Thrombin Generation Capacity of Prothrombin Complex Concentrate in an in Vitro Dilutional Model

There is a growing use of prothrombin complex concentrates (PCCs) for the treatment of trauma-induced coagulopathy, which is addressed to their propensity to increase thrombin generation. Despite considerable differences in composition of commercially available PCCs, there is lack of data investigating the procoagulant capacity of different PCCs.

The vitamin K-dependent coagulation factors, heparin, and antithrombin were assessed in five commercially available PCCs. The procoagulant potential of the PCCs was assessed in plasma and whole blood from 4 healthy donors by means of classical coagulation assays, thrombin generation assay and thromboelastometry. In order to reflect coagulopathy, whole blood was diluted with 20, 40, 60, and 80% Ringer's lactate solution.

The five different PCCs were characterised by comparable levels of factors II, VII, IX and X (all around 20–30 IU/mL), whereas the heparin (0 to 17.6 IU/mL) and antithrombin (0.06 to 1.29 IU/mL) levels were remarkably different between manufactures. In vitro dilution of blood induced a prolongation of the PT and aPTT, and attenuation of thrombin generation and ExTem induced thromboelastometry. Overall, non- or low-heparin containing PCCs restored the in vitro dilutional coagulopathy, whereas PCCs containing heparin has an anticoagulant effect. The thrombin generation assay showed to be the most sensitive method for assessment of PCC effects.

This study shows that most available PCCs are not balanced regarding their pro-and anticoagulants. The effect of measured differences in thrombin generation among different PCCs require further investigations to elaborate the clinical meaning in the treatment of trauma induced coagulopathy.

No relevant conflicts of interest to declare.