Genetic variations in sites of affinity between FVIII and LRP1 are not associated with high FVIII levels in venous thromboembolism
نویسندگان
چکیده
Increased factor VIII (FVIII) levels are a prevalent and independent risk factor for venous thromboembolism (VTE). The low density lipoprotein receptor-related protein 1 (LRP1) has been associated with FVIII catabolism. After a median of 10 years of the first thrombotic episode, we evaluated FVIII activity levels in 75 patients with VTE and high FVIII levels and in 74 healthy controls. Subsequently, we evaluated the regions of F8 and LRP1 genes coding sites of affinity between these proteins, with the objective of determining genetic alterations associated with plasma FVIII levels. After a median time of 10 years after the VTE episode, FVIII levels were significantly higher in patients when compared to controls (158.6 IU/dL vs. 125.8 IU/dL; P ≤ 0.001]. Despite the fact that we found 14 genetic variations in F8 and LRP1 genes, no relationship was found between FVIII levels with these variations. We demonstrated a persistent increase of FVIII levels in patients with VTE, but in a much lower magnitude after 10 years when compared to 3-years after the episode. Moreover, we observed no relationship of genetic variations in the gene regions coding affinity sites between LRP1 and FVIII with FVIII levels.
منابع مشابه
High factor VIII levels in venous thromboembolism show linkage to imprinted loci on chromosomes 5 and 11.
High factor VIII (FVIII) levels are known to be a risk factor for deep venous thrombosis, but the mechanisms responsible for high FVIII levels remain unclear. Here, a new phenotype "FVIII level residuum" (FVIII-R) was defined in order to eliminate the impact of common determinants on FVIII levels. We studied 13 families of patients with thrombosis and reproducibly high FVIII levels of unknown o...
متن کاملHigh factor VIII, von Willebrand factor, and fibrinogen levels and risk of venous thromboembolism in blacks and whites.
Venous thromboembolism (VTE) affects more than 300,000 people in the United States each year. However, it has been estimated that current diagnostic testing fails to identify prothrombotic risk in 50% of VTE patients. This article examines the relationship between levels of the pro-coagulant proteins factor VIII (FVIII), von Willebrand factor (VWF), and fibrinogen and risk of VTE in order to as...
متن کاملBlood Coagulation, Fibrinolysis and Cellular Haemostasis Introduction
A high plasma concentration of coagulation factor VIII (FVIII) is an important risk factor for venous thromboembolism (VTE) (1-4). In the Leiden Thrombophilia study for example, FVIII levels above 1500 IU/L conferred an almost 5-fold risk for a first episode of deep-vein thrombosis (1). Most importantly, high FVIII is also associated with a very high risk of recurrent venous thromboembolism (4,...
متن کاملBeta 2 adrenergic receptor polymorphisms: association with factor VIII and von Willebrand factor levels and the risk of venous thrombosis.
Several studies have shown that elevated plasma levels of coagulation factor VIII (FVIII) are a risk factor of venous thrombosis. This risk remained after correction for the main determinants of FVIII levels, blood group and vonWillebrand factor (VWF) [1–3]. FVIII activity levels (FVIII:C) ‡150 IU dL increase the risk of a first venous thrombosis fivefold when compared to levels >100 IU dL. The...
متن کاملHigh factor VIII levels independently predict venous thromboembolism in cancer patients: the cancer and thrombosis study.
OBJECTIVE Patients with cancer are at an increased risk for venous thromboembolism (VTE). Clotting factor VIII activity (FVIII) has been established as risk factor of primary and recurrent VTE. We investigated FVIII as predictive parameter of VTE in cancer patients. METHODS AND RESULTS The prospective observational Cancer and Thrombosis Study (CATS) includes patients with newly diagnosed canc...
متن کامل