Biochemical characteristics of therapeutic plasma concentrates used in the treatment of von Willebrand disease.
Therapeutic plasma concentrates containing von Willebrand factor (vWF) lack the largest, most hemostatically active multimers. In order to evaluate whether this abnormality results from proteolysis during manufacturing, we have analyzed the subunit structure of vWF in 21 commercial products and found a marked reduction in the relative content of intact 225 kD subunit, paralleled by an increase in the proteolytic fragments normally present in plasma, particularly that of 176 kD. There was no heightened vWF fragmentation in blood-bank cryoprecipitate prepared from platelet-poor, single-donor plasma; in contrast, there was a marked degree of fragmentation in cryoprecipitate prepared from pooled plasmapheresis plasma representing the starting fraction for the production of commercial concentrates. In cryoprecipitate prepared experimentally from plasma containing varying numbers of platelets, the degradation of vWF was proportional to the platelet count but was greatly diminished by adding protease inhibitors to plasma. On the basis of these findings, we postulate that the loss of the largest vWF multimers in commercial concentrates results from the use of poorly centrifuged plasmapheresis plasma containing an excessive number of residual platelets and leukocytes.
Mannucci
P M
PM
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Milano, Italy.
D016913:Blood Component Transfusion; D006801:Humans; D010949:Plasma / Q000737:chemistry*; D014842:von Willebrand Diseases / Q000628:therapy*