Sickle cell disease causes painful crises due to vaso-occlusion of small blood vessels (vaso-occlusive crisis). The primary cause of the clinical phenotype of SCD is the intracellular polymerization of sickle hemoglobin resulting in sickling of red blood cells (RBCs) in deoxygenated conditions. Deoxygenated RBCs containing predominantly HbS develop a sickle or crescent shape, and become inflexible, increase blood viscosity, and block or limit blood flow within limbs or organs. The process is further aggravated by abnormal interactions of these RBCs with leukocytes, platelets, vascular endothelium, and clotting factors thus causing acute and chronic complications. The frequency and severity of complications can be reduced with hydroxyurea or blood transfusion therapy. However, both treatments are currently underutilized.

Transfusion support remains a key intervention in the management of patients with sickle cell disease (SCD). Red cell transfusions are used in the acute and chronic management of many complications related to SCD, but are not without adverse effects, including alloimmunization and iron overload (hemochromatosis).

Prevention

Children with SCD should receive routine preventive care and immunizations recommended by the National Authorities. Persons with SCD also benefit from specialized condition-specific preventive strategies. Children with SCD are at increased risk of invasive pneumococcal disease. Therefore, in addition to the recommended pneumococcal vaccinations for all infants and children, those with SCD should receive prophylactic oral penicillin once the diagnosis is established; this regimen should be continued until at least the age of five years.

Persons with SCD are at increased risk of vascular complications, particularly stroke. Persons with SCD should be screened regularly with transcranial Doppler ultrasonography (TCD) beginning in childhood (age 2 years). TCD measures and reports the average velocity of blood flow through the internal carotid and proximal middle cerebral arteries. When TCD findings are marginal or conditional (170 to 199 cm per second) or elevated (200 cm per second or greater), the child is considered a candidate for blood transfusion therapy to prevent stroke and should be referred for co-management with a subspecialist. Although the incidence of strokes is higher in patients with the Hb SS and Hb S/ß0 thalassemia genotype, it should be noted that strokes also occur in patients with other genotypes.

Screening for ischemic retinopathy

Refer patients with SCD to an ophthalmologist for an annual dilated retinal examination beginning at 10 years of age. Rescreen persons with normal dilated retinal examination findings at 1- to 2-year intervals.

Screening for renal disease 

Begin annual screening of persons with SCD for microalbuminuria and proteinuria with spot urine testing by 10 years of age. Refer persons with proteinuria to a nephrologist for further evaluation.

Persons with SCD can have acute complications that require rapid interventions to avert or lessen the risk of life-threatening consequences.