Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists

Abstract

Prothrombin complex concentrates (PCCs) are recommended as the treatment of choice in warfarin-related coagulopathy. However, the risk of thromboembolic complications associated with their use is not well defined. We performed a meta-analysis to estimate the rate of thromboembolic complications in patients receiving vitamin K antagonists (VKAs) treated with PCCs for bleeding or before urgent surgery. Medline and Embase databases were searched. Two reviewers performed study selection and extracted data independently. Studies providing data on incidence of thromboembolic complications in VKA-treated patients were eligible for the study. Weighted mean proportion of the rate of thromboembolic complications and the mortality rate were calculated. Twenty-seven studies (1,032 patients) were included. Seven studies used 3-factor, and 20 4-factor PCCs. Twelve patients had a thromboembolic complication (weighted mean 1.4%; 95% CI 0.8-2.1), of which two were fatal. The incidence of thromboembolic events was 1.8% (95% CI 1.0-3.0) in patients treated with 4-factor PCCs, and 0.7% (95% CI 0.0-2.4) in patients treated with 3-factor PCCs. Total mortality rate was 10.6% (95% CI 5.9-16.6). In conclusion, our results suggest there is a low but quantifiable risk of thromboembolism in VKA-treated patients receiving PCCs for anticoagulation reversal. These findings should be confirmed in randomised, controlled trials.

Safety, pharmacokinetics and pharmacodynamics of idarucizumab, a specific dabigatran reversal agent in healthy Japanese volunteers: a randomized study

“…An increase in prothrombotic effect is a potential risk following reversal of anticoagulation; a meta‐analysis of trials in vitamin K antagonist–treated patients receiving prothrombin complex concentrates for anticoagulation reversal suggested a low but quantifiable risk of thromboembolism 15. It could not be determined whether this represents underlying risk or is a prothrombotic effect.…”

“…Owing to the relatively short half‐life of dabigatran (12‐14 hour),13 cessation of treatment and standard supportive care (eg, volume replacement) can be used to manage bleeding in many patients with adequate renal function, but this may be inadequate in emergency situations 13, 14, 15, 16…”

Specific antidotes for bleeding associated with direct oral anticoagulants

“…Thus, replenishment with factor concentrates is logical and has been shown to be beneficial in reversing vitamin K antagonist anticoagulant activity. [23][24][25][26] Conversely, patients on DOACs have normal levels of clotting factors in plasma, but enzymatic activity towards thrombus formation is directly blocked, making administration of factor concentrates less logical and beneficial.…”

Emergency neurosurgical care in patients treated with apixaban: report of 2 cases

“…e l s e v i e r . c o m / l o c a t e / a j e m administration has been associated with a considerable risk of thromboembolic events such as myocardial infarction [9]. Although both patients had no symptoms suggestive of thromboembolic events, this risk has to be taken into account when considering administration of PCC.…”