Thrombosis
Thromboembolism is a leading cause of morbidity and mortality globally. Survival after VTE (venous thromboembolism including deep venous thrombosis and pulmonary embolism) is worse than the expected survival in age- and sex-matched controls [1, 2]. Moreover, the risk of death after a pulmonary embolism (PE) is 18-fold higher than after a deep vein thrombosis (DVT) [3]. VTE also poses a significant burden globally in terms of disability-adjusted life years (DALYs) lost in low-, middle-, and high-income countries [4]. In the year 2010, one in four deaths worldwide was attributed to arterial thromboembolic conditions (12.9 million deaths from arterial thromboembolic conditions compared to eight million deaths from cancer) [5]. These arterial thromboses primarily include myocardial infarction, ischemic strokes, and limb ischemia, whereas deep vein thrombosis and pulmonary embolism comprise the bulk of venous thrombosis. In 1856, Virchow described the three causes of thrombosis: blood hypercoagulability, stasis, and vessel wall abnormalities (Virchow’s triad). Blood components (including blood cells and plasma proteins) are the best studied of this triad, and the importance of alterations in pro- and anticoagulant proteins in the genesis of thrombosis is well established. In addition, the vessel wall is a major contributor to thrombosis risk and prevention. Its basic nature is antithrombotic, but with injury and inflammation, it turns into a prothrombotic organ. The vessel wall provides adhesion receptors that enable recruitment of leukocytes and platelets to sites of vascular injury and dysfunction. Upon injury, endothelium expresses tissue factor and exposes vascular smooth muscle tissue factor that is constitutively present. Additionally, vascular endothelial cells are constantly subjected to mechanical shear stress imposed by blood flow. Fluid shear stress itself through oscillatory and turbulent flow regulates vascular biology and pathology by ordering changes in protein expression via induction of vascular transcription factors. In this chapter we provide an overview of arterial and venous thrombosis. It will then focus on the pathogenesis of the complex and dynamic processes underlying venous and arterial thrombosis and the conditions that predispose to them. It will highlight disorders and pathogenetic markers to both. It aims to convey the concept that venous and arterial thrombosis forms a continuum with some features unique to each and others common to both.
