Ohsu guide to reversing antithrombotic therapy

OHSU Hospital and Clinics
Department of Pharmacy Services
Pharmacy and Therapeutics Committee
October 2011
ANTICOAGULANTS: THE GUIDE TO REVERSAL
Definition of Bleeding:
Minor bleeding – Any clinically overt sign of hemorrhage (including imaging) that is associated with
a <5 g/dl decrease in the hemoglobin concentration or < 15% decrease in the hematocrit felt by the
clinician to be related to anticoagulation
Major bleeding – Intracranial hemorrhage or a ≥5 g/dl decrease in the hemoglobin concentration or
a ≥15% absolute decrease in the hematocrit resulting in hemodynamic compromise or compression
of a vital structure and felt by the clinician to be related to anticoagulation
ANTIPLATELET AGENTS
Aspirin
Minor – desmopressin 0.3 mcg/kg x 1
Major - platelet transfusion
Clopidogrel (Plavix®)
Minor – desmopressin 0.3 mcg/kg x 1
Major - platelet transfusion – consider two units if life or brain threatening bleeding
Prasugrel (Effient®)
Minor – desmopressin 0.3 mcg/kg x 1
Major - platelet transfusion – consider two units if life or brain threatening bleeding
Ticagrelor (Brilinta®)
Minor – desmopressin 0.3 mcg/kg x 1
Major - platelet transfusion – consider two units if life or brain threatening bleeding
Sustained Release Aspirin/Dipyridamole (Aggrenox®)
Minor – desmopressin 0.3 mcg/kg x 1
Major - platelet transfusion
Abciximab (Reopro®)
Major - platelet transfusion
Eptifibatide (Integrilin®)
Minor – desmopressin 0.3 mcg/kg x 1
Major Bleeding Reversal: platelet transfusions plus infusion of 10 units of cryoprecipitate
Tirofiban (Aggrastat®)
Minor – desmopressin 0.3 mcg/kg x 1
Major bleeding Reversal: platelet transfusions plus infusion of 10 units of cryoprecipitate
HEPARIN AND HEPARIN LIKE AGENTS
Standard Heparin
Time since last heparin dose
Dose of Protamine
Infusion rate should not exceed 5 mg/min. Maximum dose is 50 mg per dose Low Molecular Weight Heparin
Reversal of Bleeding: Protamine (works just as well with LMWH as heparin) - if with-in 4 hours of dose:
1 mg of protamine for each 1 mg of enoxaparin or 100 units of daltaparin and tinzaparin. Repeat one-
half dose of protamine in 4 hours. If 4-8 hours after dose: give 0.5 mg for each 1 mg of enoxaparin
or 100 units of daltaparin and tinzaparin.
Fondaparinux (Arixtra®)
Major Bleeding Reversal - Protamine ineffective - rVIIa (90 mcg/kg) may be of use
Dabigatran (Pradaxa®)
Reverse if patient shows signs of bleeding and had an elevated aPTT > 40 seconds
1. Profilnine (Factor IX complex) 4000 units (50 units/kg for patients under 80 kg) plus 1 mg of Rivaroxaban (Xarelto®)
Reverse if patient shows signs of bleeding and has an INR > 1.5
1. Profilnine (Factor IX complex) 4000 units (50 units/kg for patients under 80 kg) plus 1 mg of THROMBOLYTIC THERAPY
Reversal: Immediate infusions of equivalent of 6-8 units of platelets (or one platelet pheresis product), 2 units of plasma, and 10 units of cryoprecipitate. No value in infusing anti-fibrinolytic agents WARFARIN
Not Bleeding: Goal is INR in 2-3 range
Should see INR back in therapeutic range in 24-48 hours Bleeding: Goal is INR under 2
FFP: Fresh Frozen PlasmaLife or Brain Threatening: Profilnine 4000 units + 1 mg rVIIa References:
1. Beshay JE, Morgan H, Madden C, Yu W, Sarode R. Emergency reversal of anticoagulation and antiplatelet
therapies in neurosurgical patients. J Neurosurg. 2010;112(2):307-18.
2. Bijsterveld NR, Moons AH, Boekholdt SM, Van Aken BE, Fennema H, Peters RJ, Meijers JC, Buller HR, Levi M.
Ability of recombinant factor VIIa to reverse the anticoagulant effect of the pentasaccharide fondaparinux in
healthy volunteers. Circulation. 2002;106:2550-2554.
3. Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and
dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in
healthy subjects. Circulation. 2011;124(14):1573-9
4. Elg M, Carlsson S, Gustafsson D. Effects of agents, used to treat bleeding disorders, on bleeding time
prolonged by a very high dose of a direct thrombin inhibitor in anesthesized rats and rabbits. Thrombosis
Research. 2001;101:159-170.
5. Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on
Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:188S-203S.
6. Li YF, Spencer FA, Becker RC. Comparative efficacy of fibrinogen and platelet supplementation on the in
vitro reversibility of competitive glycoprotein IIb/IIIa receptor-directed platelet inhibition. Am Heart J.
2002;143:725-732.
7. Prüller F, Drexler C, Archan S, Macher S, Raggam RB, Mahla E. Low platelet reactivity is recovered by
transfusion of stored platelets: a healthy volunteer in vivo study. J Thromb Haemost. 2011;9(8):1670-3.
8. Reiter RA, Mayr F, Blazicek H, Galehr E, Jilma-Stohlawetz P, Domanovits H, Jilma B. Desmopressin
antagonizes the in vitro platelet dysfunction induced by GPIIb/IIIa inhibitors and aspirin. Blood.
2003;102:4594-4599.
9. Sane DC, Califf RM, Topol EJ, Stump DC, Mark DB, Greenburg CS. Bleeding during Thrombolytic Therapy for
Acute Myocardial Infeaction: Mechanism and Management. Ann Intern Med. 1989;111:1010-1022.
10. Van Ryn J, Stangier J, Haertter S, Liesenfeld KH, Wienen W, Feuring M, Clemens A. Dabigatran etexilate--a
novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of
anticoagulant activity. Thromb Haemost. 2010;103(6):1116-27.
11. Van Ryn-McKenna J, Cai L, Ofosu FA, Hirsh J, Buchanan MR. Neutralization of enoxaparine-induced
bleeding by protamine sulfate. Thromb Haemost. 1990;63:271-274.
12. Zhou W, Schwarting S, Illanes S, Liesz A, Middelhoff M, Zorn M, Bendszus M, Heiland S, van Ryn J, Veltkamp
R. Hemostatic Therapy in Experimental Intracerebral Hemorrhage Associated With the Direct Thrombin
Inhibitor Dabigatran. Stroke. 2011.
Created by Tom Deloughery, MD FACPReviewed by Drug Information ServiceDate: Oct 25 2011

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