Intracerebral haemorrhage associated with antithrombotic treatment: translational insights from experimental studies

Little is known about the pathophysiology of intracerebral haemorrhage that occurs during anticoagulant treatment. In observational studies, investigators have reported larger haematoma volumes and worse functional outcome in these patients than in those with intracerebral haemorrhage and a normal coagulation status. The need to prevent extensive haematoma enlargement by rapid reversal of the anticoagulation seems intuitive, although no evidence is available from randomised clinical trials. New oral anticoagulants, such as the direct thrombin inhibitor dabigatran and the factor Xa inhibitor rivaroxaban, have been approved recently; however, intracerebral haemorrhage during dabigatran or rivaroxaban anticoagulation has not been characterised, and whether anticoagulation reversal can be beneficial in this scenario is unknown. In a translational approach, new experimental models have been developed to study anticoagulation-associated intracerebral haemorrhage in more detail and to test treatment strategies. Vitamin k antagonists enlarge haematoma volumes and worsen functional outcome in animal models. Rapid reversal of anticoagulation in the experimental setting prevents prolonged haematoma expansion and improves outcome. The new oral anticoagulants increase intracerbral haemorrhage volumes less than does warfarin. Haemostatic approaches that have been used for vitamin k-associated intracerebral haemorrhage also seem to be effective in intracerebral haemorrhage associated with the new anticoagulants. These experimental studies are valuable for filling gaps in knowledge, but the results need careful translation into routine clinical practice.