Prothrombin Complex Concentrate, a General Antidote for Oral Anticoagulation

Abstract

Prothrombin complex concentrate (PCC) is used for the rapid reversal of vitamin K antagonist (VKA) anticoagulation. PCC is also applicable in situations requiring rapid reversal of anticoagulation by non-vitamin K antagonist direct thrombin and factor Xa inhibitor oral anticoagulants (NOACs), thereby making PCC a general antidote for oral anticoagulation. In this chapter, the composition of different PCC brands is reviewed and a negative effect of heparin supplement in some products is recognized. Mode of action of anticoagulation reversal by PCC is explained. Dosage and clinical efficacy, two closely related issues, are discussed and based on reviewed data recommendations are given that may prohibit too low PCC dosing, especially in NOAC anticoagulation. Use of unsuitable laboratory assays has raised needless controversy as to the applicability of PCC to reverse anticoagulation by NOACs, in particular dabigatran. In this chapter, various laboratory assays are evaluated for their applicability in monitoring reversal of anticoagulation.

Reversing direct factor Xa or thrombin inhibitors: Factor V addition to prothrombin complex concentrate is beneficial in vitro

“…The thrombin generation assay is a generally accepted laboratory method to assess the reversal of DOAC anticoagulation. 5 , 29 As a first approach to study this reversal, normal plasma was treated with rivaroxaban to prolong the thrombin generation lag time to 340% (Figure 1A ) and to reduce thrombin peak (Figure 1B ) and ETP level (Figure 1C ) to 12% and 53%, respectively. In a dose‐dependent manner, the supplementation of PCC to this rivaroxaban‐treated plasma restored the ETP (Figure 1C ) and improved the thrombin peak level (Figure 1B ), whereas it hardly affected the lag time (Figure 1A ).…”

“… 36 PCC dosing was based on FIX international activity units (U). 5 Relative content of the other vitamin K‐dependent coagulation factors (U/U FIX) in the used PCC batch was: FII 0.99, FVII 0.51, FX 0.86, protein S 0.16, and protein C 0.88. For FV, this was <0.01.…”

<p>Successful Cerebral Hemorrhage Control with Prothrombin Complex Concentrate in a Patient on Edoxaban Therapy: A Case Report</p>

“…4F-PCC, on the other hand already contains human factors II, VII, IX, and X that increase the concentration of vitamin K dependent coagulation factors above normal generating more factor Xa and thrombin that escapes from DOAC inhibition, resulting in increased feedback amplification of the coagulation processes. 9 In a Phase I study in healthy volunteers, intravenous 4F-PCC dose-dependently reversed the effects of edoxaban 60 mg, and suggest that 4F-PCC represents a readily available option in cases where rapid reversal of edoxaban anticoagulation is essential. The double-blind, randomized, placebo-controlled, study determined the reversal effect of descending doses of 4F-PCC on bleeding duration and bleeding volume following edoxaban treatment.…”

“…The complex of tissue factor with factor-VIIa activates the coagulation factors IX, X, (IXa, Xa) that lead to the activation of prothrombin in thrombin thus reversing factor Xa inhibition. 9 Edoxaban is the only anti-Xa inhibitor agent to have data on the effects of four-factor prothrombin complex concentrate (4F-PCC) on the reversal of bleeding. In a study of healthy subjects, the administration of a 4F-PCC at 50 IU/kg has shown to reverse the effects of edoxaban 30 mins after completing the infusion.…”

An Appraisal of Antidotes’ Effectiveness: Evidence of the Use of Phyto-Antidotes and Biotechnological Advancements

“…These coumarins act by reinstating the active vitamin K form by inhibiting vitamin K reductase [41,42]. Dosage in form of an international normalized ratio (INR) which serves as a guide remains a subject of debate and needs close monitoring [43]. However, a new class of oral, non-vitamin K anticoagulants which do not require much monitoring or dose adjustment include dabigatran, rivaroxaban, edoxaban and apixaban.…”