Different Heparin Contents in Prothrombin Complex Concentrates May Impair Blood Clotting in Outpatients With Ventricular Assist Devices Receiving Phenprocoumon

ObjectivesProthrombin complex concentrates (PCCs) are used to rapidly reverse anticoagulation by oral vitamin K antagonists. They differ in the content of clotting factors, endogenous anticoagulants, and heparin. The authors hypothesized that PCCs’ specific heparin content may compromise the hemostatic effect.DesignProspective ex-vivo investigation.SettingUniversity hospital.ParticipantsVenous blood samples were obtained from 8 patients with implanted ventricular assist devices who also were receiving phenprocoumon.InterventionsFour different 4-factor PCCs were added to patient blood to attain a calculated increase in prothrombin time by 20%, 40%, and 60% greater than baseline in paired experiments.Measurements and Main ResultsClotting was measured using thromboelastometry and endogenous thrombin potential. Two heparin-containing PCCs prolonged the clotting times in a concentration-dependent manner compared with baseline (p<0.01) and compared with PCCs containing significantly less or no heparin (p<0.01). The PCCs containing low or no heparin enhanced the area under the curve of thrombin generation and peak thrombin several fold relative to the heparin-containing PCCs (p<0.01). One of the PCCs containing heparin even decreased peak thrombin generation by ~90% compared with baseline (p<0.01). PCC with low or no heparin shortened the lag phase (p<0.01), whereas 1 heparin containing PCC prolonged the lag phase by 66% (p<0.01).ConclusionsPhysicians should be aware of the differences in heparin contents. Extrapolation of results from one agent to other PCC preparations may be difficult. Patients with an implanted left ventricular assist device and anticoagulated with vitamin-K antagonists could benefit from the use of PCC with low heparin content when surgery or bleeding requires emergency reversal. Further clinical studies are warranted.