Sheep anti Human Protein S polyclonal antibody [HRP]

Venous thrombosis (VT) is a common multifactorial disease with a genetic component that was first suspected nearly 60 years ago. In this review, we document the genetic determinants of the disease, and update recent findings delivered by the application of high-throughput genotyping and sequencing technologies. To date, 17 genes have been robustly demonstrated to harbour genetic variations associated with VT risk: ABO, F2, F5, F9, F11, FGG, GP6, KNG1, PROC, PROCR, PROS1, SERPINC1, SLC44A2, STXBP5, THBD, TSPAN15 and VWF. The common polymorphisms are estimated to account only for a modest part (similar to 5 %) of the VT heritability. Much remains to be done to fully disentangle the exact genetic (and epigenetic) architecture of the disease. A large suite of powerful tools and research strategies can be deployed on the large collections of patients that have already been assembled (and additional are ongoing).

Background Protein S, which circulates in plasma in both free and bound forms, is an anticoagulant protein that stimulates activated protein C and tissue factor pathway inhibitor. Hereditary type I protein S deficiency (low total and low free protein S) is a well-established risk factor for venous thrombosis, whereas the thrombosis risk associated with type III deficiency (normal total and low free protein S) has been questioned. Design and Methods Kaplan-Meier analysis was performed on 242 individuals from 30 families with protein S deficiency. Subjects were classified as normal, or having type I or type III deficiency according to their total and free protein S levels. Genetic and functional studies were performed in 23 families (132 individuals). Results Thrombosis-free survival was not different between type I and type III protein S-deficient individuals. Type III deficient individuals were older and had higher protein S, tissue factor pathway inhibitor and prothrombin levels than type I deficient individuals. Thrombin generation assays sensitive to the activated protein C- and tissue factor pathway inhibitor-cofactor activities of protein S revealed similar hypercoagulable states in type I and type III protein S-deficient plasma. Twelve PROS1 mutations and two large deletions were identified in the genetically characterized families. Conclusions Not only type I, but also type III protein S deficiency is associated with a hypercoagulable state and increased risk of thrombosis. These findings may, however, be restricted to type III deficient individuals from families with mixed type I/III protein S deficiency, as these represented 80% of type III deficient individuals in our cohort.