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Neurocrit Care. 2016 Feb;24(1):6-46. doi: 10.1007/s12028-015-0222-x.

Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage: A Statement for Healthcare Professionals from the Neurocritical Care Society and Society of Critical Care Medicine.

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The Cerebrovascular Center, Neurological Institute, Cleveland Clinic and Case Western Reserve University, 9500 Euclid Ave. S80, Cleveland, OH, 44195, USA.
The Departments of Pharmacy and Anesthesiology & Critical Care Medicine, The Johns Hopkins Hospital and Johns Hopkins University School of Medicine, Baltimore, MD, USA.
The Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
The University of Tennessee Health Science Center, Memphis, TN, USA.
Australian Catholic University, Sydney, Australia.
Department of Pharmacy (UK Healthcare) & Department of Pharmacy Practice & Science (UK College of Pharmacy), University of Kentucky, Lexington, KY, USA.
The Departments of Medicine (Hematology) and Neurology, University of Washington School of Medicine, Seattle, WA, USA.
The Departments of Neurology, Neurosurgery, Anesthesiology & Critical Care, Perelman School of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
The Department of Laboratory Medicine and Pathology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical School, New York, NY, USA.
The Department of Neurosurgery, Westchester Medical Center, New York Medical College, Valhalla, NY, USA.
Hôpital du Sacré-Coeur and University of Montreal and Montreal Neurological Institute and McGill University, Montreal, Quebec, Canada.
Klinik für Neurologie, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany.
The Neuroscience and Neurosurgery Departments, Centra Lynchburg General Hospital, Lynchburg, VA, USA.



The use of antithrombotic agents, including anticoagulants, antiplatelet agents, and thrombolytics has increased over the last decade and is expected to continue to rise. Although antithrombotic-associated intracranial hemorrhage can be devastating, rapid reversal of coagulopathy may help limit hematoma expansion and improve outcomes.


The Neurocritical Care Society, in conjunction with the Society of Critical Care Medicine, organized an international, multi-institutional committee with expertise in neurocritical care, neurology, neurosurgery, stroke, hematology, hemato-pathology, emergency medicine, pharmacy, nursing, and guideline development to evaluate the literature and develop an evidence-based practice guideline. Formalized literature searches were conducted, and studies meeting the criteria established by the committee were evaluated.


Utilizing the GRADE methodology, the committee developed recommendations for reversal of vitamin K antagonists, direct factor Xa antagonists, direct thrombin inhibitors, unfractionated heparin, low-molecular weight heparin, heparinoids, pentasaccharides, thrombolytics, and antiplatelet agents in the setting of intracranial hemorrhage.


This guideline provides timely, evidence-based reversal strategies to assist practitioners in the care of patients with antithrombotic-associated intracranial hemorrhage.


Activated prothrombin complex concentrates; Alteplase; Anticoagulant; Antidote; Antiplatelet; Antithrombotic; Apixaban; Aspirin; Clopidogrel; Coumadin; Cryoprecipitate; DDAVP; DTI; Dabigatran; Desmopressin; Direct thrombin inhibitor; Edoxaban; FEIBA; FFP; Factor Xa inhibitor; Fondaparinux; Fresh frozen plasma; GRADE criteria; Guideline; Heparin; Heparinoid; ICH; Intracerebral hemorrhage; Intracranial hemorrhage; Intraparenchymal hemorrhage; Low-molecular weight heparin; PCC; Pentasaccharide; Plasminogen activator; Platelets; Protamine; Prothrombin complex concentrates; Recombinant factor VIIa; Reversal; Rivaroxaban; SAH; SDH; Subarachnoid hemorrhage; Subdural hematoma; TPA; Thrombolytic; VKA; Vitamin K antagonist; Warfarin; aPCC; rFVIIa; rtPA

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