Anticoagulation reversal for ICH

Warfarin reversal:


Dabigatran reversal:

Normal aPTT does not rule out clinically relevant effects of dabigatran. Thrombin time (TT) is highly sensitive to dabigatran. A normal TT rules out clinically important drug levels, but a prolonged TT does not necessarily mean that clinically important drug levels are present. TT is routinely available weekdays from 8am to 4:40 pm.

*****  Praxbind 5 g IV is new standard reversal strategy.  Discuss with heme whether repeat doses might be needed in specific case.

Rivaroxaban/Apixaban reversal:

Laboratory testing to demonstrate residual rivaroxaban/apixaban effect is problematic. The presence of severe bleeding, rather than laboratory results, should be the primary determinant of therapeutic intervention.  A prolonged PT/INR might indicate residual rivaroxaban effect , but a normal PT/INR does not rule out clinically relevant effects of rivaroxaban.   A normal anti-Xa assay excludes the presence of significant rivaroxaban levels. An abnormal anti-Xa assay might indicate residual rivaroxaban effects but this should not be used as a quantitative assessment of anticoagulant activity.  It is unknown whether this applies to apixaban as well.

***** Prothrombin complex concentrate – Kcentra- 50 units/kg x 1 is the preferred first reversal agent and does not require Hematology approval in severe or life-threatening bleeding, or for emergent or urgent procedures.  Activated PCC (50-100 units/kg x 1), rFVIIa (20-40 mcg/kg), or subsequent doses of PCC should be considered ONLY if bleeding persists after PCC AND with Hematology approval

Intravenous heparin reversal:

Since blood heparin concentrations decrease rapidly after administration, adjust the protamine dosage depending upon the duration of time since heparin administration as follows:
Time Elapsed                      Protamine dose (mg) to Neutralize 100 units heparin
Immediate                                                    1-1.5
30-60 min                                                  0.5-0.75
>2 hours                                                    0.25-0.375


Enoxaparin reversal:

**** Protamine 1 mg for each mg of enoxaparin (1 mg of e noxaparin is equal to 100 international units of anti-Xa activity). Max rate: 50 mg over 10 minutes.

If aPTT prolonged 4 hours after first dose, consider additional dose of 0.5 mg for each mg of enoxaparin.
Avoid overdosage with protamine as excessive protamine doses can potentiate bleeding.
Due to fatal anaphylactoid-like reactions associated with protamine, it should be given only when resuscitation techniques and treatment of anaphylactic shock are readily available.
Diphenhydramine dosing for allergic reactions–I.M., I.V.: 10-50 mg per dose; single doses up to 100 mg may be used if needed; not to exceed 400 mg/day


NOTE:  Anti-factor Xa activity never completely neutralized (max ~60%-75%).