Patients receiving anticoagulation therapy who present with any type of intracranial hemorrhage--including subdural hematoma, epidural hematoma, subarachnoid hemorrhage, and intracerebral hemorrhage (ICH)--require urgent correction of their coagulopathy to prevent hemorrhage expansion, limit tissue damage, and facilitate surgical intervention as necessary. The focus of this review is acute ICH, but the principles of management for anticoagulation-associated ICH (AAICH) apply to patients with all types of intracranial hemorrhage, whether acute or chronic. A number of therapies--including fresh frozen plasma (FFP), intravenous vitamin K, activated and inactivated prothrombin complex concentrates (PCCs), and recombinant activated factor VII (rFVIIa)--have been used alone or in combination to treat AAICH to reverse anticoagulation, help achieve hemodynamic stability, limit hematoma expansion, and prepare the patient for possible surgical intervention. However, there is a paucity of high-quality data to direct such therapy. The use of 3-factor PCC (activated and inactivated) and rFVIIa to treat AAICH constitutes off-label use of these therapies in the United States. However, in April 2013, the US Food and Drug Administration (FDA) approved Kcentra (a 4-factor PCC) for the urgent reversal of vitamin K antagonist (VKA) anticoagulation in adults with acute major bleeding. Plasma is the only other product approved for this use in the United States. (1) Inconsistent recommendations, significant barriers (e.g., clinician-, therapy-, or logistics-based barriers), and a lack of approved treatment pathways in some institutions can be potential impediments to timely and evidence-based management of AAICH with available therapies. Patient assessment, therapy selection, whether to use a reversal or factor repletion agent alone or in combination with other agents, determination of site-of-care management, eligibility for neurosurgery, and potential hematoma evacuation are the responsibilities of the neurosurgeon, but ultimate success requires a multidisciplinary approach with consultation from the emergency department (ED) physician, pharmacist, hematologist, intensivist, neurologist, and, in some cases, the trauma surgeon.
Keywords: 3PCC = three-factor prothrombin complex concentrate; 4PCC = four-factor prothrombin complex concentrate; AAICH = anticoagulation-associated intracerebral hemorrhage; AF = atrial fibrillation; AHA = American Heart Association; ASA = American Stroke Association; BP = blood pressure; BT = bleeding time; CI = confidence index; CT = computed tomography; CYP = cytochrome P450; DVT = deep vein thrombosis; ECT = ecarin clotting time; ED = emergency department; FFP = fresh frozen plasma; GCS = Glasgow Coma Scale; HR = heart rate; ICES = intraoperative computed tomography-guided endoscopic surgery procedure; ICH = intracerebral hemorrhage; INR = international normalized ratio; IV = intravenous; IVH = intraventricular hemmorhage; MISTIE = Minimally Invasive Surgery plus recombinant Tissue plasminogen activator for ICH Evaluation procedure; NOAC = novel oral anticoagulant; OAC = oral anticoagulant; PCC = prothrombin complex concentrate; PE = pulmonary embolism; PHE = perihematomal edema; PT = prothrombin time; PTT = partial thromboplastin time; RR = respiratory rate; TT = thrombin time; VKA = vitamin K antigen; aPTT = activated partial thromboblastin time; bpm = beats per minute; rFVIIa = recombinant factor VII; rt-PA = recombinant tissue plasminogen activator.