Sickle Cell Disease

Basics

DESCRIPTION

Sickle cell disease (SCD) is a disease caused by a homozygous inheritance of a one base pair change leading to an amino acid change in the beta globin gene at the sixth position: glutamic acid to valine on chromosome 11. The mutation leads to undesired polymerization of hemoglobin in the red cell causing membrane distortion which has systemic effects on the host.

EPIDEMIOLOGY

The incidence of SCD is 1 in 500 African Americans, 1 in 36,000 Hispanics, with a lesser frequency in other ethnic groups. The incidence of sickle cell trait (SCT) in African Americans is 1 in 14.
There are 70,000 to 100,000 affected individuals with SCD in the United States.

RISK-FACTORS

GENETICS

SCD is autosomal recessive.
The disease can be caused by homozygous inheritance of beta globin with the S mutation or by inheriting the mutated beta globin S with an additional beta globin mutation such as abnormal beta globin causing hemoglobin C, beta thalassemia, or D^{Los Angeles}, and O^Arab.

PATHOPHYSIOLOGY

Membrane distortion caused by this abnormal hemoglobin leads to: increased adhesion to vascular endothelium, activation of cytokines leading to activation of platelets and leukocytes, and ultimately to vaso-occlusion.
Extravascular hemolysis causes release of free hemoglobin and subsequent oxidative stress causing vasoconstriction, inflammation and platelet activation.

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