. 2019 Aug 6;20(5):770–783. doi: 10.5811/westjem.2018.5.38235

Table 4.

Dosage of reversal agents for heparin, low-molecular-weight heparins, and synthetic pentasaccharides—fondaparinux (Arixtra).

Agent	Dose	Additional Information
Protamine for Heparin	Time elapsed from last heparin dose: Dose of protamine (mg) to neutralize 100 units of heparin Immediate: 1–1.5 mg/100 units heparin 30–60 min: 0.5–0.75 mg/100 units heparin >2 h: 0.25–0.375/100 Units Heparin	Doses should not exceed 50 mg at a time.
Protamine for LMWH	Dalteparin (Fragmin): 1 mg protamine neutralizes 100 units dalteparin If bleeding continues or PTT remains prolonged 2–4 hours after protamine, may give a second protamine dose of 0.5 mg per 100 units dalteparin. Enoxaparin (Lovenox): if < 8 hours after last dose enoxaparin, give 1 mg protamine per 1 mg enoxaparin; If 8–12 hours after last dose enoxaparin, give 0.5 mg protamine per 1 mg enoxaparin. If >12 hours after last dose of enoxaparin (when enoxaparin administered q12h), protamine not required. If bleeding continues or PTT remains prolonged 2–4 hours after protamine, may give a second protamine dose of 0.5 mg per 1 mg enoxaparin.	Protamine may have some effect on LMWH. Only 60–75% of the anti Xa activity of LMWH is neutralized by protamine. Effectiveness depends on which LMWH is used. There is a real concern when using protamine with LMWH: Protamine when given by itself has anticoagulant effects. If there is reversal of the non-Xa activity and only partial (but not enough) reversal of the Xa activity, the net vector will point to anticoagulation. DO NOT EXCEED 50 mg per dose. Protamine only partially neutralizes anti-factor Xa activity (~60%). Fondaparinux: Has only anti-Xa activity and protamine will have no significant effect.
Reversal of Fondaparinux	Recombinant activated factor VII (NovoSeven): 90 mcg/kg IV Activated prothrombin complex concentrate (aPCC) FEIBA 50 U/kg IV	Very limited data to recommend these agents to reverse fondaparinux.

Agent

Dose

Additional Information

Protamine for Heparin

Time elapsed from last heparin dose:
Dose of protamine (mg) to neutralize 100 units of heparin
Immediate: 1–1.5 mg/100 units heparin
30–60 min: 0.5–0.75 mg/100 units heparin >2 h: 0.25–0.375/100 Units Heparin

Doses should not exceed 50 mg at a time.

Protamine for LMWH

Dalteparin (Fragmin): 1 mg protamine neutralizes 100 units dalteparin

If bleeding continues or PTT remains prolonged 2–4 hours after protamine, may give a second protamine dose of 0.5 mg per 100 units dalteparin.

Enoxaparin (Lovenox): if < 8 hours after last dose enoxaparin, give 1 mg protamine per 1 mg enoxaparin;

If 8–12 hours after last dose enoxaparin, give 0.5 mg protamine per 1 mg enoxaparin.
If >12 hours after last dose of enoxaparin (when enoxaparin administered q12h), protamine not required.
If bleeding continues or PTT remains prolonged 2–4 hours after protamine, may give a second protamine dose of 0.5 mg per 1 mg enoxaparin.

Protamine may have some effect on LMWH. Only 60–75% of the anti Xa activity of LMWH is neutralized by protamine. Effectiveness depends on which LMWH is used. There is a real concern when using protamine with LMWH: Protamine when given by itself has anticoagulant effects. If there is reversal of the non-Xa activity and only partial (but not enough) reversal of the Xa activity, the net vector will point to anticoagulation. DO NOT EXCEED 50 mg per dose.
Protamine only partially neutralizes anti-factor Xa activity (~60%).
Fondaparinux: Has only anti-Xa activity and protamine will have no significant effect.

Reversal of Fondaparinux

Recombinant activated factor VII (NovoSeven): 90 mcg/kg IV
Activated prothrombin complex concentrate (aPCC) FEIBA 50 U/kg IV

Very limited data to recommend these agents to reverse fondaparinux.

mg, milligram; IV, intravenous; LMWH, low-molecular-weight heparin; PTT, partial thromboplastin time; q12h, every 12 hours; kg, kilogram; FEIBA, factor VIII inhibitor bypassing activity.