Importantly, there is a dramatic increase in the risk of VTE above the age of 50, and it reaches as high as 1 in every 100 individuals yearly (3). (VTE) (2). The incidence of VTE in industrialized countries is definitely 1C3 individuals per 1,000 per year (3C8). Importantly, there is a dramatic increase in the risk of VTE above the age of 50, and it reaches as high as 1 in every 100 individuals yearly (3). These alarming statistics led the US Senate to designate March as DVT Consciousness Month in 2005 and the Doctor Generals call to action to prevent DVT and PE in 2008. There are several genetic and acquired risk factors that are associated with VTE and recurrent VTE (examined in refs. 8C11). Strong genetic risk factors that lead to a hypercoagulable state include deficiencies in the anticoagulants antithrombin, protein C, and protein S. Moderate genetic risk factors include element V (FV) Leiden, prothrombin G20210A, fibrinogen C10034T and nonCtype O blood. FV Leiden is present in approximately 5% of people of mixed Western descent and is a variant of FV that is resistant to inactivation by triggered protein C. Prothrombin G20210A is definitely solitary nucleotide polymorphism in the 3 untranslated region of the prothrombin gene that leads to improved manifestation. Fibrinogen C10034T is definitely a fibrinogen gamma-chain gene variant that leads to reduced levels of the on the other hand spliced form of the fibrinogen gamma-chain that is associated with improved venous thrombosis (8). Finally, individuals with nonCtype O blood have improved clearance of von Willebrand element (vWF). Since FVIII circulates in plasma bound to vWF, a reduction in plasma vWF is also associated with reduced levels of FVIII. Acquired risk factors include age, surgery treatment, obesity, cancer, pregnancy, hormone-based contraceptives, hormone alternative, antiphospholipid syndrome, acute illness, immobilization, paralysis, long-haul travel, smoking, hospitalization, reduced fibrinolysis, and acquired thrombophilia Rabbit polyclonal to RAB18 (improved levels of procoagulant factors and/or decreased levels of anticoagulant factors) (12C30). Obesity has a high prevalence in the US and Western countries (15, 25, 29), and one study showed that obesity (body mass index 30 kg/m2) improved the risk of thrombosis 2 collapse (25). Another study analyzed the risk associated with oral contraceptives with or without FV Leiden and found that the incidence of thrombosis was improved 4 collapse in individuals taking hormone contraceptives, 7 collapse in those with FV Leiden, and 36 collapse in individuals with both risk factors (24). This study shown impressive synergy of these risk factors. A VTE risk rating model has been founded for ambulatory individuals with cancer based on 5 guidelines (tumor site, leukocyte count, platelet count, body mass index, and either low hemoglobin and/or use of erythropoiesis-stimulating providers) (31). Symptomatic VTE was observed in 0.6% of patients with a score of 0 compared with 6.9% of patients with a score of 3 or higher. A recent study extended this scoring system to include the biomarkers D-dimer and P-selectin and found that patients with the highest score experienced a cumulative VTE probability after 6 months of 35% compared with a probability of 1% for those patients with the lowest score (32). Clot formation A blood clot contains a mixture of platelets and fibrin and in some cases red blood cells (1, 33). Importantly, the etiologies of XMU-MP-1 arterial and venous clots are very different (1). Arterial clots are created under high shear stress, typically after rupture of an atherosclerotic plaque or other damage to the blood vessel wall (34C36). They are platelet-rich (so called white clots) and are generally treated with antiplatelet drugs. In contrast, venous clots form under lower shear stress on the surface of a largely intact endothelium (36C39). They are fibrin-rich (so called reddish clots because they also contain red blood XMU-MP-1 cells) and are treated with anticoagulant drugs. The blood coagulation cascade can be divided into three parts: the extrinsic, intrinsic, and common pathways (Physique ?(Physique11 and reviewed XMU-MP-1 in refs. 39C42). Under pathological conditions, tissue factor (TF) is expressed on circulating leukocytes and possibly activated endothelial cells (40). In addition, TF is present on microvesicles (MVs), which are XMU-MP-1 small membrane vesicles released from activated cells (43C45). These intravascular sources of TF may trigger the formation of venous clots. Recent studies have shown that FXII can be activated by extracellular RNA and polyphosphates and this activation of the.