Complications of oral anticoagulant therapy: bleeding and nonbleeding, rates and risk factors.

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.