Background: Reversal of severe bleeding under factor Xa inhibitor therapy requires either therapy with the specific antidote andexanet alfa or prothrombin complex concentrate (PCC). All PCCs are standardised and administered according to the quantity of factor IX, but there are considerable differences between PCCs in the quantities of coagulation factors II, VII, and X.

Aims: This study aims to explore the impact of different 4F-PCCs ex vivo using human blood treated with FXa inhibitors, as prediction of these impact on coagulation status due to the various quantities of coagulation factors and inhibitors in these products. Therefore, four different 4F-PCCs and activated PCC (aPCC) were be compared for their antagonizing effect.

Methods: Blood samples from 10 healthy volunteers were spiked with rivaroxaban (RIVA). Four different 4F-PCCs (Beriplex, CSL Behring; Octaplex, Octapharma; Cofact, Biotest; Prothomplex, Baxalta) and aPCCs (FEIBA, Baxter) were added at clinical recommended doses (25 and 50 U/kg body weight). Various laboratory assays including PT, aPTT, and a thrombin generation assay (CAT) were applied to measure the impact of PCC/aPCC.

Results: Increasing the concentration of RIVA, decreased significantly thrombin generation potential (ETP, peak high) and prolonged the lag time. At low concentrations of RIVA (37,5 ng/mL, 75 ng/ml) all PCCs and aPCC restored ETP, but the peak did not reach baseline (figure 1).The addition of PCCs at high RIVA concentrations (150 ng/ml, 300ng/ml) had only small effects on thrombin generation potential. The prolonged lag time was only shortened by aPCC.

Conclusions: Restoration of thrombin generation following anticoagulation with RIVA showed no significant difference between commercially available PCCs. Higher concentrations of RIVA (≥150 ng/ml) cannot be reversed using PCC. The impact on the lag time after aPCC substitution is probably related to FVIIa.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/investigation-of-several-four-factor-pccs-to-restore-thrombin-generation-following-anticoagulation-with-rivaroxaban-ex-vivo-study/