A New Double Virus Inactivated 4-Factor Prothrombin Complex Concentrate (4F PCC)

Abstract number: P0060

Griffin B, Murphy A, Stefaniuk K, Foster P, Morrison L, MacGregor I, Bienek C

Prothrombin Complex Concentrates (PCC) are used clinically for the reversal of anticoagulant therapy which inhibits the synthesis of the vitamin K dependent coagulation factors II, VII, IX and X in the liver. The current SNBTS product HT DEFIX^® is licensed for this indication and has an excellent safety record with respect to both virus transmission and thrombogenicity. However, it has only a single virus inactivation step, heat treatment at 80°C for 72 hours, and contains only three of the four coagulation factors of the prothrombin complex, factors II, IX and X. As it does not contain factor VII, the use of HT DEFIX is normally supplemented with Fresh Frozen Plasma (FFP). Therefore we have developed a new 4 Factor PCC with two distinct virus inactivation steps: solvent/detergent treatment and terminal dry heat treatment at 80°C for 72 hours. This product has the additional advantage of removing the need for administration of FFP, thus eliminating the risks associated with the use of single donor UK plasma. The product contains a nominal 500 iu FIX/vial, has a FVII content of 250–300 iu/vial and complies with the Ph. Eur. monograph (0554) for Human Prothrombin Complex, without the addition of Heparin or ATIII. Initial studies have demonstrated the effectiveness of the virus inactivation steps against both lipid-enveloped (PRV and BVDV) and non-enveloped viruses (HAV >=5.26 log₁₀ and CPV up to >=5.0 log₁₀ over FD + HT). In vivo testing in the Wessler rabbit model has indicated a significantly lower thrombogenic potential than with the current HT DEFIX^® product (P < 0.05).