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

Overview

Journal Neurocrit Care

Specialty Critical Care

Date 2015 Dec 31

PMID 26714677

Citations 186

Authors

Jennifer A Frontera

John J Lewin 3rd

Alejandro A Rabinstein

Imo P Aisiku

Anne W Alexandrov

Aaron M Cook

Gregory J Del Zoppo

Monisha A Kumar

Ellinor I B Peerschke

Michael F Stiefel

Jeanne S Teitelbaum

Katja E Wartenberg

Cindy L Zerfoss

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Methods: 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.

Results: 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.

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

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References

Adkins J, HARDY J . Sodium heparin neutralization and the anticoagulant effects of protamine sulfate. Arch Surg. 1967; 94(2):175-7. DOI: 10.1001/archsurg.1967.01330080013004. View

Cannegieter S, Rosendaal F, Briet E . Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation. 1994; 89(2):635-41. DOI: 10.1161/01.cir.89.2.635. View

Guyatt G, Akl E, Crowther M, Gutterman D, Schuunemann H . Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):7S-47S. PMC: 3278060. DOI: 10.1378/chest.1412S3. View

Zhou W, Schwarting S, Illanes S, Liesz A, Middelhoff M, Zorn M . Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran. Stroke. 2011; 42(12):3594-9. DOI: 10.1161/STROKEAHA.111.624650. View

Lewis B, Wallis D, Leya F, Hursting M, Kelton J . Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch Intern Med. 2003; 163(15):1849-56. DOI: 10.1001/archinte.163.15.1849. View

Komori M, Yasaka M, Kokuba K, Matsuoka H, Fujimoto S, Yoshida M . Intracranial hemorrhage during dabigatran treatment. Circ J. 2014; 78(6):1335-41. DOI: 10.1253/circj.cj-13-1534. View

Morgenstern L, Hemphill 3rd J, Anderson C, Becker K, Broderick J, Connolly Jr E . Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2010; 41(9):2108-29. PMC: 4462131. DOI: 10.1161/STR.0b013e3181ec611b. View

Chapman S, Irwin E, Beal A, Kulinski N, Hutson K, Thorson M . Prothrombin complex concentrate versus standard therapies for INR reversal in trauma patients receiving warfarin. Ann Pharmacother. 2011; 45(7-8):869-75. DOI: 10.1345/aph.1P605. View

Levy J, Cormack J, Morales A . Heparin neutralization by recombinant platelet factor 4 and protamine. Anesth Analg. 1995; 81(1):35-7. DOI: 10.1097/00000539-199507000-00007. View

10.

Firozvi K, Deveras R, Kessler C . Reversal of low-molecular-weight heparin-induced bleeding in patients with pre-existing hypercoagulable states with human recombinant activated factor VII concentrate. Am J Hematol. 2006; 81(8):582-9. DOI: 10.1002/ajh.20652. View

11.

Sherman D, Albers G, Bladin C, Fieschi C, Gabbai A, Kase C . The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL Study): an open-label randomised comparison. Lancet. 2007; 369(9570):1347-1355. DOI: 10.1016/S0140-6736(07)60633-3. View

12.

Greinacher A, Thiele T, Selleng K . Reversal of anticoagulants: an overview of current developments. Thromb Haemost. 2015; 113(5):931-42. DOI: 10.1160/TH14-11-0982. View

13.

Grottke O, van Ryn J, Spronk H, Rossaint R . Prothrombin complex concentrates and a specific antidote to dabigatran are effective ex-vivo in reversing the effects of dabigatran in an anticoagulation/liver trauma experimental model. Crit Care. 2014; 18(1):R27. PMC: 4059479. DOI: 10.1186/cc13717. View

14.

Egerton W, Robinson C . The anti-heparin, anticoagulant and hypotensive properties of hexadimethrine and protamine. Lancet. 1961; 2(7203):635-7. DOI: 10.1016/s0140-6736(61)90311-7. View

15.

Reiter R, Mayr F, Blazicek H, Galehr E, Jilma-Stohlawetz P, Domanovits H . Desmopressin antagonizes the in vitro platelet dysfunction induced by GPIIb/IIIa inhibitors and aspirin. Blood. 2003; 102(13):4594-9. DOI: 10.1182/blood-2002-11-3566. View

16.

Sinzinger H, Fitscha P, Peskar B . Platelet half-life, plasma thromboxane B2 and circulating endothelial-cells in peripheral vascular disease. Angiology. 1986; 37(2):112-8. DOI: 10.1177/000331978603700207. View

17.

Dowlatshahi D, Butcher K, Asdaghi N, Nahirniak S, Bernbaum M, Giulivi A . Poor prognosis in warfarin-associated intracranial hemorrhage despite anticoagulation reversal. Stroke. 2012; 43(7):1812-7. DOI: 10.1161/STROKEAHA.112.652065. View

18.

Cai L, Ofosu F, Hirsh J, Buchanan M . Neutralization of enoxaparine-induced bleeding by protamine sulfate. Thromb Haemost. 1990; 63(2):271-4. View

19.

Cohen A, Davidson B, Gallus A, Lassen M, Prins M, Tomkowski W . Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ. 2006; 332(7537):325-9. PMC: 1363908. DOI: 10.1136/bmj.38733.466748.7C. View

20.

Holst J, Lindblad B, Bergqvist D, Garre K, Nielsen H, Hedner U . Protamine neutralization of intravenous and subcutaneous low-molecular-weight heparin (tinzaparin, Logiparin). An experimental investigation in healthy volunteers. Blood Coagul Fibrinolysis. 1994; 5(5):795-803. DOI: 10.1097/00001721-199410000-00018. View