What is the reversal agent for heparin (Heparin)

From the Guidelines

Protamine sulfate is the primary reversal agent for heparin, and it should be administered intravenously at a dose of 1 mg per 100 units of heparin, with a maximum single dose of 50 mg, as recommended by the most recent guidelines 1. When immediate reversal of heparin's anticoagulant effects is needed, protamine should be used. The dose should be adjusted based on the time elapsed since heparin administration, with less protamine needed if more time has passed.

• Protamine works by binding to heparin molecules to form a stable complex that lacks anticoagulant activity.
• The reversal effect occurs rapidly, usually within minutes of administration.
• Clinicians should monitor patients closely during administration as protamine can cause hypotension, bradycardia, and allergic reactions, with higher risk in patients with fish allergies, prior protamine exposure, or those who have received protamine-containing insulins.
• After administration, coagulation studies should be performed to confirm adequate reversal. For low molecular weight heparins, protamine is partially effective, neutralizing about 60-80% of the anticoagulant activity, and may require adjusted dosing strategies 1. Some key points to consider when using protamine include:
• The dose of protamine should not exceed 50 mg/10 min due to the risk of hypotension and bronchoconstriction 1.
• Repeated smaller doses are preferable to minimize the risk of adverse effects.
• Protamine only partially affects anti–factor Xa levels, which can be used to assess the amount of anticoagulant present but do not predict the effect of protamine 1.

From the FDA Drug Label

Neutralization of Heparin Effect When clinical circumstances (bleeding) require reversal of the heparin effect, protamine sulfate (1% solution) by slow infusion will neutralize heparin sodium. No more than 50 mg should be administered, very slowly, in any 10-minute period Each mg of protamine sulfate neutralizes approximately 100 USP heparin units.

The reversal agent for heparin is protamine sulfate. It should be administered by slow infusion, with no more than 50 mg given in any 10-minute period. Each mg of protamine sulfate neutralizes approximately 100 USP heparin units 2.

From the Research

Reversal Agents for Heparin

• Protamine sulfate is a specific antidote for unfractionated heparin (UFH) and can reverse its anticoagulant effect completely 3, 4, 5.
• Protamine sulfate can also reverse the effect of low-molecular-weight heparin (LMWH) partially, but it has negligible effects on other anticoagulants like danaparoid and fondaparinux 3.
• The use of protamine sulfate can be associated with life-threatening side effects such as systemic hypotension, catastrophic pulmonary vasoconstriction, or allergic reactions 4.
• New alternatives to protamine sulfate, such as UHRA, LMWP, and Dex40-GTMAC3, are in the preclinical stage, while andexanet alfa and PER977 are in advanced clinical phases 4.
• Fresh frozen plasma can also be used to reverse heparin resistance during cardiopulmonary bypass, and it can lessen total heparin requirements during the procedure 6.

Management of Bleeding in Patients on Heparin

• Bleeding patients on heparin should be risk-stratified based on hemodynamic instability, source of bleeding, and degree of blood loss 5.
• Minor bleeding may be managed with discontinuation of anticoagulant, while major bleeding may require transfusion of blood products and use of specific antidotes like protamine sulfate 5.
• The residual effects of heparin can be monitored with distinct coagulation assays, and protamine sulfate can be used to reverse its effect completely 5.