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WA Fricke, KM Brinkhous, JB Garris and HR Roberts
An acquired inhibitor of von Willebrand factor (vWF) activity occurring in
a patient with benign gammopathy and von Willebrand syndrome (vWS) has been
partially characterized. The inhibitor-induced syndrome resulted in low to
undetectable plasma levels of vWF/ristocetin, vWF/botrocetin, FVIIIR:Ag,
and FVIII:C with a normal to slightly prolonged bleeding time. Platelet vWF
was normal. Intensive and continuous infusion of a heat-treated factor VIII
concentrate (Hemofil- T, Hyland, Glendale, Calif) elevated the FVIII:C
plasma levels to about 100%, with an increase in FVIIIR:Ag levels to about
340% and vWF/ristocetin levels to about 40%, much lower than expected based
on the dose of Hemofil-T and its content of vWF and FVIII:C activities. The
inhibitor bound to staphylococcal protein A (SpA) with high affinity,
indicating an IgG antibody (Ab). An assay for the vWF-binding capacity was
developed on the basis of absorption of the Ab from serially diluted plasma
by SpA and removal of vWF and FVIII:C activities from normal plasma by the
SpA-Ab complex. The Ab-binding site was on the vWF component of the factor
VIII complex. The Ab was unable to bind isolated FVIII:C. The combined use
of the new vWF- binding assay and a battery of tests for inhibition of
vWF-dependent platelet aggregation with ristocetin (which detects high
molecular weight vWF), with botrocetin (which detects high and low
molecular weight vWF), and with platelet-aggregating factor (which detects
high molecular weight vWF) provided a means of analysis of Ab effect on in
vitro vWF function. Using these tests, a comparison was made of the effects
of the vWS Ab with those of an Ab inhibitor occurring in homozygous von
Willebrand's disease. The Ab of the vWS patient had weak inhibitory action
on vWF/ristocetin without having an effect on vWF/botrocetin and
platelet-aggregating factor, a high titer vWF- binding capacity, and no
anamnestic response following concentrate therapy. These findings
contrasted with those of the Ab occurring in inhibitor von Willebrand's
disease in which vWF inhibitor and binding values were similar, with a
strong anamnestic response. The findings indicate that the vWS Ab binds to
an epitope on the molecular vWF in such a way that causes only limited
inhibition of vWF/ristocetin function and no inhibition of vWF/botrocetin
function, suggesting that these two functional domains are at separate
sites.
This article has been cited by other articles:
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| Copyright © 1985 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
