Race against the clock: Overcoming challenges in the management of anticoagulant-associated intracerebral hemorrhage

Abstract

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.

Emergency management of stroke in the era of mechanical thrombectomy

“…128,129 However, because in these trials the actual blood pressure was closer to 140 mmHg, many clinicians have interpreted these studies as showing a benefit of having a lower blood pressure and recent guidelines 127 reflect a blood pressure closer to 140 mmHg systolic. Prothrombin complex concentrates, the activated prothrombin complex concentrate FEIBA (factor VIII inhibitor bypassing activity), recombinant activated factor VIIa, and vitamin K have emerged as potential therapies for bleeding related to anticoagulants 127,130 but may be harmful in those not previously on anticoagulation. Specifically, recombinant activated factor VIIa is not recommended as there is an increased thrombotic risk associated with this treatment.…”

Hemostasis in Intracranial Hemorrhage

“…The use of NOAC for systemic anticoagulation has increased dramatically due to their putative advantages versus warfarin, rapidly growing proportion of elderly Americans, and the expanding indications for NOAC medications. NOAC have a shorter half-life (5–15 h), fewer food and drug interactions, fixed dosing, no need for frequent blood monitoring, and a rapid and reliable duration to onset and offset (68). …”

Subdural Hematoma and Oral Anticoagulation: A Therapeutic Dilemma from the Neurosurgical Point of View

“…Overall, it appears that neurosurgeons tend to be more hesitant to do so than internists and cardiologists. 40,41 The decision to restart oral anticoagulation therapy should balance the risk of a second hemorrhage and the risk of a thromboembolic event. Both Broderick et al and Appelboam et al recommend distinguishing between low-risk cases (e.g., past history of deep vein thrombosis or pulmonary embolism), in which the risk of suffering a repeated hemorrhage might outweigh the benefit of repeated anticoagulation, and high-risk cases (e.g., prosthetic heart valves and chronic atrial fibrillation with prior ischemic events) in which resumption of oral anticoagulation is unavoidable.…”

“…We would like to stress the multidisciplinary approach in these patients that result in individualized recommendation for every single patient. 41 Future studies also need to investigate newer anticoagulant drugs. After reassessment of the indication for oral anticoagulation, categorizations like "absolute" or "relative" would help identify patients who would benefit from the resumption versus withdrawal.…”