Anticoagulant-associated hemorrhage

Overall no evidence was found to support the claim that anticoagulants offer a net advantage over aspirin in patients with acute ischemic stroke. There was evidence, however, to suggest that combination anticoagulant and aspirin therapy was associated with a small increase in the number of deaths at the end of follow-up, equivalent to 20 more deaths per 1000 patients treated. This adverse effect can probably be attributed partly to the 10 extra sICHs, and the 5 extra major extracranial hemorrhages per 1000 patients treated with combination anticoagulant/ aspirin therapy. 

Some of the association between atrial fibrillation and stroke must be coincidental because atrial fibrillation can be caused by coronary and hypertensive heart disease, both of which may be associated with atheromatous disease or primary intracerebral hemorrhage. Although anticoagulation markedly reduces the risk of first or recurrent stroke, this is not necessarily evidence for causality because this treatment may be working in other ways, such as by inhibiting artery-to-artery embolism, although trials of warfarin in secondary prevention of stroke in sinus rhythm have shown no benefit over aspirin (Ch. 24). 

Primary intracerebral hemorrhage is more common than subarachnoid hemorrhage, and its incidence increases with age (see Fig. 1.1). It is more frequent in Southeast Asian, Japanese and Chinese populations than in whites. The most common causes are intracranial small vessel disease, which is associated with hypertension, cerebral amyloid angiopathy and intracranial vascular malformations (Sutherland and Auer 2006). Rarer causes include saccular aneurysms, hemostatic defects, particularly those induced by anticoagulation or therapeutic thrombolysis, antiplatelet drugs, infective endocarditis, cerebral vasculitis and recreational drug use (Neiman et al. 2000 O Connor et al. 2005). 

The few pathological data available indicate that cerebral microbleeds are small areas of old hemorrhage, often associated with lipohyalinosis in the deep perforating arteries feeding the affected area of the brain (Fazekas et al. 1999). It is unclear whether the presence of microbleeds increases the risk of intracerebral hemorrhage in patients treated with antiplatelet or anticoagulant therapy (Cordonnier et al. 2007) although they seem not to be associated with increased risk in thrombolysis (Ch. 11). 

The most widely prescribed anticoagulant in North American is warfarin sodium (Coumadin). It was discovered serendipitously in the early 1940s at the University of Wisconsin after hemorrhagic deaths occurred in cattle eating spoiled sweet clover. Warfarin is approved by the FDA for the prevention and treatment of VTE as well as for the prevention of thromboembolic complications associated with atrial fibrillation, heart valve replacement, and myocardial infarction. Because of its narrow therapeutic index, predisposition to drug and food interactions, and propensity to cause hemorrhage, warfarin requires... 

---