Sickle Cell Anemia

Sickle cell anemia is an inherited blood disorder characterized by abnormally shaped red blood cells (RBCs) caused by a defect in the hemoglobin molecule¹. Under normal conditions, hemoglobin efficiently transports oxygen throughout the body. However, in individuals with sickle cell anemia, hemoglobin molecules cluster together after releasing oxygen, causing the red blood cells to assume a rigid, sickle-like shape².These deformed cells become stiff and struggle to pass through small blood vessels, leading to vascular occlusion, ischemia, and tissue damage².

The disease was first described in 1919 by Dr. James Herrick, who reported a patient from the West Indies with anemia caused by sickle-shaped RBCs³. The genetic defect in the hemoglobin protein was later identified in 1956³.

Genetics and Cause

Sickle cell anemia is an autosomal recessive disorder, meaning that an individual must inherit two copies of the defective gene to develop the disease⁷.The mutation causes valine to replace glutamic acid in the hemoglobin molecule, altering the properties of red blood cells and increasing the likelihood of polymerization and sickling under low oxygen tension⁵.

If both parents carry the sickle cell trait:

• There is a 25% chance their child will inherit the disease.

• A 50% chance the child will be a carrier.

• And a 25% chance of being genetically unaffected⁹.

Epidemiology

Sickle cell anemia is most prevalent among individuals of African descent¹.In the United States, an estimated 50,000–70,000 people live with the disease, with approximately 1,000 new cases annually¹.In West and Central Africa, around 25% of the population carry the sickle cell trait, making it a widespread hereditary disorder⁵.

Clinical Presentation

Sickle cell anemia is an autosomal recessive disorder, meaning that an individual must inherit two copies of the defective gene to develop the disease⁷.The mutation causes valine to replace glutamic acid in the hemoglobin molecule, altering the properties of red blood cells and increasing the likelihood of polymerization and sickling under low oxygen tension⁵.

If both parents carry the sickle cell trait:

• There is a 25% chance their child will inherit the disease.

• A 50% chance the child will be a carrier.

• And a 25% chance of being genetically unaffected⁹.

Epidemiology

Sickle cell anemia is most prevalent among individuals of African descent¹.In the United States, an estimated 50,000–70,000 people live with the disease, with approximately 1,000 new cases annually¹.In West and Central Africa, around 25% of the population carry the sickle cell trait, making it a widespread hereditary disorder⁵.

Clinical Presentation

Symptoms vary greatly among patients but are primarily related to microvascular occlusion causing acute and chronic tissue damage⁷.Patients commonly experience painful crises lasting 5–6 days⁷.

Typical signs include:

• Anemia with fatigue, pallor, and irritability.

• Crises often triggered by physical exertion, infection, or temperature changes.

Pulmonary and Neurological Complications

Sickled cells may adhere to the lung endothelium, leading to inflammation and acute chest syndrome, characterized by chest pain, fever, cough, and shortness of breath⁵.Pulmonary hypertension and stroke are also common complications, especially among younger patients⁵.

Common Comorbidities

Sickle cell anemia is associated with multiple systemic complications⁵:

• Jaundice: Caused by excess bilirubin from rapid RBC destruction.

• Hand-foot syndrome: Blood clots in small vessels of the hands and feet cause pain, redness, and swelling.

• Splenic necrosis: The spleen is highly vulnerable to infarction, often leading to asplenia in childhood and increased infection risk⁸.

Systemic Involvement

System	Common Complications
Neurological	Seizures, stroke, meningitis
Pulmonary	Acute lung infarction, pneumonia, atelectasis, acute chest syndrome
Musculoskeletal	Avascular necrosis, osteomyelitis, hand-foot syndrome
Ocular	Retinopathy, blindness
Urogenital	Hematuria, nocturia, pregnancy complications
Dermatological	Stasis ulcers on hands, ankles, and feet
Other organs	Splenomegaly, hepatomegaly, gallstones

Treatment

There is no definitive cure for sickle cell anemia, but management focuses on symptom control and complication prevention⁵.

Key Management Strategies

• Pain management during crises

• Adequate hydration to prevent occlusion

• Infection prevention (vaccinations, prophylactic antibiotics)

• Regular organ function monitoring

• Hydroxyurea to increase fetal hemoglobin (HbF) and reduce crisis frequency

• Blood transfusions for severe anemia or stroke prevention

Differential Diagnoses

Conditions that may mimic sickle cell anemia⁵:

• Thalassemia

• Iron-deficiency anemia

• Autoimmune hemolytic anemia

• Other hemoglobinopathies

Diagnostic Tests and Laboratory Findings

In the United States, all newborns are routinely screened for sickle cell disease.Diagnosis is confirmed through:

• Sickle cell turbidity test detecting abnormal hemoglobin⁸

• Hemoglobin electrophoresis to differentiate hemoglobin types⁸

• Prenatal testing via amniocentesis (week 10) or chorionic villus sampling (week 16)⁵

Medical Management

Treatment aims to relieve symptoms, manage anemia, and prevent complications⁵.

Hydroxyurea is the cornerstone medication — it increases HbF production, enhances RBC flexibility, and reduces crisis frequency¹².

Pain Management Protocols

Pain Severity	Treatment Approach
Mild	Non-opioid analgesics ± adjuvants
Moderate	Weak opioid ± non-opioid ± adjuvants
Severe	Strong opioid ± non-opioid ± adjuvants¹³

Additional options:

• Blood transfusions (acute stroke or chest syndrome)

• Vasodilators/anticoagulants for pulmonary hypertension

• Fetal hemoglobin inducers (under investigation)

Genetic Counseling

Genetic counseling helps carrier couples understand:

• Inheritance patterns

• Disease risk in offspring

• Available reproductive options⁵

Bone Marrow Transplantation

Bone marrow transplantation is currently the only curative treatment. It restores normal RBC production and improves neurological and pulmonary outcomes⁵.Since the first successful case in 1984, studies show 78% disease-free survival at four years¹⁴.Challenges remain with graft rejection and GVHD, but newer techniques using facilitating cells show promising results¹⁵.

Physiotherapy and Rehabilitation

Physiotherapy can significantly enhance function and quality of life¹⁶.

Core Interventions

• Patient education: Importance of moderate physical activity

• Respiratory training: Breathing techniques and spirometry to prevent lung complications¹³

• Wound care: Management of stasis ulcers on limbs

• Stroke rehabilitation: Focus on strength, coordination, and neuromuscular recovery

• Hydrotherapy: Reduces pain frequency and improves respiratory function¹⁸

• Graded exercise: Gradual intensity increase with frequent breaks to prevent fatigue

• Modalities: Can be applied during crises, though evidence remains limited¹³

References:

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3. Brigham and Women’s Hospital. Brief History of Sickle Cell Disease. Harvard Medical School Research. 2002. http://sickle.bwh.harvard.edu/scd_history.html

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5. Goodman CC, Fuller KS. Pathology: Implications for the Physical Therapist. St. Louis; Saunders Elsevier: 2009.

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10. Pathology Student. Sickle Cell Anemia. 2009. http://www.pathologystudent.com/?p=310

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14. BMT for Sickle Cell Disease. Blood & Marrow Transplant Newsletter. 1998; 43(9). http://www.bmtinfonet.org/newsletters/issue43/sicklecell.html.

15. Ungar L. University of Louisville researcher may hold key to a cure for sickle cell disease. The Courier Journal 2010 Feb 21.: http://www.courier-journal.com/apps/pbcs.dll/article?AID=/201002210300/FEATURES03/2210306.

16. Stewart M. Sickle Cell Disorder and Physiotherapy. Physiotherapy. 1997; 83: 333-339.

17. Bernard TJ, Goldenberg NA, Armstrong WA et al. Treatment of Childhood Arterial Stroke. Annals of Neurology. 2008; 63: 679-696.

18. Tinti G, Somera R, Valente FM, Domingo CR. Benefits of kinesiotherapy and aquatic rehabilitation on sickle cell anemia: a case report. Genetics and Molecular Research. 2010; 9: 360-364.