Transfusion medicine handbook

6. Special Circumstances

6.10 Oral Anticoagulant Induced Bleeding Or Overdose

Warfarin

Withholding warfarin along with the judicious use of oral vitamin K₁ are the management options of choice unless rapid reversal of anticoagulation is required. Although intravenous administration of vitamin K₁ produces a more rapid response (onset within 6 - 8 hours), at 24 hours both routes achieve a similar correction of INR. The intravenous route may rarely be associated with anaphylaxis. The full effect of vitamin K₁ in reducing the INR takes up to 24 hours even when given in large doses. For immediate reversal of clinically significant bleeding, treatment with human prothrombin complex concentrate (PCC)  covers the period until vitamin K₁ achieves full effect. Subsequent doses of vitamin K₁ may be necessary for maintaining correction of the INR achieved by coagulation factor replacement. If no PCC is available, FFP should be transfused, though this is less effective and carries a significant risk of Transfusion Associated Circulatory Overload at the doses required to reverse warfarin. The FFP dose for an adult in this setting is 15 mL/kg.

ASTH has guidance on warfarin reversal [6]. A summary is shown in Table 6.7.

Table 6.7: Managing Overdose or Bleeding in Patients on Warfarin Therapy

The NZBS Reversing Warfarin app developed by Health Obs Ltd, available for android and iPhone, also provides guidance for managing patients with bleeding.

Direct Oral Anticoagulants (DOAC)

There is limited clinical data on reversal of the factor Xa inhibitors rivaroxaban and apixaban. As there is no specific reversal agent available, the mainstay of current management for drug-related bleeding is withholding DOAC together with best supportive care for local control of bleeding and maintenance of haemodynamic stability. The anticoagulant effect will not be reversed by the administration of vitamin K or infusion of plasma.

Idarucizumab, a specific intravenous reversal agent for dabigatran, is available. The antibody fragment completely reverses within minutes the anticoagulant effect of dabigatran.

Guidance for the management of bleeding with DOACs has been produced by ASTH [7] and PHARMAC [8]. A joint publication from the NZ government, PHARMAC and bpac provides useful advice for dabigatran and rivaroxaban bleeding [10]. The recommendations may change as new evidence becomes available. Additionally, the Rivaroxaban app and the Dabigatran app developed by Health Obs Ltd, available for Android and iPhone, provide guidance for managing patients with bleeding.