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.

*****  Idarucizumab2 (Praxbind®) 5 grams IV (two infusions of 2.5 grams IV given within 15 minutes of each other) is the preferred first reversal agent. 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.

***** Andexanet Alfa with dosing based on type and dose of DOAC is the preferred reversal agent.  If last dose was apixaban 5 mg or less or rivaroxaban 10 mg or les, give andexanet 400 mg IV bolus administered at a rate of 30 mg/minute, followed 2 minutes later by 4 mg/minute IV infusion for up to 120 minutes.  If last dose was apixaban more than 5 mg or rivaroxaban more than 10 mg, give 800 mg IV bolus administered at a rate of 30 mg/minute, followed 2 minutes later by 8 mg/minute IV infusion for up to 120 minutes.

Prothrombin complex concentrate – Kcentra- 50 units/kg x 1 may be considered if a lower risk of hemorrhagic expansion is anticipated; it is much less expensive.  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%).