What causes intracerebral hemorrhage during warfarin therapy?

It is a cruel irony that the use of warfarin, given to prevent ischemic stroke, increases the risk of severe hemorrhagic stroke as its most devastating complication. Conventional intensities of anticoagulation increase the risk of intracerebral hemorrhage 5 to 10 times, by absolute rates of 1% per year or more for many stroke-prone patients. The increased intracerebral bleeding associated with warfarin therapy offsets its benefits in certain patient populations. Although warfarin and related oral vitamin K antagonists have been used for stroke prevention for 50 years, more cases of anticoagulant-associated intracerebral bleeding are now reported—up to one per month at some tertiary referral hospitals,1 most occurring when the international normalized ratio (INR) is within the therapeutic range.1,2⇓ Recent use of lower intensities of anticoagulation and monitoring by INR and anticoagulation clinics makes anticoagulation safer, but these advantages are offset by wider use of anticoagulation in the elderly population, who are at increased risk for serious bleeding. The risk/benefit ratio of anticoagulant therapy for stroke prevention often hinges on differences in intracerebral hemorrhage rates of 1 to …