European Stroke Organisation Guideline on Reversal of Oral Anticoagulants in Acute Intracerebral Haemorrhage

Abstract

The aim of the present European Stroke Organisation guideline document is to provide clinically useful evidence-based recommendation on reversal of anticoagulant activity VKA (warfarin, phenprocoumon and acenocoumarol), direct factor II (thrombin) inhibitors (dabigatran etexilat) and factor-Xa-inhibitors (apixaban, edoxaban and rivaroxaban) in patients with acute intracerebral haemorrhage. The guideline was prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined use of oral anticoagulation pragmatically: oral anticoagulation use is assumed by positive medical history unless relevant anticoagulant activity is regarded unlikely by medical history or has been ruled out by laboratory testing. Overall, we strongly recommend using prothrombin complex over no treatment and fresh-frozen plasma in patients on VKA plus vitamin K. We further strongly recommend using idarucizumab in patients on dabigatran and make a recommendation for andexanet alfa in patients on rivaroxaban and apixaban over no treatment. We make a weak recommendation on using high-dose prothrombin complex concentrate (50 IU/kg) for all patients taking edoxaban and for patients on rivaroxaban or apixaban in case andexanet alfa is not available. We recommend against using tranexamic acid and rFVIIa, outside of trials. The presented treatment recommendations aim to normalise coagulation, there is no or only indirect data on effects on functional outcome or mortality, and only little data from randomised controlled trials.

Propensity Score Adjusted Comparison of Three-Factor versus Four-Factor Prothrombin Complex Concentrate for Emergent Warfarin Reversal: A Retrospective Cohort Study

“…There is a need for better understanding of the similarities and differences in these agents in terms of anticoagulation reversal response and patient e cacy and safety outcomes. Recent guidelines recommend the use of a PCC4 product, plus vitamin K, for urgent reversal of the effects of warfarin with INR as a measure of effective reversal (1,4,(8)(9)(10)(11)(12)(13). The recommendation for a PCC4 product over PCC3 is based on the theoretical advantage of the additional factor VII component and randomized, controlled studies that compared PCC4 to FFP (15,16), and was not based on any prospective data comparing EWR with PCC3 vs. PCC4 products.…”

“…Several recent guidelines recommend PCC4 (along with vitamin K), as a rst line agent for emergent warfarin reversal (EWR). Plasma is recommended as an alternative if PCC4 is not available (1,4,(8)(9)(10)(11)(12)(13). Prior to 2013, only PCC3 products were available in the United States (US).…”

From Rat Poison to Medicine: Medical Applications of Coumarin Derivatives

“…When acute termination of anticoagulation is necessary with unwanted bleeding like in menstruating women and after blunt and sharp trauma leading to hemorrhage, it could take days before the process of coagulation completely restores after quitting oral administration [27,30] due to the depletion of coagulant factors in liver and blood. In these cases, intravenous administration of prothrombin complex, fresh frozen plasma with coagulation factors, and high doses of vitamin K may be helpful [45].…”

Reply to “Key Points to Consider When Evaluating Andexxa for Formulary Addition”

“…Many guidelines were written before the availability of andexanet alfa and final ANNEXA-4 study results, and are currently under revision. More recent guidelines are placing andexanet alfa as a first-line agent in front of PCC [3][4][5][6][7][8].…”