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Updated: Apr 29, 2026
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Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation
Published on: August 14, 2017
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Cellular Stress Induced by Plasma-Derived Factor VIII Products
Martin Brodde1, Anja Müller1, Beate Kehrel2
1Experimental and Clinical Hemostasis, Department of Anesthesiology, Intensive Care and Pain Therapy, University Hospital Münster, Germany ; OxProtect GmbH, Münster, Germany.
Summary
Plasma-derived factor VIII (pdFVIII) products induced cellular stress in vitro, unlike recombinant FVIII (rFVIII). This suggests potential clinical relevance for hemophilia A patients due to chronic cell irritation.
Area of Science:
- Biochemistry
- Cell Biology
- Hematology
Background:
- Protein impurities were previously identified in plasma-derived factor VIII (pdFVIII) products.
- The clinical relevance of these impurities requires further investigation.
Purpose of the Study:
- To compare the effects of pdFVIII and recombinant factor VIII (rFVIII) on cellular stress induction.
- To determine if protein impurities in pdFVIII have clinical relevance.
Main Methods:
- In vitro evaluation of cell stress sensors using 2 pdFVIII and 1 rFVIII product.
- Assessment of microparticle formation in treated cells.
- Measurement of mitochondrial membrane potential in cells treated with clinically relevant concentrations.
Main Results:
- Both pdFVIII products induced microparticle formation in platelets, monocytes, and granulocytes.
- pdFVIII products, but not rFVIII, significantly depolarized the mitochondrial membrane potential.
- rFVIII product did not induce microparticle formation or affect mitochondrial membrane potential.
Conclusions:
- The tested pdFVIII products induced cellular stress in vitro.
- rFVIII product did not induce cellular stress.
- Chronic activation of cellular stress defense systems by pdFVIII may have clinical consequences for hemophilia A patients.
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