Risk
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Pts with mechanical heart valves, atrial fibrillation, pulm embolism, or recent venous thrombosis.
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Oral anticoagulant therapy (warfarin, oral Xa inhibitor-rivaroxaban, apixaban, and edoxaban) and direct thrombin inhibitor (dabigatran) and use of low-molecular-weight heparin, fondaparinux may increase potential risks in elective or emergency surgery.
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Other populations include pts who receive heparin IV before vascular or cardiac surgery and pts undergoing cardiac surgery with extracorporeal circulation.
Worry About
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Excessive allogeneic transfusions, either to correct effects of anticoagulation or for risk of excessive bleeding.
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In pts with valvular heart disease, concomitant hepatic dysfunction due to HF may produce abnormal PT and/or thrombocytopenia.
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Heparin-induced thrombocytopenia can be associated with heparin therapy due to acute administration or prolonged use (∼5 d).
Overview
Heparin (Standard Unfractionated)
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For preventive therapy and acute management, cofactor antithrombin III binds to thrombin and factor X to inhibit their effects.
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Variability in response to heparin depends on:
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Prep of heparin administered.
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Individual characteristics of pts.
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Duration of therapy (due to decreased antithrombin III levels).
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Duration of action depends on dose and method of administration.
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100 U/kg: T ½ 56 min.
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IV: 60 min.
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400 U/kg: T ½ tripled.
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SQ: 3 h.
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Depolymerized in endothelial cells.
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Eliminated in urine.
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Heparin resistance (many proteins neutralize anticoagulant therapy; prolonged therapy can lower antithrombin III levels).
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Monitoring of the anticoagulant effect: PTT or ACT.
Heparin (LMWH)
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T ½ 4 to 7 h
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Higher and more predictable bioavailability: 100%
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Removed by renal filtration; accumulates with renal failure
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Not reversed with protamine; no current reversal therapy except time
Heparin Reversal Treatment
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Protamine reversal according to the ratio heparin:protamine 1:1.3 (or start with 50 to 100 mg and check the ACT)
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Monitoring: ACT in cardiac surgery
Warfarin
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Oral anticoagulant.
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Member of the coumarin family.
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Vitamin K antagonist causing inactivation of factors II, VII, IX, and X and anticoagulants C/S.
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Used for thromboembolic complication prevention.
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Peak plasma concentration reached 1-4 h after ingestion.
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T ½ : 36 to 42 h.
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INR required: 2-3.
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Stop for surgery: bridge with heparin, but new data questions this.
Warfarin Reversal Treatment
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Vitamin K: 10-20 mg PO, lower doses IM, or IV, but takes several days for normalization of INR
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Fresh frozen plasma starting with 2 U but higher doses required, Tx reactions common or circulatory overload, and lowest INR ∼1.5
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Purified protein concentrates of II, VII, IX, and X with protein C/S (KCENTRA in US); Beriplex and Octaplex outside of US
Novel Agents Approved in Other Countries Not Yet Available in the United States
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Rivaroxaban, apixaban and edoxaban are oral Xa inhibitors.
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Dabigatran is an oral thrombin inhibitor.
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These agents studied in periop DVT prophylaxis and AF treatment.
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For dabigatran reversal, idarucizumab, a monoclonal antibody Rx, at 5 g, completely reverses its effects (Praxbind).
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For Xa reversal, andexanet is under investigation, but growing data about use of PCCs in this setting.
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