Thrombophilic DNA mutations as independent risk factors for stroke and avascular necrosis in sickle cell anemia

Abstract

Thrombosis may be important in the pathophysiology of certain complications of sickle cell anemia (SCA), including cerebrovascular accident (CVA, stroke) and avascular necrosis (AVN). No single laboratory or clinical parameter can accurately identify patients who will develop these thrombotic complications. We hypothesized that a subset of patients with SCA have genetic thrombophilic mutations that increase the risk of stroke or AVN. We examined nine known thrombophilic DNA polymorphisms in α-fibrinogen, β-fibrinogen, platelet glycoprotein IIIa, Factor VII, methylenetetrahydrofolate reductase, plasminogen activator inhibitor-1, prothrombin, and Factor V genes in 101 African-American patients with SCA (27 CVA, 16 AVN). The allele frequency of thrombophilic mutations ranged from 0.0 (Prothrombin, Factor V) to 0.33 (α-fibrinogen). No mutation was significantly more common in patients with CVA or AVN than in patients without these complications. These nine thrombophilic mutations do not appear to be significant risk factors for the development of clinically overt CVA or AVN in SCA.