Recent Reduction in Thrombogenic Enzyme Content of Prothrombin Complex Concentrates
In previous studies of prothrombin complex concentrates, it was demonstrated that there was a high content of potentially thrombogenic enzymes in the products from certain manufacturers, and that the enzyme conteat correlated closely with in vivo assays for thrombogenicity and with the observed incidence of thrombotic episodes following infusion (Thromb. Diath. Haemorrh. 33, 617, 1 975\Subsequently, it was shown that the thrombogenic enzymes could be generated by prolonged contact with DEAE-cellulose or calcium ions during preparation or later handling (Blood, 49, 159, 1977). In view of. these observations, efforts have been made to reduce the contact time of plasma fractions with either DEAE-cellulose or calcium ion during purification of these fractions for therapeutic use. In vitro assays for thrombogenic enzymes using the nonactivated partial thromboplastin time (NAPTT) were recently repeated on some of the currently available therapeutic materials. Assays were standardized and compared with previous results by using a provisional standard provided by Dr. David Aronson, Bureau of Biologies, USFDA. In the 1975 study, one manufacturer was identified as making a concentrate virtually free of thrombogenic enzyme. The concentrate currently being made by this manufacturer still does not significantly shorten the NAPTT. In the 1975 study, 2 manufacturers were shown to be making concentrates with high titers of thrombogenic enzyme. The current products of these two manufacturers contain detectable but significantly lower levels of thrombogenic enzymes. Thus it appears that for these two manufacturers, minor changes in production procedures have led to a product containing less potentially thrombogenic material.