PATHOPHYSIOLOGY

A β-hemoglobin gene mutation results in the synthesis of the sickle β-globin chain. Sickle hemoglobin (HbS) polymerizes when deoxygenated, and polymer-associated injury to the sickle erythrocyte is the proximate cause of sickle cell disease. The principal pathophysiological features of this disease are shown in the figure and can be grouped as vasoocclusive/blood viscosity related and hemolysis/vasculopathy related. This complex pathophysiology involves diverse molecular and cellular defects that include abnormal erythrocyte volume regulation, impaired nitric oxide bioavailability, reperfusion injury and inflammation, altered hemostasis, defects of intercellular interactions, endothelial cell damage, leukocyte and platelet activation, and in all probability, other perturbations of normal physiology.

DIAGNOSIS

Sickle cell disease is a constellation of similar but not identical disorders, all of which have at least 50% HbS in the blood. The phenotype of sickle cell disease is caused by several common and some less common genotypes; homozygotes for the HbS gene are said to have sickle cell anemia; common compound heterozygous forms of disease include HbSC disease and HbS-β thalassemia. The cornerstone of the clinical laboratory diagnosis is the detection and quantification of HbS. Depending on the context of the diagnostic situation, direct detection of the HbS and other globin gene mutations can be warranted. Sickle cell trait is clinically benign and not considered a form of sickle cell disease.

CLINICAL FEATURES

The complications of sickle cell disease can occur acutely, producing dramatic clinical findings, or they can be chronic, disabling, and cause premature death.