phases of acute pain crises and timely intervention, alongside practical strategies for prevention counseling, first-line disease modification with hydroxyurea, and acute and chronic pain management using parenteral opioids, NSAIDs, and safe transitions to oral regimens.

Audience

This course is designed for physicians, PAs, and nurses involved in the care of patients with sickle cell disease.

Accreditations & Approvals

In support of improving patient care, TRC Healthcare/NetCE is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. NetCE is accredited by the International Accreditors for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.

Designations of Credit

This activity was planned by and for the healthcare team, and learners will receive 1 Interprofessional Continuing Education (IPCE) credit(s) for learning and change. NetCE designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. NetCE designates this continuing education activity for 1 ANCC contact hour(s). NetCE designates this continuing education activity for 0.5 pharmacotherapeutic/pharmacology contact hour(s). NetCE designates this continuing education activity for 1.2 hours for Alabama nurses. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME. Successful completion of this CME activity, which includes participation in the evaluation component, enables the learner to earn credit toward the CME and/or Self-Assessment requirements of the American Board of Surgery's Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit. This activity has been approved for the American Board of Anesthesiology’s® (ABA) requirements for Part II: Lifelong Learning and Self-Assessment of the American Board of Anesthesiology’s (ABA) redesigned Maintenance of Certification in Anesthesiology Program® (MOCA®), known as MOCA 2.0®. Please consult the ABA website, www.theABA.org, for a list of all MOCA 2.0 requirements. Maintenance of Certification in Anesthesiology Program® and MOCA® are registered certification marks of the American Board of Anesthesiology®. MOCA 2.0® is a trademark of the American Board of Anesthesiology®. Successful completion of this CME activity, which includes participation in the activity with individual assessments of the participant and feedback to the participant, enables the participant to earn 1 MOC points in the American Board of Pediatrics' (ABP) Maintenance of Certification (MOC) program. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABP MOC credit. This activity has been designated for 1 Lifelong Learning (Part II) credits for the American Board of Pathology Continuing Certification Program. Through an agreement between the Accreditation Council for Continuing Medical Education and the Royal College of Physicians and Surgeons of Canada, medical practitioners participating in the Royal College MOC Program may record completion of accredited activities registered under the ACCME's "CME in Support of MOC" program in Section 3 of the Royal College's MOC Program. AACN Synergy CERP Category A. NetCE is authorized by IACET to offer 0.1 CEU(s) for this program.

Individual State Nursing Approvals

In addition to states that accept ANCC, NetCE is approved as a provider of continuing education in nursing by: Alabama, Provider #ABNP0353 (valid through July 30, 2029); Arkansas, Provider #50-2405; California, BRN Provider #CEP9784; California, LVN Provider #V10662; California, PT Provider #V10842; District of Columbia, Provider #50-2405; Florida, Provider #50-2405; Georgia, Provider #50-2405; Kentucky, Provider #7-0054 through 12/31/2025; South Carolina, Provider #50-2405; West Virginia RN and APRN, Provider #50-2405.

Special Approvals

This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency.

Course Objective

The purpose of this course is to provide clinicians with the information necessary to identify and appropriately manage sickle cell disease in accordance with evidence-based guidelines.

Learning Objectives

Upon completion of this course, you should be able to:

1. Recall the epidemiology and pathophysiology of sickle cell disease.

2. Evaluate options available for the management of pain associated with sickle cell disease.

Faculty

Mark Rose, BS, MA, LP, is a licensed psychologist in the State of Minnesota with a private consulting practice and a medical research analyst with a biomedical communications firm. Earlier healthcare technology assessment work led to medical device and pharmaceutical sector experience in new product development involving cancer ablative devices and pain therapeutics. Along with substantial experience in addiction research, Mr. Rose has contributed to the authorship of numerous papers on CNS, oncology, and other medical disorders. He is the lead author of papers published in peer-reviewed addiction, psychiatry, and pain medicine journals and has written books on prescription opioids and alcoholism published by the Hazelden Foundation. He also serves as an Expert Advisor and Expert Witness to law firms that represent disability claimants or criminal defendants on cases related to chronic pain, psychiatric/substance use disorders, and acute pharmacologic/toxicologic effects. Mr. Rose is on the Board of Directors of the Minneapolis-based International Institute of Anti-Aging Medicine and is a member of several professional organizations.

Faculty Disclosure

Contributing faculty, Mark Rose, BS, MA, LP, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planners

John V. Jurica, MD, MPH

Margo A. Halm, RN, PhD, NEA-BC, FAAN

Division Planners Disclosure

The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. INTRODUCTION

In the United States, an estimated 100,000 people are afflicted by sickle cell disease and 2,000 infants are born with sickle cell disease annually [1,2]. Sickle cell disease is predominantly found in persons of African descent; other groups with heightened risk include those of South or Central American, Caribbean, Mediterranean, Indian, and Saudi Arabian descent (typically areas in which malaria is endemic) [2,3]. The condition is chronic and lifelong and is associated with a decreased lifespan. Median survival in the United States is 42 years for men and 48 years for women, although innovations in disease management are improving long-term survival [4].

There are three main types of sickle cell disease defined by the specific genetic combination [2]. The most severe form is HbSS, commonly referred to as sickle cell anemia. 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 beta^0) and "plus" (HbS beta+). Those with HbS beta^0-thalassemia usually have a severe form of sickle cell disease, while those with HbS beta+ tend to have a milder form [2].

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 [5]. 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 [1]:

- Prodromal: Lethargy and mild localized pain may develop, but hematologic changes have not yet occurred.

- Initial infarctive: Pain intensity increases from mild to moderate, hemoglobin decreases, and alterations in mood develop. Laboratory findings lag behind patient self-report of symptoms. Prompt physician attention to patient report of symptom onset is essential to initial management.

- Post-infarctive/inflammatory: Severe pain peaks, with intensity that causes patients to seek emergency department or hospital care for pain relief. Laboratory changes include increases in reticulocyte count, lactate dehydrogenase, and C-reactive protein. During crisis, C-reactive protein levels can rise to 70 mg/L, compared with an average 32.2 mg/L in patients with sickle cell disease not in crisis and 10 mg/L in persons without sickle cell disease.

- Resolution: Pain during crisis returns to a moderate intensity following adequate fluid hydration and intravenous analgesics.

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 [6].

2. PATHOPHYSIOLOGY

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 [7]. 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 [8]. 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 [8].

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 [1]. Neuropathic pain is uncommon [2]. 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 [2].

The most common chronic pain syndromes in sickle cell disease include [2]:

- Arthritis

- Arthropathy

- Aseptic (avascular) necrosis

- Leg ulcers

- Vertebral body collapse

3. TREATMENT

No single treatment is effective for all people with sickle cell disease; instead, appropriate treatment options are determined according to symptom severity [2]. Nonpharmacologic prevention includes avoiding dehydration, extreme temperatures, high altitudes (including flying), and low oxygen levels from intense exercise or athletic training [2,9].

For prevention of acute pain episodes, hydroxyurea is most often used [3]. 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 [3,10]. 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.

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 [2]. 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 [2].

L-glutamine (Endari) is approved for patients 5 years of age and older to reduce acute complications of sickle cell disease [10,11]. 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 [10,11].

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 [10,11].

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) [10,12,13]. 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 [12,13].

Adjunctive medications may also be indicated. Parenteral NSAIDs can reduce opioid requirements and provide greater ease in transition to oral analgesics [1]. 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 [1].

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 [1]. 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 [2].

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 [2,9].

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 [14].

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 [9].

4. CASE STUDY

Patient A, a Black woman 26 years of age, presents with two days of escalating bone pain centered in the lower back and shins, radiating to the hips. She reports recent stress as the result of the breakup of a long-term relationship.

The patient notes that she noticed marked lethargy and mild localized pain at home a few days ago. The pain intensified from mild to moderate, and she noted mood changes. Today, the pain intensified to severe, leading her to seek emergency care. Her laboratory tests show elevated reticulocyte count and lactate dehydrogenase, with a marked rise in C-reactive protein.

After assessment and laboratory testing, Patient A is diagnosed with HbSS sickle cell disease, defined by inheritance of a sickle cell gene from each parent. The underlying single nucleotide mutation causes hemoglobin to polymerize when deoxygenated, producing sickled red cells that increase blood viscosity and occlude the microvasculature. The resultant ischemia explains the acute and chronic pain patterns and multi-organ risks.

In the emergency department, Patient A is started on intravenous fluids. To address her severe pain, parenteral morphine and corticosteroids are initiated. After she stabilizes, a parenteral NSAID is added to reduce opioid requirements and facilitate transition to oral therapy. Transfusion is not required for this episode, as she did not have severe anemia. If severe anemia were present—particularly with infection or splenomegaly—blood transfusion would be considered.

Hydroxyurea at a daily dose 15 mg/kg of is initiated as the backbone of disease modification to reduce pain crises, transfusion needs, and mortality. The patient is counseled on the importance of adherence, noting clinical response often begins after three to six months; more frequent follow-up and encouragement are planned to support adherence. L-glutamine is discussed as an option to reduce acute complications and hospitalizations, but use is deferred.

Prevention counseling focuses on avoidance of dehydration, extreme temperatures, high altitudes (including flying), and low-oxygen states from intense exercise or athletic training.

Hematopoietic stem cell transplantation is the only known cure for sickle cell disease. It requires close donor-recipient HLA matching and is suitable for a limited subset of patients. Patient A is informed about indications and risks, with agreement to revisit this option if a suitable donor is identified.

Close follow-up was arranged to titrate hydroxyurea as necessary and monitor clinical response. Pain management follow-up is also scheduled to optimize long-acting and rescue medications and incorporate adjuvants, as needed.

At two-week follow-up, Patient A reports improved baseline pain and no new crises. She is adhering to hydration and temperature-avoidance guidance, remains adherent to hydroxyurea therapy, and feels supported by the outlined plan. Ongoing monitoring is planned to evaluate response over the next three to six months, with consideration of adding crizanlizumab or L-glutamine if breakthrough crises persisted despite optimized hydroxyurea therapy.

Works Cited

1. Gregory TB. Chronic pain perspectives: Sickle cell disease: gaining control over the pain. J Fam Pract. 2012;61(9 Suppl):S5-S8.

2. Centers for Disease Control and Prevention. Sickle Cell Disease. Available at https://www.cdc.gov/sickle-cell/about/index.html/. Last accessed October 25, 2025.

3. Brawley OW, Cornelius LJ, Edwards LR, et al. National Institutes of Health Consensus Development Conference Statement: hydroxyurea treatment for sickle cell disease. Ann Intern Med. 2008;148(12):932-938.

4. World Health Organization. Sickle-Cell Anaemia. Available at http://apps.who.int/gb/archive/pdf_files/WHA59/A59_9-en.pdf. Last accessed October 25, 2025.

5. Centers for Disease Control and Prevention. Sickle Cell Disease. What is Sickle Cell Trait? Available at https://www.cdc.gov/sickle-cell/sickle-cell-trait/index.html. Last accessed October 25, 2025.

6. McClish DK, Smith WR, Dahman BA, et al. Pain site frequency and location in sickle cell disease: the PiSCES project. Pain. 2009;145(1-2):246-251.

7. Hsieh MM, Fitzhugh CD, Tisdale JF. Allogeneic hematopoietic stem cell transplantation for sickle cell disease: the time is now. Blood. 2011;118(5):1197-1207.

8. Taylor LE, Stotts NA, Humphreys J, Treadwell MJ, Miaskowski C. A review of the literature on the multiple dimensions of chronic pain in adults with sickle cell disease. J Pain Symptom Manage. 2010;40(3):416-435.

9. National Heart, Lung, and Blood Institute. What Is Sickle Cell Disease? Available at https://www.nhlbi.nih.gov/health/sickle-cell-disease. Last accessed October 25, 2025.

10. LexiDrug. Available at https://online.lexi.com. Last accessed October 25, 2025.

11. National Heart, Lung, and Blood Institute. Sickle Cell Disease: Treatment. Available at https://www.nhlbi.nih.gov/health/sickle-cell-disease/treatment. Last accessed October 25, 2025.

12. U.S. Food and Drug Administration. FDA is Alerting Patients and Health Care Professionals About the Voluntary Withdrawal of Oxbryta From the Market Due to Safety Concerns. Available at https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerting-patients-and-health-care-professionals-about-voluntary-withdrawal-oxbryta-market-due#. Last accessed October 25, 2025.

13. Pfizer. Press Release. Pfizer Voluntary Withdraws All Lots of Sickle Cell Disease Treatment OXBRYTA (voxelotor) From Worldwide Markets. Available at https://www.pfizer.com/news/press-release/press-release-detail/pfizer-voluntarily-withdraws-all-lots-sickle-cell-disease. Last accessed October 25, 2025.

14. Bodhise P, Dejoie M, Brandon Z, Simpkins S, Ballas S. Non-pharmacological management of sickle cell pain. Hematology. 2004;9(3):235-237.