The role of the spleen in regulating the plasma levels of factor VIII--von Willebrand's factor after DDAVP.
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 (FVIII:C) and antigen (FVIII:CAg) and von Willebrand's factor antigen (vWF:Ag) and ristocetin cofactor (vWF:RCof) 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 vWF:Ag and vWF:RCof responses were no different from those of normal controls, suggesting that DDAVP releases vWF from storage sites other than the spleen. The FVIII:C response was significantly lower than in normal controls, but FVIII:CAg did not differ, making FVIII:CAg higher than FVIII:CAg 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.
D000293:Adolescent; D000328:Adult; D000941:Antigens / Q000032:analysis; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001779:Blood Coagulation Factors / Q000032:analysis*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D005169:Factor VIII / Q000032:analysis* / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012310:Ristocetin / Q000032:analysis; D013154:Spleen / Q000502:physiology*; D013156:Splenectomy; D014841:von Willebrand Factor / Q000032:analysis*
D000941:Antigens; D001779:Blood Coagulation Factors; D014841:von Willebrand Factor; D001127:Arginine Vasopressin; D012310:Ristocetin; D005169:Factor VIII; D003894:Deamino Arginine Vasopressin