Risk of excessive bleeding associated with marginally low von Willebrand factor and mild platelet dysfunction

Bleeding symptoms are so commonly reported that it is not known whether they associate causally or coincidentally with mild but measurable primary hemostatic defects. OBJECTIVES/PATIENTS/METHODS: In order to evaluate if the mild primary hemostatic defects are truly causative of increased bleeding symptoms, we surveyed a population of healthy teenagers for bleeding symptoms. Using a case-control approach, we then estimated the risk of excessive bleeding associated with low von Willebrand factor (defined as VWF below the 5th percentile of a normal reference population), and with mild platelet dysfunction [PD, defined as concurrent reduced platelet aggregation responses to two agonists (adenosine diphosphate and epinephrine)].

Excessive bleeding was present in 63 out of 809 teenagers (7.8%). Among the 49 cases who were tested for VWF, low values by three measures were more commonly present than in 166 controls, specifically, ristocetin cofactor (RCo) activity [20.4% vs. 5.4%, odds ratio (OR) 4.5], collagen binding (14.3% vs. 4.2%, OR 3.8), and antigen level (20.4% vs. 6.0%, OR 4.0). The low RCo values ranged from 35 to 45 U dL(-1) except for a single case with 26 U dL(-1). Of the 47 teenagers with excessive bleeding who underwent platelet aggregation studies, reduced responses were more common than in controls (12.8% vs. 4.4%, OR 3.2). Twenty-nine per cent of cases with excessive bleeding had either low RCo or PD.

Almost one in three teenagers who report excessive bleeding is likely to have a measurable hemostatic disturbance manifested either by marginally low VWF (by three measures) or by mild PD.