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 Blood, 15 July 2008, Vol. 112, No. 2, pp. 240-249.
Prepublished online as a Blood First Edition Paper on May 9, 2008; DOI 10.1182/blood-2008-02-124941.

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Submitted February 26, 2008
Accepted April 14, 2008

Dynamics of factor VIII interactions determine its immunological fate in hemophilia A

Sebastien Lacroix-Desmazes*, Ana-Maria Navarrete, Sebastien Andre, Jagadeesh Bayry, Srinivas V. Kaveri, and Suryasarathi Dasgupta

INSERM UMR S 872, Universite Pierre et Marie Curie, Paris, France

* Corresponding author; email: sebastien.lacroix-desmazes{at}crc.jussieu.fr.

Pro-coagulant factor VIII (FVIII) is either produced endogenously under physiological conditions, or administered exogenously as a therapeutic hemostatic drug in patients with hemophilia A. In the circulation, FVIII interacts with a multitude of glycoproteins, and may be used for coagulation at the sites of bleeding, eliminated by scavenger cells or be processed by the immune system, either as a self-constituent or as a foreign antigen. The fate of FVIII is dictated by the immune status of the individual, the location of FVIII in the body at a given time-point, and the inflammatory microenvironment. It also depends on the local concentration of FVIII and of each interacting partner, and on the affinity of the respective interactions. FVIII, by virtue of its promiscuity, thus constitutes the core of a dynamic network that links the coagulation cascade, cells of the immune system and, presumably, the inflammatory compartment. We describe the different interactions that FVIII is prone to establish during its life cycle, with a special focus on players of the innate and adaptive immune response. Lessons can be learned from understanding the dynamics of FVIII interactions; lessons that should pave the way to the conception of long-lasting hemostatic drugs devoid of iatrogenic immunogenicity.


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S. Lacroix-Desmazes, J. D. Dimitrov, Y. Repesse, C. L. Eckhardt, P. W. Kamphuisen, K. Fijnvandraat, G. Yang, L. Yao, Z. Lu, F. Peyvandi, et al.
Inhibitors of Factor VIII in Hemophilia
N. Engl. J. Med., July 16, 2009; 361(3): 308 - 310.
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