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CPB as well as surgical trauma have a significant impact on the usually well-balanced coagulation system. This often leads to bleeding complications, and interventions to restore this balance are frequently attempted perioperatively. The coagulation and inflammatory systems are so complex that restoration of homeostatic balance cannot be achieved by giving blood products alone. Major known causes of CPB associated coagulopathy are dilution, complex and variable platelet dysfunction, fibrinolysis, the effects of heparin and protamine, hypocalcemia, hypothermia, as well as activation of the coagulation system after contact with artificial surfaces and from tissue factor release from the endothelium in response to ischemia and reperfusion.
Long-term (>1 year) single antiplatelet therapy with aspirin is effective in reducing the risk of any early recurrent stroke by about one-sixth compared with no antiplatelet therapy. Clopidogrel monotherapy is marginally but significantly more effective than aspirin in reducing major vascular events. Cilostazol is also more effective than aspirin in Asian patients, and its therapeutic efficacy may be augmented by the addition of probucol in patients with ischaemic stroke and high risk of cerebral haemorrhage. The safety and effectiveness of cilostazol in non-Asian patients is not known. Prasugrel monotherapy (3.75 mg daily) is not non-inferior to clopidogrel monotherapy among Japanese patients with non-cardioembolic ischaemic stroke. Dual antiplatelet therapy with aspirin and extended-release dipyridamole is more effective than aspirin monotherapy and equally effective as clopidogrel monotherapy in preventing recurrent stroke. Dual antiplatelet therapy with aspirin and clopidogrel is more effective than aspirin monotherapy in preventing recurrent ischaemic stroke and myocardial infarction in high vascular risk patients, but it also increases the risk of major bleeding which may offset its benefits. Dual antiplatelet therapy with cilostazol added to aspirin or clopidogrel is more effective, and as safe as, aspirin or clopidogrel monotherapy in Japanese patients with non-cardioembolic ischaemic stroke.
Aspirin 160–300 mg daily started within 48 h of onset of acute ischaemic stroke is associated with a small beneficial reduction in recurrent ischaemic stroke (6 fewer per 1000 patients treated) and pulmonary embolism (1.5 fewer per 1000) that outweighs increased risk of bleeding (2 extra symptomatic ICHs and 4 extra major extracranial haemorrhages). The net effect is that, for every 1000 patients treated early with aspirin, 22 have reduced long-term disability, including 11 more achieving full recovery. Only two single antiplatelet regimens have been compared head to head against aspirin alone: cilostazol (a phosphodiesterase inhibitor) performed similarly to aspirin; ticagrelor (a GP IIa/IIIb receptor antagonist) showed tended to reduce ischaemic events but increased minor bleeding and dyspnea. In minor, non-cardioembolic ischaemic stroke or TIA, early dual antiplatelet therapy (DAPT) has shown advantages over early monotherapy. Most well-studied is clopidogrel and aspirin, with similar findings for dipyridamole and aspirin. DAPT reduces all-type (ischaemic and haemorrhagic) recurrent stroke (27 fewer per 1000 treated patients), but minimally increases major extracranial bleedings (3 more per 1000). Confining DAPT to the first 3 w maximizes the benefit to harm ratio. Anticoagulants alone and arterial-dose anticoagulants added to antiplatelet agents offer no net advantages over antiplatelet drugs alone. Venous prophylaxis-dose anticoagulants and aspirin, compared with aspirin alone, reduced recurrent ischaemic stroke more than it tend increased major extracranial haemorrhage.
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