The genetics of venous and arterial thromboembolism

Abstract

There is substantial evidence to indicate that the pathologic processes of venous and arterial thromboembolism involve both genetic and environmental influences. Scientific progress over the past decade has revealed a growing number of genetic factors, such as factor V Leiden and the prothrombin gene variant, that are present in more than 1% of the population and increase the relative risk of venous thrombosis between two- and sevenfold. Furthermore, several of these factors have been demonstrated to interact adversely with environmental influences, such as oral contraceptives and smoking. Although these traits are present at relatively high prevalence in the population, the magnitude of the increased thrombotic risk associated with these factors is substantially less than that related to inherited deficiency of the natural anticoagulant protein antithrombin, and somewhat less than the elevated risk with protein C and protein S deficiencies. In contrast to the progress that has been made in understanding the genetic contributions to venous thromboembolism, much still remains to be learned about the genetic basis of arterial thrombosis. Despite the documentation of associations between several genetic polymorphisms with plasma procoagulant levels, consistent associations with arterial thrombotic disease have not been found.

Factor V: a combination of Dr Jekyll and Mr Hyde

“…133,134 No correlation has been observed between arterial thrombosis and the existence of factor V LEIDEN . [135][136][137] The frequency of factor V LEIDEN in patients with arterial thrombi is approximately 5%, a value similar to the frequency of the mutation present in the normal population. An explanation for this phenomenon is potentially found in the composition of the clot.…”

ACC/AHA 2005 Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic): A Collaborative Report from the American Association for Vascular Surgery/Society for Vascular Surgery,⁎Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients

“…Thromboembolic arterial occlusive disease affects both large (macroembolic) and small (microembolic) vessels (25)(26)(27)(28)(29). Macroemboli usually originate from a cardiac source (such as thrombus in the left atrial appendage, atrial fibrillation, ventricular thrombus secondary to MI or heart failure), whereas microemboli may have either a cardiac source (typically a diseased native valve or a thrombogenic prosthetic valve) or an arterial source (most often a ruptured cholesterol-containing plaque that produces distal atheroembolization).…”

“…‡Based on a random-effects meta-analysis of the results from various sources, each weighted with the inverse of the variance(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). §Based on a random-effects meta-regression analysis of the results from various sources, each weighted with the inverse of the variance(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46).Reprinted from Kandarpa K, Becker, BJ, Hunink, M, et al J Vasc Interv Radiol 2001;12:683-95 (438a). Hirsch et al 2005 ACC/AHA Practice Guidelines treated with either technique…”

ACC/AHA 2005 Practice Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic)

“…‡Based on a random-effects meta-analysis of the results from various sources, each weighted with the inverse of the variance (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). §Based on a random-effects meta-regression analysis of the results from various sources, each weighted with the inverse of the variance (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46) (448). The trials of Holm et al (448) and Wolfe et al (446) both excluded patients with long-segment disease (greater than 6 cm and greater than 10 cm, respectively).…”