Reversal of Unfractionated Heparins & LMWH

Protamine Sulfate

• 1 mg of protamine sulfate neutralizes ~100 units of heparin; maximum dose is 50 mg, infuse at 5 mg/min
• Rebound heparin effect may be seen if heparin or large I.V. doses of heparin are given (i.e. in CABG)
• Anticoagulant properties at high doses

Unfractionated Heparin (Grade 1B Evidence)

May give additional protamine if warranted after at least 10 minutes.

Enoxaparin**

Dalteparin and Tinzaparin**

Half-life is longer with subcutaneous administration for all agents so may require monitoring with APTT (heparin) or anti-Xa level (LMWH) every 3 hrs with repeat protamine (0.5 mg per indicated amount of LMWH or heparin) if bleeding continues.

Anti-Xa activity is never completely neutralized (maximum ~60-75%).

* >12 hrs: Protamine unlikely to be useful.
** If bleeding continues: Repeat infusion of 0.5 mg protamine sulfate per 1 mg of enoxaparin or 100 anti-Xa units of Dalteparin or Tinzaparin may be required. Monitor APTT for heparin or anti-Xa level for LMWH every 2 to 4 hours.