Cleavage of factor VIII light chain promotes a change in the conformation of the C2 domain that facilitates dissociation from VWF and enhances the affinity of factor VIIIa for anionic phospholipid surfaces (Saenko et al. 1998).
Membrane-bound thrombin-activated factor VIII (fVIIIa) functions as a cofactor for factor IXa in the factor Xase complex. Factors VIIIa and IXa associate with anionic phospholipid surfaces with high affinity (Respective Kd values ?1 nM and ~15nM, Gilbert et al. 1990, Mertens & Bertina 1984, Greengard et al. 1986). Studies using physiologic surfaces provide evidence for coordinated binding interactions of the enzyme, cofactor and substrate to discrete surface structures. For example, the presence of both (active site-modified) factor IXa and factor X increased both the number and the affinity of binding sites on activated platelets for factor VIIIa (Ahmad et al. 2000). However classical receptors for the constituents of factor Xase have not been identified (Fay 2004).