Heparin-induced effects of prothrombin complex concentrates in thromboelastometry

Prothrombin complex concentrates (PCC) are currently used to treat congenital or acquired coagulation factor deficiency. In case of serious bleeding caused by new oral anticoagulant agents, reversing treatment with PCC is under debate. PCC preparations mostly contain heparin to prevent thromboembolic events. In factor VIII and IX deficient plasma, Takeyama et al. observed in vitro a heparin effect at appropriate concentrations of PCCs. The aim of the present experiment was to investigate the heparin effect of four factor-PCC at clinically relevant concentrations in whole blood. In an in vitro experiment, we compared the PCC preparation used in the experiments of Takeyama with a high heparin content to a new heparin-free PCC preparation.

After ethics committee approval and written informed consent, the citrated whole blood was obtained from ten healthy volunteers. We tested heparin-containing Prothromplex(®) and heparin-free Cofact(®) at concentrations of 0.31, 0.63, and 1.25 IU/ml. Protamine was added to another set of samples (1:1 heparin:protamine). We used the NATEM test in the rotational thromboelastometer ROTEM(®).

In the heparin PCC preparation, we observed a significant (p < 0.001) concentration-dependent prolongation in CT and CFT, even at the lowest concentration. MCF was also significantly reduced. The heparin effect was reversible by protamine. The heparin-free PCC did not affect the onset of coagulation. The interpretation of the alpha-angle showed no increased thrombus formation in heparin-free PCC preparation.

Our results extend the report of Takeyama et al. At clinically relevant PCC concentrations, the heparin effect was significant in thromboelastometry. The heparin content of PCCs should be considered in clinical routine.