Markers of Blood Cell Activation and Complement Activation in Factor VIII and von Willebrand Factor Concentrates

BACKGROUND: Preparations of commercially available clotting factor VIII are complex protein mixtures. Most of them contain either von Willebrand factor or human serum albumin as stabilizers. The aim of the study was to quantify further proteins in twelve concentrates either of recombinant origin or derived from human plasma. METHODS: Proteins were separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Some proteins were quantified by ELISA. RESULTS: Recombinant clotting factor preparations showed fewer protein spots in the 2D-PAGE, than plasma-derived preparations. Proteins identified in some of the plasma-derived concentrates included up to 90 ng/IU of the anaphylatoxin C3a, up to 40 ng/IU of the platelet a-granule protein thrombospondin-1, up to 0.85 ng/IU of the platelet a-granule protein platelet factor 4, 3.5 ng/IU myeloperoxidase secreted by leukocytes and up to 0.05 ng/IU of the leukocyte-secreted protein a-defensin. The protein content differed between concentrates from different manufacturers. CONCLUSIONS: The origin of the plasma used to prepare the factor concentrates might influence the protein impurities in these products. It is unknown whether the impurities observed have long-term consequences for chronic inflammatory conditions.