Basic mechanisms and pathogenesis of venous thrombosis

Abstract

In 1856 Virchow proposed a triad of causes for venous thrombosis, postulating that stasis, changes in the vessel wall or changes in the blood could lead to thrombosis. We now know that abnormally high levels of some coagulation factors and defects in the natural anticoagulants contribute to thrombotic risk. Among these, factor V Leiden, which renders factor Va resistant to activated protein C, is the most prevalent with approximately 5% of the Caucasian population having this genetic alteration. These genetically controlled variants in coagulation factors work in concert with other risk factors, such as oral contraceptive use, to dramatically increase thrombotic risk. While these abnormalities in the blood coagulation proteins are associated with thrombotic disease propensity, they are less frequent contributors to thrombosis than age or cancer. Cancer increases thrombotic risk by producing tissue factor to initiate coagulation, by shedding procoagulant lipid microparticles or by impairing blood flow. Age is the strongest risk factor for thrombosis. Among possible reasons are fragility of the vessels potentially contributing to stasis, increased coagulation factor levels, impaired function of the venous valves, decreases in the efficacy of natural anticoagulants associated with the vessel wall, increased risk of immobilization and increased risk of severe infection.

Extracellular DNA traps promote thrombosis

“…Red thrombi, as well as leukocyte recruitment, are characteristics of DVT (6). Thus, we investigated whether NETs are formed in experimental DVT in baboons.…”

“…Thrombus formation can be enhanced by inflammation and endothelial dysfunction (4). Deep vein thrombosis (DVT), which affects over 375,000 patients per year in the United States (5), is often linked to inflammation (6) and infections (7).…”

The relation between soluble endothelial protein C receptor and factor VIII levels and FVIII/sEPCR index in healthy infants

“…Various genetic and environmental conditions have been discussed as risk factors for thrombotic events in adult and pediatric patients [19]. Functional polymorphisms in the EPCR gene may increase/decrease the risk of thrombosis, especially in carriers of prothrombotic mutations [20].…”

Methylenetetrahydrofolate Reductase (MTHFR C677T) Polymorphism in Sudanese Patients with Deep Vein Thrombosis

“…However, it is clear that the mechanisms initiating the venous thrombosis are very different from those initiating the arterial thrombosis [4]. Thrombus formation and propagation depend on the presence of abnormalities of blood flow, blood vessel wall, and blood clotting components, known collectively as Virchow triad [5]. Endothelial imbalance may possibly play an important role [6].…”