The Von Willebrand Disease (VWD) International Prophylaxis Study

The most common indications for vWD prophylaxis included joint bleeding, epistaxis,
gastrointestinal (GI) bleeding, and menorrhagia. Thus, an effort to establish optimal
treatment regimens for these indications, through a period of prospective evaluation, is the
primary focus of this research. Other goals include a retrospective study of the effect of
prophylaxis on bleeding frequency, and a retrospective natural history study of GI bleeding
in VWD.

Inclusion Criteria:

Type 1: eligible for participation if

- ≤20% RCo and/or ≤20% FVIII; and

- DDAVP non-responsive, defined as occurrence of bleeding episodes not responding
satisfactorily to desmopressin, or deemed non-responsive a priori by the investigator;
and

- Bleeding indication criteria are met

Type 2: eligible for participation if

- DDAVP non-responsive, defined as occurrence of bleeding episodes not responding
satisfactorily to desmopressin, or deemed non-responsive a priori by the investigator;
or Type 2B;

- Bleeding indication criteria are met

Type 3: eligible for participation if

- Bleeding indication criteria are met

Bleeding Indication Criteria:

- Joint Bleeding: documentation of at least two apparently spontaneous bleeding episodes
in the same joint in the six months prior to enrollment; or three or more apparently
spontaneous bleeding episodes in different joints in the six months prior to
enrollment.

- GI Bleeding: history of two or more severe GI bleeding episodes associated with either
a drop in hemoglobin of ≥ 2 g/dl or requiring red blood cell transfusion or treatment
with VWD concentrate.

- Failure to identify other causes of bleeding.

- Menorrhagia: a diagnosis of menorrhagia; prospectively completed Pictorial Blood
Assessment Chart score >185 or required treatment with a VWD product for menstrual
bleeding on one or more occasions in the year prior to enrollment.

- Normal cervical cytology (PAP) within the six months prior to enrollment for females ≥
18 years of age.

- Epistaxis 1. Three or more bleeding episodes in a six-month period that required
treatment with VWD concentrates or red cell transfusions.