Oral
anticoagulant therapy is very effective in preventing
thromboembolism. Its major complication is
hemorrhage. The rate of intracranial
bleeding from randomized trials and observational studies ranges from 0.1 to 0.9% per year and largely depends on the International Normalized Ratio (INR) target range. Risk factors for this often-fatal complication include INR intensity, older age,
cerebrovascular disease, and
hypertension. Recent insights into the pathogenesis of
intracerebral hemorrhage have focused on underlying arterial vasculopathies that predispose to
bleeding, particularly in the elderly. The rate of major extracranial
hemorrhage on oral
anticoagulant therapy ranges from 0.4 to 2% per year. Different definitions of major
hemorrhage, INR target ranges, age distribution, burden of comorbid illness, and type of
coumarin challenge comparability of studies. Additional risk factors for major
hemorrhage include history of gastrointestinal
bleeding, concurrent use of antiplatelet or nonsteroidal anti-inflammatory drugs, genetic differences in
warfarin metabolism, INR variability, type of
coumarin, comorbid illnesses, and duration of oral
anticoagulant therapy.