ABSTRACT
von Willebrand disease (vWD) is a bleeding disorder that results from defects in the
quality or quantity of von Willebrand factor (vWF), a glycoprotein essential for normal
thrombus formation. vWF circulates in plasma as multimers in sizes ranging up to 20,000
kd. The high molecular weight vWF (HMWvWF) multimers are most essential for primary
hemostasis, whereas the lower molecular weight multimers are less functionally active.
For many patients, the treatment of choice is factor replacement with a vWF/FVIII
concentrate, preferably one with a high content of HMWvWF multimers. Given that the
commercially available vWF/FVIII concentrates seem to differ substantially in their
biochemical properties as well as in their clinical efficacy, we did a comparative
study with 12 vWF/FVIII concentrates to investigate content and activities of FVIII
and vWF, as well as the content of HMWvWF multimers. The content of HMWvWF multimers
varied considerably among the 12 concentrates. The specific vWF activities, as assessed
by ristocetin cofactor activity (vWF:RCo) and collagen-binding activity (vWF:CB),
correlated well with the HMWvWF content of the products. Of the products tested, Haemate
P/Humate-P had the highest content of HMWvWF multimers (with a multimer pattern closest
to that of normal human plasma), the highest specific vWF activities, and the highest
values of vWF:RCo and vWF:CB per unit of FVIII:coagulant (C). The goal of bleeding
prophylaxis and treatment in type 2, severe type 1, and type 3 vWD patients is to
normalize vWF activities (vWF:RCo and vWF:CB) and FVIII:C preferentially by vWF/FVIII
concentrates containing the high vWF multimers and a high vWF:RCo/FVIII ratio to achieve
normal primary and secondary hemostasis. Based on the present study of a comparative
analysis of currently available vWF/FVIII concentrates, a classification of vWF/FVIII
products is proposed.
KEYWORDS
Hemostasis - von Willebrand disease (vWD) - von Willebrand factor (vWF) - factor VIII
- vWF multimers - ristocetin cofactor activity - collagen-binding activity - classification
of vWF products
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Ulrich BuddeM.D.
Coagulation Laboratory, Laboratory Association Prof. Arndt and Partners
Lademannbogen 61-63, D 22339 Hamburg, Germany
eMail: budde@labor-arndt-partner.de
