Cellular Stress Induced by Plasma-Derived Factor VIII Products.
BACKGROUND
We previously identified protein impurities in plasma-derived factor VIII (pdFVIII) products. The goal of the current experiments was to determine whether these impurities might have clinical relevance, by comparing the effects of pdFVIII and recombinant FVIII (rFVIII) products on cellular stress induction.


METHODS
The in vitro outcomes on cell stress sensors of 2 pdFVIII products and 1 rFVIII product were evaluated. Microparticle formation was assessed in cells treated with the 3 products. Effects on the mitochondrial membrane potential were measured in cells treated with clinically relevant concentrations of each product.


RESULTS
Microparticle formation was induced in platelets by 1 pdFVIII product and in monocytes and granulocytes by both pdFVIII products; the rFVIII product did not affect microparticle formation. Both pdFVIII products, but not the rFVIII product, significantly depolarized the mitochondrial membrane potential.


CONCLUSIONS
The 2 pdFVIII products tested induced cellular stress in in vitro experiments. No such results were seen with the rFVIII product. Chronic activation of the cell stress defense system and chronic cell irritation may have clinical consequences for patients with hemophilia A.
Experimental and Clinical Hemostasis, Department of Anesthesiology, Intensive Care and Pain Therapy, University Hospital Münster, Germany ; OxProtect GmbH, Münster, Germany.
Martin
M
Brodde
Experimental and Clinical Hemostasis, Department of Anesthesiology, Intensive Care and Pain Therapy, University Hospital Münster, Germany ; OxProtect GmbH, Münster, Germany.
Anja
A
Müller
Experimental and Clinical Hemostasis, Department of Anesthesiology, Intensive Care and Pain Therapy, University Hospital Münster, Germany.
Beate
B
Kehrel
Cell stress; Factor VIII; Hemophilia; Plasma derived; Recombinant