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Coagulation Disorders von Willebrand Disease
Long-term Prophylaxis in von Willebrand Disease –
How Should It Be Given and for Whom?
a report by
Erik Berntorp, Sharyne M Donfield and Thomas C Abshire
The von Willebrand Disease Prophylaxis (VIP) Study Group
Von Willebrand disease (VWD) is a common hereditary bleeding (28.7%) than in North America (12.2%; p=0.0004). The use of
disorder that may affect as many as 1% of the general population.
1
prophylaxis for patients with type 1 and type 2 VWD was rare in both
VWD is classified into three major categories based on the type of regions.
10
The most commonly cited reasons for initiating prophylaxis
defect and degree of deficiency of von Willebrand factor (VWF). Type were joint (40%), epistaxis/oral (23%) and GI bleeding (14%) and
1 is the most common, affecting approximately 75% of those who are menorrhagia (5%).
symptomatic with VWD,
2
with type 2 making up most of the
The rationale for initiating long-term prophylaxis in VWD is that it has
been successfully used in severe haemophilia, showing that it is feasible
to implement early in life in a home setting and that prevention of
Von Willebrand disease is a common
bleeding and its consequences is possible.
11,12
Since joint haemorrhages
hereditary bleeding disorder that
with development of arthropathy can occur, particularly in type 3 VWD,
and frequent mucous membrane bleeds, GI bleeding and menorrhagia
may affect as many as 1% of the
can jeopardise quality of life or even be life-threatening, it is logical to
general population.
consider application of the experience learned in haemophilia to VWD.
Data to support this come from a multicentre study conducted in Sweden
in a group of 52 subjects with VWF ristocetin co-factor (VWF:RCo) <8%
and coagulation factor VIII:C (FVIII:C) <10%.
13
Thirty-nine were on long-
remainder. Type 3, the most severe form of VWD, is rare, and is term prophylaxis and 13 were treated on demand. The study showed that
estimated to affect from 0.1 to 5.3 per million population.
3
Data those beginning prophylaxis below five years of age had few or no
summarised from six studies showed that among referred patients, bleeding episodes, and none had clinical signs of arthropathy or reported
type 1 accounted for approximately 70% of VWD cases, type 2 about joint bleeding. Subjects beginning prophylaxis above 15 years of age
17% and type 3 about 13%.
3
An extensive survey among haemophilia usually reported a substantial reduction in joint bleeding, but had clinical
centres in Italy reported frequencies of 73, 21 and 6 for VWD types and radiological signs of joint disease. Reductions in other types of
1, 2 and 3, respectively.
4
However, estimation of prevalence and bleeding, including epistaxis, were demonstrated. The investigators
classification of type is complicated by a number of clinical and concluded that long-term prophylactic treatment in VWD is warranted in
laboratory factors. the majority of cases with type 3 disease and sometimes, depending on
the clinical phenotype, for those with other types.
Clinically, the leading symptoms in VWD are bleeding, chiefly of the
mucosal type (e.g. epistaxis, gingival or gastrointestinal [GI] bleeding) and The VWD Prophylaxis Network (VWD PN) was formed to investigate the
menorrhagia. In severe forms of VWD with secondary deficiency of factor role of prophylaxis in clinically severe VWD that is non-responsive to other
VIII, spontaneous joint and muscular bleeding resembling that observed in treatments. The VWD International Prophylaxis (VIP) study is an initiative
severe haemophilia A may also be observed. of the VWD PN. The primary objectives of the VIP study are to:
Strategies for treatment vary by type and severity, and include the use of • study the effect of prophylaxis on bleeding frequency; and
1-desamino-8-D-arginine vasopressin (DDAVP), antifibrinolytics and • establish optimal treatment regimens for joint bleeding, GI bleeding,
replacement therapy. Type 1 VWD is the most responsive to DDAVP, type epistaxis and menorrhagia.
2 is generally poorly responsive and type 3 is almost invariably
unresponsive.
5–8
VWF replacement therapy is indicated for the treatment The secondary objectives are to:
of type 3 and for those with types 1 and 2 who do not respond to
DDAVP. Antifibrinolytic agents can be used as adjuncts to DDAVP or • determine how quality of life at baseline is related to bleeding history
VWF concentrates.
9
and whether changes in bleeding frequency are associated with
changes in quality of life among patients with VWD on prophylaxis;
Investigators participating in a survey of 74 treatment centres conducted • identify the frequency of development of inhibitory antibodies to VWF
between 2005 and 2006 reported that approximately 70% of their among patients with VWD on prophylaxis;
patients with type 3 VWD had been treated with VWF-containing • study the frequency and indications for hospitalisations among
plasma-derived products in the previous 12 months. Twenty-two per patients with VWD on prophylaxis; and
cent were on prophylaxis, but this occurred more commonly in Europe • evaluate the safety of prophylaxis among patients with VWD.
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