Table 2

Strategies and rationale for anticoagulation reversal in acute ICH

AnticoagulantReversal strategyRationale
Warfarin(1) Stop warfarin immediately and check the INR, but don’t wait for the result to act in life-threatening bleeds.60 61
(2) Vitamin K 10 mg intravenous infusion (slow-acting), monitor for anaphylaxis.
(3) Four-factor prothrombin complex concentrate with INR-based dosing.
(4) Repeat INR every 3–6 hours; the optimal target is uncertain, but aim for normalisation of the INR (<1.3).
Prothrombin complex concentrate is superior to fresh frozen plasma in normalising the INR for warfarin-associated ICH.62 Vitamin K administration, in addition, may help to prevent a later re-increase in INR.63
Dabigatran(1) Stop dabigatran immediately, check thrombin time, activated partial thromboplastin time.
(2) Consider oral-activated charcoal (50 g) if last intake is <4 hours and safe to administer to the patient.
(3) Idarucizumab 2×2.5 g boluses intravenously if recent ingestion or prolonged laboratory clotting times (not recommended if the thrombin time is within the normal range).
Idarucizumab, a humanised monoclonal antibody fragment, rapidly and safely reverses dabigatran anticoagulation.64 Effects on haematoma expansion are uncertain, as follow-up imaging was not mandated in the trial.
Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban and betrixaban)(1) Stop the agent immediately, check prothrombin time, anti-factor Xa activity.
(2) Consider oral-activated charcoal (50 g) if last intake is <4 hours and safe to administer to the patient.
(3) Andexanet alpha intravenous bolus and infusion, dosing dependent on the dose and last dose timing of the factor Xa inhibitor.
(4) Most centres have protocols prescribing the use of andexanet alpha; prothrombin complex concentrate is still more often used in practice.65
Andexanet alpha, a recombinant inactive factor Xa ‘decoy’, rapidly and effectively reduces anti-factor Xa activity.66 A trial in ICH is ongoing. Given that clinical and cost-effectiveness has not yet been confirmed, a recent National Institute for Health and Care Excellence (NICE) guideline consultation has not recommended its use.67
Heparin(1) Stop heparin infusion/low-molecular-weight heparin (LMWH) immediately, check activated partial thromboplastin time.
(2) Protamine sulphate slow intravenous infusion, 1 mg per 100 units of heparin, if activated partial thromboplastin time is prolonged or heparin was administered within the previous 2 hours.
(3) Max dose 50 mg, monitor for anaphylaxis.
Protamine sulphate fully reverses the effect of unfractionated heparin but only partly neutralises the effect of LMWH; the same dosing strategy can be used, but the longer half-life of LMWH may require cautious repeat infusions.68 Further evidence is needed to establish the role of andexanet alpha in the management of LMWH-associated ICH; trials are ongoing.69
  • ICH, intracerebral haemorrhage.