ABSTRACT
The current standard for the diagnosis and management of patients with congenital
von Willebrand disease (vWD) includes bleeding times (BTs), PFA-100 closure time (PFA-CT),
factor (F) VIII:coagulant activity (C), vWF:antigen (Ag), vWF:ristocetin cofactor
activity (RCo), a sensitive vWF:collagen-binding activity (CB), ristocetin-induced
platelet aggregation (RIPA), analysis of vWF multimers in low- and high-resolution
agarose gels, and the response to desmopressin. Guidelines and recommendations for
prophylaxis and treatment of bleedings in vWD patients with vWF/FVIII concentrates
should be derived from analysis of the content of these concentrates and from pharmacokinetic
studies in different types of vWD patients with severe type 1, 2, or 3 vWD. The vWF/FVIII
concentrates should be characterized by labeling with FVIII:C, vWF:RCo, vWF:CB, and
vWF multimeric pattern, which will determine their predicted efficacy and safety in
prospective management studies. Because the bleeding tendency is moderate in type
2 and severe in type 3 vWD, and because the FVIII:C levels are subnormal in type 2
and very low in type 3 vWD patients, new guidelines using vWF:RCo unit dosing for
the prophylaxis and treatment of bleeding episodes are proposed. Such guidelines should
be stratified for the severity of bleeding, the type of surgery (either minor or major),
and also for the severity and type of vWD (i.e., either type 2 or 3 vWD).
KEYWORDS
Von Willebrand factor - von Willebrand disease - ristocetin cofactor activity - von
Willebrand collagen-binding activity - bleeding time - desmopressin (DDAVP) - von
Willebrand factor concentrates
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Jan Jacques MichielsM.D. Ph.D.
Goodheart Institute, Hemostasis Thrombosis Science Center, Erasmus Tower
Veenmos 13, 3069 AT Rotterdam, The Netherlands
Email: postbus@goodheartcenter.demon.nl