title: 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, methylenetetra-hydrofolate 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.
authors.affiliation: a Division of Hematology/Oncology, Department of Pediatrics , Duke University Medical Center , Durham , NC 27710 , USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Zimmerman
authors.affiliation: a Division of Hematology/Oncology, Department of Pediatrics , Duke University Medical Center , Durham , NC 27710 , USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Howard
authors.affiliation: a Division of Hematology/Oncology, Department of Pediatrics , Duke University Medical Center , Durham , NC 27710 , USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Whorton
authors.affiliation: b Division of Hematology, Department of Medicine , Duke University Medical Center , Durham , NC 27710 , USA.
authors.forename: W F
authors.initials: WF
authors.lastname: Rosse
authors.affiliation: c Division of Maternal Fetal Medicine, Department of Obstetrics/Gynecology , Duke University Medical Center , Durham , NC 27710 , USA.
authors.forename: A H
authors.initials: AH
authors.lastname: James
authors.affiliation: a Division of Hematology/Oncology, Department of Pediatrics , Duke University Medical Center , Durham , NC 27710 , USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Ware
keywords: Avascular necrosis; Sickle cell anemia; Stroke; Thrombophilic mutations; Thrombosis