Reduced Requirement for Prothrombin Complex Concentrate for the Restoration of Thrombin Generation in Plasma from Liver Transplant Recipients

BACKGROUND: Plasma transfusion remains the mainstay hemostatic therapy during liver transplantation (LT) in most countries. However, a large volume is required for plasma to achieve clinically relevant factor increases. Prothrombin complex concentrate (PCC) is a low-volume alternative to plasma in warfarin reversal, but its efficacy has not been well studied in LT. METHODS: Blood samples were collected from 28 LT patients at baseline (T 0) and 30 minutes after graft reperfusion (T 1). Factor X and antithrombin levels were measured. Ex vivo effects of PCC (0.2 and 0.4 IU/mL) and 10% volume replacement with normal plasma were compared in LT and warfarin plasma by measuring lag time, thrombin peak, and endogenous thrombin potential (ETP) using thrombin generation (TG) assay. RESULTS: Coagulation status was worsened at T 1 as international normalized ratio increased from 1.7 to 3.0, and factor X was decreased from 49% to 28%. TG measurements showed normal lag time and ETP at T 0 and T 1, but low-normal peak at T 0, and below-normal peak at T 1. Both doses of PCC increased peak and ETP, while 10% volume plasma had minimal effects on TG. Thrombin inhibition appears to be very slow after adding 0.4 IU/mL of PCC in LT plasma due to low antithrombin. The same doses of PCC and plasma were insufficient for warfarin reversal. CONCLUSIONS: Reduced TG in LT can be more effectively restored by using PCC rather than plasma. The required doses of PCC for LT patients seem to be lower than warfarin reversal due to slow thrombin inhibition