Manufacturing of a prothrombin complex concentrate aiming at low thrombogenicity

The paper describes the production of a prothrombin complex concentrate (PC C) with high virus safety and a well-balanced content of vitamin K-dependen t clotting factors and inhibitors. Solid-phase extraction is followed in a second step by optimized anion exchange chromatography using a radial colum n. A step for virus removal by nanofiltration is introduced in addition to the solvent/detergent step. By speeding up the chromatographic step, the pe riod of time required for production is reduced considerably. The activitie s of the four vitamin K-dependent clotting factors II, VII, IX and X are in ratios of about 1:1:1:1. Protein C, Protein S, and Protein Z are also pres ent in therapeutically effective concentrations. The product shows no throm bogenicity, in neither in vivo nor in vitro models. Clinical investigations show that the PCC is a safe and efficient preparation for the substitutive treatment of FIX or FVII in patients suffering from the respective deficie ncies. All bleeding episodes ha ire been efficiently controlled with relati vely low doses of the concentrate. The surgical procedures have been conduc ted without any problems in severely FIX and FVIII deficient patients. (C) 2000 Elsevier Science Ltd. All rights reserved.