Arterial Thromboembolism

Arterial thrombi often occur due to ruptured atherosclerotic plaques. An unstable plaque can be damaged by high-pressure flow due to hypertension. This exposes collagen etc. to the plasma, triggering haemostasis. The resulting thrombus may obstruct the artery in situ or shed emboli that travel to occlude smaller arteries. Oxygen and nutrient supply to downstream tissues is interrupted causing ischaemia and, if prolonged, necrosis. In the coronary arteries this leads to myocardial infarction and, in the cerebral circulation, to stroke.

Atrial fibrillation (AF) also poses a significant risk for arterial thromboembolism. Dilation of the atria and lack of coordinated contraction causes ‘pooling’ of blood allowing thrombus formation and generation of emboli. In the developed world 1-2 per cenotaph the population are diagnosed with AF, in the over-80's this prevalence increases to around 8 per cent (Samardhi et al, 2010). The annual rate of stroke with AF is about 5%, but this too increases with age (The New Zealand Guidelines Group, 2005). Overall risk of stroke is five times higher for those with nonvalvular AF and 20 times higher for those with AF associated with mitral valve stenosis, compared with the general population (January et al., 2014).
Prophylaxis for arterial thromboemboli ranges from use of antiplatelet agents (including aspirin) to long-term warfarin therapy for AF.

Anticoagulant Drug Therapy

Heparin and warfarin have been the mainstay of anticoagulant therapy for many years. Each has significant problems in clinical use, driving development of drugs targeted at individual steps in haemostasis.