REVERSAL of ORAL ANTICOAGULANTS
Mehmet Ali Karaca1
1Emergency Medicine, Hacettepe University, Turkey
Warfarin is most frequntly used (worldwide) oral anticagulant. It inhibit synthesis of vitamin K dependent factors of F II, VII, IX and X. Direct acting oral anticoagulants (DOAK or NOAC) also inhibit active F IIa and FXa.
Major complication of wafrarin treatment is bleeding. Most frequent bleedings are gastrointestinal (60%), urinary system (15%) bleeding. Most frequent lethal bleeding is intracranial bleeding. Annual rate of occurance of bleeding is 6,3% and of ten bleedings are lethal. Major hemorrage (intracranial, hospitalization rate and mortality) rate in pear year is 1,2-8.1%. The risk is higher in the first 3 months (frequently gastrointestinal and urinary).
If the INR levels increase bleeding risk is incerased. Approximately each 0.5 level increase in the level of INR results in increase of major bleeding by 1.43 times.
Guidelines advices us to reduce INR level as soon as possible to 1,5 or 2.1. In non serious bleeding target INR level is 2.1. First step warfarin should be ceased and vitamin K1 5-10 mg administered intravenously and PCC is used in dosage of 35-50 IU/kg. In serious bleeding target INR is lower than 1,5 and Vitamin K (10 mg IV) and PCC (25-50 IU/kg) should be administered.
Australian Guidelines and other guidelines (ACEP, British, ACCP and ESO) set treatment in the groups such as critical organ bleeding, significant bleeding (non life threatining) and minow bleeding. Also reversal of INR in patients without bleeding is planned according to INR levels and bleeding risk of patients.
There are many study to reveal exact dosage of PCC in bleeding. Nowadays most frequently used dosage protokol is Individualised Dosing Regimen, and the necessary dosage is calculated into account the target INR, initial INR and body weight. PCC act fast and reverse INR levels less than 15 minutes. In many studies revealed that PCC can be safely used in emergency situations (eg. emergency surgery and severe bleeding) with rapid correciton of coagulopathy with many advantages.
New Oral Anticoagulants (NOAC or DOAC) are dabigatran, rivaroxaban, apixaban and edoxaban.
Treatment strategies of bleeding related to dabidatran is supportive treatment, gastric lavage and active charcoal usage, hemodialysis and hemoperfusion and use of Idarucizumab.
Idarucizumab (Praxbind) is human derived highly selective and specific monoclonal antibody fragments (Fab). It is used for emergency surgery or urgent procedures, or in the event of life threating or uncolloed bleeding related to dabigatran usage.
In reversal of Rivaroxaban and Apixaban, supportive treatment should be administered. Hemodialysis and hemoperfusion are not effective. Andexanet alfa is newly product bind to FXa inhibitors and it is under the development.
There are limited data in reversal of NOAC by PCC and some studies support limited effect of PCC. In emergent conditions PCC and FFP should be administered in revelsal of dabigatran and rivaroxaban and apixaban. Recommended dosage of PCC in reversal of NOAC is 25-50 IU/kg. The effect of PCC decrease after 6-7 hours and it require re-dosing.