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Venous thromboembolism


Anticoagulation in venous thromboembolism


The balance between optimal efficacy and maximal safety has fuelled the search for new anticoagulant drugs for the treatment of venous thromboembolism, a frequent and serious condition


Thomas Vanassche MD PhD Peter Verhamme MD PhD Vascular Medicine and Haemostasis, University Hospitals Leuven, Belgium


Venous thromboembolism (VTE) is a spectrum of diseases caused by the formation of blood clots, or thrombi, in the veins. These thrombi can manifest in different ways, ranging from very acute to more insidious, and from asymptomatic to lethal.


The most common presentation is deep vein thrombosis (DVT) of the legs (Figure 1). Partial or complete blockage of the venous blood flow can cause swelling and pain of the affected leg. In rare cases, massive venous congestion can compromise arterial blood flow, causing limb-threatening ischaemia. Besides these acute symptoms, DVT can give rise to a chronic condition known as post-thrombotic syndrome, characterised by recurrent or permanent swelling and pain due to venous insufficiency.


The most severe manifestation of VTE is pulmonary embolism (PE) (Figure 2). In PE, thrombus fragments from a DVT dislocate and move through the venous system to the right heart, into the pulmonary circulation. Small emboli may cause no or only limited symptoms, typically chest pain, cough, and shortness of breath. However, when larger parts of the pulmonary circulation are blocked, PE can lead to respiratory and circulatory failure, and even death. Long-term complications of PE include right heart failure and pulmonary hypertension due to the increased resistance of the lung vasculature.


Other, less frequent, manifestations of Intrinsic pathway Extrinsic pathway


XI


TF


IX X VIII II V


VII


Fibrin clot DVT PE


When blood comes into contact with damaged vessels, the high concentration of tissue factor (TF) activates factor VII through the extrinsic pathway of anticoagulation. Alternatively, activation of factor XII to factor XIIa by foreign surfaces triggers the stepwise activation of factor XI, factor IX, and factor X via the intrinsic pathway.Factor X constitutes the start of the common pathway, leading to the conversion of prothrombin into active thrombin (factor II). Thrombin activates factor V and factor VIII, which activate positive feedback loops that further amplify thrombin activity. When a sufficiently strong burst of thrombin generation occurs, fibrin strands are formed, resulting in a blood clot. Pathological clot formation inside veins leads to deep vein thrombosis (DVT). DVT in turn can cause pulmonary embolism (PE) when clot fragments dissociate and embolise to the pulmonary circulation.


Figure 1: The coagulation cascade and the pathophysiology of VTE


VTE include upper limb DVT, and venous thrombosis in unusual sites such as pelvic or splanchnic veins, and cerebral sinus.


Incidence of VTE


VTE is a frequent disorder; with an overall annual incidence of 1–2 per 1000


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