Sickle Cell Disease : Definition, Pathophysiology, Diagnosis And Treatment
Sickle cell syndromes are hereditary disorders characterized by the presence of sickle hemoglobin (HbS) in red blood cells (RBCs).
Pathophysiology of Sickle Cell Disease :
- The most common abnormal hemoglobin in the United States is hemoglobin S. Two genes for hemoglobin S (HbSS) result in sickle cell disease or sickle cell anemia, which occurs in 0.3% of African Americans. One gene for hemoglobin S (HbS) results in sickle cell trait, which occurs in 8% of African Americans. Hemoglobin C, another abnormality, occurs in 2% to 3% of African Americans.
- Pathology is more likely to occur with HbSS but can occur with HbS, especially if it coexists with hemoglobin C or thalassemia.
- The clinical manifestations of sickle cell disease are attributable to impaired circulation, RBC destruction, and stasis of blood flow. These problems are attributable to disturbances in RBC polymerization and to membrane damage.
- Polymerization allows deoxygenated hemoglobin to exist as a semisolid gel that protrudes into the cell membrane, distorting RBCs into sickle shapes. Sickle-shaped RBCs increase blood viscosity and encourage sludging in the capillaries and small vessels. Such obstructive events lead to local tissue hypoxia and accentuate the pathologic process.
- Repeated cycles of sickling, upon deoxygenation, and unsickling, upon oxygenation, damage the RBC membrane and cause irreversible sickling. Rigid, sickled RBCs are easily trapped, shortening their circulatory survival and resulting in chronic hemolysis.
- Additional contributing factors include functional asplenia (and increased risk of bacterial infection), deficient opsonization, and coagulation abnormalities.
Clinical Features of Sickle Cell Trait and Common Sickle Cell Disease :
- Sickle cell trait (SCT) : Rare painless hematuria; normal Hgb level; heavy exercise under extreme conditions may provoke gross hematuria and complications
- Sickle cell anemia (SCA) : Pain crises, microvascular disruption of organs (spleen, liver, bone marrow, kidney, brain, and lung), gallstone, priapism, leg ulcers, anemia (Hgb 7-10 g/dL)
- Sickle hemoglobin C : Painless hematuria and rare aseptic necrosis of bone; vaso-occlusive crises are less common and occur later in life; other complications are ocular disease and pregnancy-related problems; mild anemia (Hgb 10-12 g/dL)
- Sickle Î²+-thalassemia : Rare crises; milder severity than sickle cell disease because of production of HbA; Hgb 10-14 g/dL with microcytosis
- Sickle Î²Â°-thalassemia : No HbA production; severity similar to SCA; Hgb 7-10 g/dL with microcytosis
Diagnosis of Sickle Cell Disease :
- Sickle cell disease is usually identified by routine neonatal screening programs using isoelectric focusing.
- Laboratory findings include low hemoglobin; increased reticulocyte, platelet, and leukocyte counts; and sickle forms on the peripheral smear.
Treatment of Sickle Cell Disease :
- Patients with sickle cell disease require lifelong multidisciplinary care. Interventions include general measures, preventive strategies, and treatment of complications and acute crises.
- Patients with sickle cell disease should receive routine immunizations plus influenza, meningococcal, and pneumococcal vaccinations.
- Prophylactic penicillin is recommended for children with sickle cell disease until they are 5 years old. The dosage is penicillin V potassium, 125 mg orally twice daily until 3 years of age and then 250 mg twice daily, or benzathine penicillin, 600,000 units intramuscularly every 4 weeks.
- Folic acid, 1 mg daily, is recommended in adult patients, pregnant women, and patients of all ages with chronic hemolysis.
- Patients should be educated to recognize conditions that require urgent evaluation. To avoid exacerbation during acute illness, patients should maintain balanced fluid status and oxygen saturation of at least 92%.
- RBC transfusions are indicated for acute exacerbation of baseline anemia (e.g., aplastic crisis, hepatic or splenic sequestration, severe hemolysis), severe vasoocclusive episodes, and procedures requiring general anesthesia or ionic contrast. Transfusions might be beneficial in patients with complicated obstetric problems, refractory leg ulcers, refractory and protracted painful episodes, and severe priapism.
- Fever of 38.5Â°C or higher should be evaluated promptly. A low threshold for empiric antibiotic therapy with coverage against encapsulated organisms is recommended (e.g., ceftriaxone for outpatients and cefotaxime for inpatients).
- Patients with acute chest syndrome should receive incentive spirometry; appropriate fluid therapy; broad-spectrum antibiotics including a macrolide or quinolone; and, for hypoxia or acute distress, oxygen therapy. Steroids and nitric oxide are being evaluated.
- Priapism has been treated with analgesics, antianxiety agents, vasoconstrictors to force blood out of the corpus cavernosum (e.g., phenylephrine, epinephrine), and vasodilators to relax smooth muscle (e.g., terbutaline, hydralazine).
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