Restarting and timing of oral anticoagulation after traumatic intracranial hemorrhage: a review and summary of ongoing and planned prospective randomized clinical trials

Anticoagulant-associated traumatic intracranial hemorrhage (tICrH) is a devastating injury with high morbidity and mortality. For survivors, treating clinicians face the dilemma of restarting oral anticoagulation with scarce evidence to guide them. Thromboembolic risk is high from the bleeding event, patients’ high baseline risks, that is, the pre-existing indication for anticoagulation, and the risk of immobility after the bleeding episode. This must be balanced with potentially devastating hematoma expansion or new hemorrhagic lesions. Retrospective evidence and expert opinion support restarting oral anticoagulants in most patients with tICrH, but timing is uncertain. Researchers have failed to make clear distinctions between tICrH and spontaneous intracranial hemorrhage (sICrH), which have differing natural histories. While both appear to benefit from restarting, sICrH has a higher rebleeding risk and similar or lower thrombotic risk. Clinical equipoise on restarting is also divergent. In sICrH, equipoise is centered on whether to restart. In tICrH, it is centered on when. Several prospective randomized clinical trials are ongoing or about to start to examine the risk–benefit of restarting. Most of them are restricted to patients with sICrH, with antiplatelet control groups. Most are also restricted to direct oral anticoagulants (DOACs), as they are associated with a lower overall risk of ICrH. There is some overlap with tICrH via subdural hematoma, and one trial is specific to restart timing with DOACs in only traumatic cases. This is a narrative review of the current evidence for restarting anticoagulation and restart timing after tICrH along with a summary of the ongoing and planned clinical trials.