Key result
In vitro, 3-factor PCC was as effective as 4-factor PCC in reversing vitamin K antagonists based on thrombin generation and EXTEM, but required higher doses to normalize INR when baseline INR was 3-4.
Why the study?
The efficacy of three-factor prothrombin complex concentrates in reversing vitamin K antagonists remains a matter of debate.
Does 3-factor PCC reverse vitamin K antagonist anticoagulation as effectively as 4-factor PCC in vitro?
Does 3-factor PCC reverse vitamin K antagonist anticoagulation as effectively as 4-factor PCC in vitro?
In-vitro, 3-factor PCC is as effective as 4-factor PCC in reversing oral anticoagulation based on thrombin generation and thromboelastometry, but not based on INR.
In-vitro PCC comparisons in VKA patients remain inconclusive; leaves open clinical equivalence of three- versus four-factor products.
: The efficacy of three-factor prothrombin complex concentrates (PCCs) in the reversal of vitamin K antagonists is still a matter of debate. We compared the 'in-vitro' effect of three PCCs (one three-factor and two four-factor) on international normalized ratio (INR), thrombin generation and thromboelastometry of patients at different degrees of anticoagulation with vitamin K antagonist. We tested three concentrations of PCC (0.5, 1 and 1.5 U/ml) in six patients: three (INR 2.0-2.9) and three (INR 3.0-4.0). In this preliminary phase, we determined the lowest effective dose for a target INR less than 1.5 and to normalize endogenous thrombin potential and clotting time in EXTEM assay. In the validation phase, we tested the effect of the newly determined lowest effective PCC dose on samples of 40 (INR 2.0-2.9) and 20 (INR 3.0-4.0) patients. The minimum efficacious dosage to achieve the target INR with three-factor PCC (3-PCC) was 0.5 (INR 2.0-2.9) and 1.5 U/ml (INR 3.0-4.0). Four-factor PCCs (4-PCCs) achieved target INR with the lowest dose (0.5 U/ml) independently of baseline INR. Thrombin generation endogenous thrombin potential and EXTEM clotting time achieved normal values with the lowest dose (0.5 U/ml) of either 3-PCC or 4-PCC independently of baseline INR. Data observed in the preliminary phase were confirmed in the validation phase. 3-PCC appears to be as effective as 4-PCC in reversing oral anticoagulant treatment based on thrombin generation and EXTEM data, but not INR data, at least in the range of INR considered in our study. Further studies are needed to address the clinical implications of our results.
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Spiezia et al. (2020) studied Anticoagulation with vitamin K antagonists (n=66). Three-factor prothrombin complex concentrate (3-PCC) vs. Four-factor prothrombin complex concentrates (4-PCCs) was evaluated on Target INR less than 1.5, normalized endogenous thrombin potential, and EXTEM clotting time. In vitro, 3-factor PCC was as effective as 4-factor PCC in reversing vitamin K antagonists based on thrombin generation and EXTEM, but required higher doses to normalize INR when baseline INR was 3-4.
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