These authors contributed equally to this manuscript.
Role of coagulation FVIII in septic peritonitis assessed in hemophilic mice
Article first published online: 24 NOV 2005
Journal of Thrombosis and Haemostasis
Volume 3, Issue 12, pages 2738–2744, December 2005
How to Cite
SCHOENMAKERS, S. H. H. F., BRÜGGEMANN, L. W., GROOT, A. P., MAIJS, S., REITSMA, P. H. and SPEK, C. A. (2005), Role of coagulation FVIII in septic peritonitis assessed in hemophilic mice. Journal of Thrombosis and Haemostasis, 3: 2738–2744. doi: 10.1111/j.1538-7836.2005.01649.x
- Issue published online: 24 NOV 2005
- Article first published online: 24 NOV 2005
- Received 26 July 2005, accepted 30 August 2005
- factor FVIII;
Summary. Background: Inhibition of blood coagulation appears to be an important therapeutic strategy to improve the outcome in sepsis. However, the beneficial effect of anticoagulant treatment in sepsis is solely based on experimental data using inhibitors of the extrinsic coagulant pathway. The role of the intrinsic pathway of coagulation in the pathogenesis of sepsis has not been explored yet. Objective: In the current study, we contribute to determine the role of factor (F)VIII, the key player of the intrinsic coagulant pathway, on host defense against peritonitis. Method: Hemizygous FVIII-deficient mice and their wild-type littermates were challenged with 1 × 104 bacteria in a septic peritonitis model. Results: The intraperitoneal injection of Escherichia coli led to growth and dissemination of bacteria and provoked an inflammatory response as evident from elevated cytokine levels, increased cell influx into tissues, liver necrosis, and endothelialitis resulting in mortality. The FVIII-deficient genotype slightly reduced bacterial outgrowth but had no effect on markers of inflammation and/or survival. In addition, FVIII-deficient mice showed profound activation of coagulation, thereby improving the hemophilic phenotype of FVIII-deficient mice. Conclusion: FVIII deficiency slightly modifies host defense in septic peritonitis in mice, but does not influence the final outcome of peritonitis. Therefore, we question the importance of the intrinsic coagulant pathway during sepsis.