Are quality differences responsible for different adverse reactions reported for SD‐plasma from USA and Europe?

Abstract

Thromboembolic adverse reactions reported after transfusion of SD-plasma in the United States (US) prompted us to perform a comparative study with SD-plasma from the US and the European (EU) market. In SD-plasma from US, residual tri-N-butyl phosphate was found, and citrate concentrations were lower than in EU-plasma. Except for substantial losses of FV, FVIII and antiplasmin found for all SD-plasmas, clotting factor activities were mainly retained. However, for SD-plasma from US, markedly elevated concentrations of lipoprotein (a) [Lp(a)], fibrin monomer and a particularly high degree of complement activation (C3a des-Arg) were observed. Furthermore, pronounced differences were found for protein S. Although SD-plasma pools from US contained nearly normal concentrations of free and bound protein S antigen, protein S activities were almost completely absent. In contrast to this, SD-plasma from EU showed a moderate loss of both protein S activity and free antigen. Antitrypsin inhibitor activities were much more diminished in SD-plasma from US than from EU. In view of a possible thrombogenicity of SD-plasma from US, the loss of protein S and elevated Lp(a) concentrations could be of significance. The very high levels of C3a des-Arg in US plasma could possibly have an additional effect, through priming platelet activation after transfusion.

Proteomic analysis of microvesicles from plasma of healthy donors reveals high individual variability

“…Another important protein associated to circulating-MVs with important implications in the modulation of coagulation and platelet activation is the component 3 of the complement (C3). Thus, high levels of this protein in plasma have been pointed as one of the factors responsible for some thromboembolic adverse reactions reported after transfusion [36]. These and other examples of associations between different pathological conditions and proteins contained in plasma circulating-MVs arise the necessity to further investigate, design and develop quality controls for this plasma component, in special towards those samples allocated to therapeutic applications.…”

Thrombin Generation Capacity of Methylene Blue-Treated Plasma Prepared by the Theraflex MB Plasma System

“…All batches of these units had passed the tests at the Paul Ehrlich Institute necessary for official batch release. Further data on clotting parameters have been published recently by SalgeBartels et al [17].…”

Pathogen inactivation

“…Such changes in the preparation methodology have a noticeable effect in the coagulation factor profile of the final product. Thus, in comparison to the European product, protein S activity and plasminogen activation inhibitor type 1 are almost absent, and the citrate concentration lower, in the US product [20].…”