Homozygous Factor V Leiden mutation in sickle cell anaemia.
- SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: Hemoglobin S in homozygous state or in combination with one of the structural variants of Hb D-Punjab, Hb O-Arab, Hb C or β-thalassemia mutation results in sickle cell disease (SCD) that is characterized by chronic hemolytic anemia and tissue injury secondary to vasooclusion. A chronic hypercoagulable state in SCD has been established with the increased risk of thromboembolic complications in these patients. The goal of present review is to survey of the literature related to thromboembolic events and genetic risk factors involved in the manifestation of these events in SCD patients with focus on studies from Mediterranean countries. Also, this review covers the pathogenesis of hypercoagulability and alteration in the components of hemostasis system.Mediterranean Journal of Hematology and Infectious Diseases 05/2011; 3(1):e2011024. DOI:10.4084/MJHID.2011.024
- [Show abstract] [Hide abstract]
ABSTRACT: Vaso-occlusion is a determinant for most signs and symptoms of sickle-cell anemia (SCA). The mechanisms involved in the pathogenesis of vascular complications in SCA remain unclear. It is known that genetic polymorphisms associated with thrombophilia may be potential modifiers of clinical features of SCA. The genetic polymorphisms C677T and A1298C relating to the enzyme methylenetetrahydrofolate reductase (MTHFR), a clotting Factor V Leiden mutation (1691G→A substitution of Factor V Leiden), and the mutant prothrombin 20210A allele were analyzed in this study. The aim was to find possible correlations with vascular complications and thrombophilia markers in a group of SCA patients in Pernambuco, Brazil. The study included 277 SCA patients, divided into two groups: one consisting of 177 nonconsanguineous SCA patients who presented vascular manifestations of stroke, avascular necrosis, leg ulcers, priapism, and acute chest syndrome (group 1); and the other consisting of 100 SCA patients without any reported vascular complication (group 2). Molecular tests were done using either polymerase chain reaction (PCR) restriction fragment length polymorphism or allele-specific PCR techniques. Comparisons between the groups were made using the χ(2) test. The 677 CT and TT genotypes showed a significant risk of vascular complications (p=0.015). No significant associations between the groups were found when samples were analyzed for the MTHFR A1298C allele (p=0.913), Factor V G1691 (p=0.555), or prothrombin G20210A mutation (p=1.000). The polymorphism MTHFR C677T seemed to be possibly predictive for the development of some vascular complications in SCA patients among this population.Genetic Testing and Molecular Biomarkers 08/2012; 16(9):1038-43. DOI:10.1089/gtmb.2011.0361 · 1.15 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Recent studies suggest that sickle cell disease (SCD) is a hypercoagulable state contributing to vaso-occlusive events in the microcirculation, resulting in acute and chronic sickle cell-related organ damage. In this article, we review the existing evidence for contribution of hemostatic system perturbation to SCD pathophysiology. We also review the data showing increased risk of thromboembolic events, particularly newer information on the incidence of venous thromboembolism. Finally, the potential role of platelet inhibitors and anticoagulants in SCD is briefly reviewed.Hematology/oncology clinics of North America 04/2014; 28(2):355-374. DOI:10.1016/j.hoc.2013.11.011 · 2.07 Impact Factor