Calcium Prevents Enhanced Degradation of Factor VIII in the Condition of Motion

SIMPLE SUMMARY: In the present work, calcium was found to prevent degradation of factor VIII during intermittent motion. In addition, calcium supplementation in drinking water consumed by mice increased factor VIII in blood and striated muscle. The clinical relevance of this work is that oral calcium may be evaluated as a potential supportive therapy in hemophilia patients. Another aspect is that food additives with calcium may increase factor VIII level, which is known to contribute to both arterial and venous thrombosis. ABSTRACT: Background: Hemophilia A and B induce recurrent bleeding episodes, mainly in skeletal muscles and joints that are in intermittent motion. We have previously demonstrated that intermittent motion contributes to increased degradation of factors VIII and IX. Objectives: Given that calcium ions are known to enhance factor VIII–von Willebrand factor (vWF) interaction, the present study has investigated the role of these ions on factors VIII and IX in the condition of motion. Methods: The effects of calcium ions were assessed using purified proteins via Western blot, factor VIII activity, immunocytochemistry, and in Institute of Cancer Research (ICR) mice with no specific genetic background. Results: Calcium was found to prevent degradation of plasma-derived factor VIII but not that of factor IX, during intermittent motion. Calcium levels in the microcirculation of mouse striated muscles were elevated following movement, enabling prevention of factor VIII degradation in normal physiology. Calcium supplementation in drinking water increased factor VIII levels in blood and striated muscles of ICR mice during movement. Conclusions: calcium ions decrease factor VIII degradation in the condition of motion. Further research on the impact of calcium salt oral supplementation on hemophilia patients is warranted.