Immunologic Studies in von Willebrand's Disease

Abstract

A B S T R A C T Antihemophilic globulin (AHF, factor VIII) levels were measured by a standard coagulation assay and by an immunological technique before and serially after infusion of fresh frozen plasma or cryoprecipitate into patients with von Willebrand's disease. Initial levels of AHF, measured both as procoagulant and as antigen, were low. Immediately after transfusions, the rise in levels of AHF-like antigen was compatible with the quantity of antigen present in the infused plasma or cryoprecipitate. Thereafter, levels of antigen declined rapidly and reached preinfusion values in approximately 24 hr. In contrast, procoagulant activity remained elevated, and sometimes continued to rise, for longer periods of time. One possible explanation of this finding is that the AHF molecule produced by patients with von Willebrand's disease, in response to transfusion of as yet unidentified factors, lacks the antigenic site associated with the normal AHF molecule or the inactive molecule produced by patients with hemophilia A.

Macromolecular factor VIII complex: functional and structural heterogeneity observed in von Willebrand swine with transfusion.

“…These studies extend earlier findings on the transfusion response of subjects with vWD, human (8,(15)(16)(17)(18)(19) and swine (9,10,20,21 (20), but not tocorrect the bleeding time. Normal plasma infused in swine (9) …”

“…Elution buffer was 0.05 M Tris-HC1, pH 7.2. Sample size was 0.5 ml, fractions were collected in 0.5-ml aliquots, and the flow rate was 8 The distribution patterns of AHF on agarose gel chromatography and on sucrose density gradient ultracentrifugation were compared in plasmas collected from pigs with vWD 1, 48, and 120 hr after infusion. Normal porcine plasma and plasma from swine with vWD before infusion similarly studied served as controls.…”

Cyclical Changes in Coagulation Factors Associated with the Use of Progestational Agents

“…A dissociation between activity and antigen levels is also seen following the administration of cryoprecipitate in von Willebrand's disease [2], and it may be that the portion of the factor VIII molecule containing the active site is responsive to oestrogen-progestogen levels, whereas the portion, containing the antigenic determinant for the antibody is not. These observations are also relevant to assays of factor VIII activity and antigen in potential carriers of haemophilia A, as fluctuations related to oral contraceptives could obscure activity/antigen ratios.…”

Molecular Immunology of Factor VIII

“…The rise in level of the von Willebrand's disease an tigen was compatible with the quan tity of antigen present in the infused plasma or cryoprecipitate and declined rapidly, reaching pre-infusion of values in approximately 24 hr. However, Factor VIII procoagulant activity remained elevated and sometimes continued to rise for longer periods of time, reaching levels considerably greater than that accounted for by the amount infused (26,27).…”

“…Of particular note is the response to infusions of normal plasma or Factor VIII concentrates, which produce an immediate rise in Factor VIII coagulant activity in the plasma of the hemophilic, an activity with a half-life of 12-14 hr. In contrast, infusion of Factor VIII concen trates or plasma into in dividuals with von Willebrand's disease is followed by a gradual rise in Factor VIII coagulant activity, sometimes not reaching a maximum for 24 hr and remain ing at an increased level for as long as five days (24)(25)(26)(27). In addition, the infusion of hemophilic plasma-containing no Factor VIII coagulant activity-is followed by a rise of Factor VIII coagulant activity in the plasma of individuals with von Willebrand's disease, although the reverse is not true.…”