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Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage: Executive Summary. A Statement for Healthcare Professionals from the Neurocritical Care Society and the Society of Critical Care Medicine
Frontera JA, Lewin JJ, Rabinstein AA, et al. Crit Care Med 2016; 44: 2251-2257
Study Question: What is the most appropriate reversal strategy for patients with intracranial hemorrhage (ICH) exposed to antithrombotics?
Study Description: A 13-member international, multi-disciplinary committee evaluated clinical trials, meta-analyses, review articles, and practice guidelines published through November 2015.
Results: 174 articles were included for guideline production. For the reversal of vitamin K antagonists following ICH when INR > 1.3, both vitamin K and three-factor or four-factor prothrombin complex concentrates (PCCs) received strong recommendations.
For dabigatran reversal, idarucizumab was strongly recommended if dabigatran was administered within 3-5 half-lives or for renal insufficiency resulting in longer drug exposure. The use of activated PCC (aPCC) or four-factor PCC was recommended for direct-thrombin inhibitors other than dabigatran or if idarucizumab is unavailable.
Intravenous (IV) protamine was strongly recommended for heparin and low-molecular weight heparin (LMWH) reversal, with dosing based on antithrombotic dose within previous 2-3 hours or 3-6 half-lives, respectively. aPCC was a specific, yet conditional, recommendation for reversal of pentasaccharides.
No strong evidence was available for the reversal of direct factor Xa inhibitors, but activated charcoal within 2 hours (only if low risk of aspiration) and four-factor PCC or aPCC within 3-5 half-lives were recommended. Furthermore, no strong recommendations were made for reversal of thrombolytics, but cryoprecipitate was suggested.
Guidelines for antiplatelet reversal also failed to produce strong supporting evidence; however, the authors did recommend platelet function testing prior to transfusion, and only for aspirin or adenosine diphosphate (e.g. P2Y12) inhibitors in the setting of neurosurgical procedures. Transfusion was not recommended for non-steroidal anti-inflammatories and glycoprotein IIb/IIIa inhibitors.
The use of rFVIIa was recommended against for most agents, except for danaparoid, pentasaccharides (if aPCC not available), and LMWH (if protamine contraindicated).
Conclusion(s): This guideline was an evidence-based summary which addressed the reversal of a wide array of antithrombotics in the setting of ICH.
Perspective: Caution should be made in interpretation of this article, specifically in pediatrics, or complex populations, including inherited hemophilia and liver/renal disease. The authors state that evidence is partially based on indirect outcomes; therefore, clinical experience and institutionally available resources should be taken into consideration.