Reversal of Oral Anticoagulants for Intracerebral Hemorrhage Patients: Best Strategies

Abstract

In patients with acute intracerebral hemorrhage (ICH), one of the major concerns is ongoing bleeding or ICH expansion. Anticoagulated patients are at higher risk of ongoing expansion and worse outcome. It may be that rapid anticoagulation reversal can reduce the risk of expansion and improve clinical outcome. For those taking coumarins, the best available evidence suggests that intravenous vitamin K combined with four-factor prothrombin complex concentrate (4F-PCC) is the most rapid and effective regimen to restore hemostasis. For those on dabigatran, the highest quality data available for reversal are for idarucizumab, although it is not yet clear whether patients derive clinical benefit from this reversal. In the absence or failure of idarucizumab, activated prothrombin complex concentrate (aPCC) is recommended. For those on factor Xa inhibitors, the ideal reversal agent is not clear. Many providers use 4F-PCC or aPCC, but more specific agents are in clinical trials and may soon be available. In addition, the half-lives of the non-vitamin K antagonists are relatively short compared with warfarin, and so some patients may not have a clinically relevant coagulopathy at the time of presentation. Overall, the optimal reversal agent, when one is required, is a function of which anticoagulant the patient is taking.

Evaluation of andexanet alfa and four‐factor prothrombin complex concentrate (4F‐PCC) for reversal of rivaroxaban‐ and apixaban‐associated intracranial hemorrhages

“…Several observational cohort studies found that 4F-PCC at a dose range of 25-50 units/kg achieves effective hemostasis in 65% to 94.7% of patients with oral FXa inhibitor-associated ICH. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Comparatively, excellent or good hemostasis was achieved in 80% of patients treated with andexanet alfa in the ANNEXA-4 trial, with a corresponding 92% reduction in apixaban and rivaroxaban levels after administration. 32 However, ANNEXA-4 exclusion criteria may not be representative of true clinical practice, as ethical considerations arise when restricting therapy from those with known risk factors for hematoma expansion, such as larger ICH volume or low GCS score at presentation, or low probability of survival at 30 days.…”

“…Good or excellent hemostatic effectiveness was achieved in 88.9% of patients in the andexanet alfa cohort and 60% of patients in the 4F‐PCC cohort. Several observational cohort studies found that 4F‐PCC at a dose range of 25‐50 units/kg achieves effective hemostasis in 65% to 94.7% of patients with oral FXa inhibitor‐associated ICH 14‐29 . Comparatively, excellent or good hemostasis was achieved in 80% of patients treated with andexanet alfa in the ANNEXA‐4 trial, with a corresponding 92% reduction in apixaban and rivaroxaban levels after administration 32 .…”

“…13 Off-label use of 4F-PCC for this indication suggests effective hemostasis can be achieved in 65% to 94.7% of patients with oral FXa inhibitor-associated ICH. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Comparatively, andexanet alfa is a recombinant human FXa decoy protein that binds directly to rivaroxaban and apixaban to reverse their anticoagulant effect. 8 However, despite a reported 92% reduction in anti-FXa activity at the end of the andexanet alfa bolus administration, clinician concerns regarding its efficacy and superiority were raised given its short duration of action and noted limitations in the open-label single arm clinical trial.…”

“…Justification for off‐label use of 4F‐PCC, which replaces factor II, VII, IX, and X, is that it may bypass the anticoagulant effect of oral FXa inhibitors through stimulation of thrombin formation 13 . Off‐label use of 4F‐PCC for this indication suggests effective hemostasis can be achieved in 65% to 94.7% of patients with oral FXa inhibitor‐associated ICH 14‐29 . Comparatively, andexanet alfa is a recombinant human FXa decoy protein that binds directly to rivaroxaban and apixaban to reverse their anticoagulant effect 8 .…”

Warfarin-Related Unilateral Spontaneous Hyphema

“…Bu kanamalar cilt hematomu veya subkonjonktival kanama kliniğinde olabileceği gibi intraserebral veya epiglottik kanamalar gibi ciddi morbidite ve mortalite risklerini de beraberinde getirebilir. [4][5][6][7] Hifema, klinik pratiğimizde sıklıkla künt okü-ler travma sonucunda rastladığımız bir durum olmasına rağmen, nadiren warfarin gibi oral antikoagülan kullanımına bağlı, travma öyküsü olmaksızın da karşımıza çıkabilmektedir. Literatürde bu şekilde bildirilmiş olgu sayısı son derece sınırlı-dır.…”