The role of the spleen in regulating the plasma levels of factor VIII--von Willebrand's factor after DDAVP.

ABSTRACT

Organ transplantation and perfusion studied indicate that the spleen plays an important role in the regulation of plasma levels of factor VIII-von Willebrand's factor (FVIII-vWF). To better understand the mechanisms that regulate the FVIII-vWF increases after infusion of 1-deamino-8-D-arginine vasopressin (DDAVP), we have measured factor VIII coagulant activity (FVIIIC) and antigen (FVIIICAg) and von Willebrand's factor antigen (vWFAg) and ristocetin cofactor (vWFRCof) in 9 asplenic subjects with normal baseline concentrations, in 7 asplenic subjects with high concentrations, and in 14 normal controls with intact spleens. In "normal" aasplenics, all the FVIII-vWF-related measurements increased significantly over baseline values, indicating that responsiveness to DDAVP is not abolished by splenectomy. The maximal vWFAg and vWFRCof responses were no different from those of normal controls, suggesting that DDAVP releases vWF from storage sites other than the spleen. The FVIIIC response was significantly lower than in normal controls, but FVIIICAg did not differ, making FVIIICAg higher than FVIIICAg in "normal" asplenics. These findings suggest that the spleen, rather than being a storage site for FVIII, is the organ in which a partially inactive form of FVIII acquires full coagulant activity. In "high" asplenics, all the FVIII-vWF-related measurements increased less than in "normal" splenics, indicating that long-term elevations of plasma concentrations of FVIII-vWF are accompanied by decreased release from those storage pool(s) mobilized by DDAVP.