Consideration of platelet function disorders in patients with reduced VWF levels

Abstract

We read with interest the comprehensive National Heart, Lung, and Blood Institute (NHLBI) guidelines for the diagnosis and management of von Willebrand disease (VWD) [1]. However, we would like to draw attention to a practically important diagnostic issue that we frequently encounter in our clinical practice and that can mislead the unwary. The considerable overlap between von Willebrand factor (VWF) levels in patients with VWD and healthy controls is well established [2]. Although the authors acknowledge the potential difficulties in attributing bleeding symptoms to lowered VWF levels, particularly in cases with modest reductions in VWF levels, no mention is made of the possibility of co-existing bleeding disorders, including defects in platelet function and their consideration in the investigation of patients with possible VWD. The clinical manifestations of platelet function disorders and VWD are interchangeable [1,3], and it is our experience, as a tertiary referral centre, that abnormalities of platelet function are not infrequently found in patients with reduced or borderline levels of VWF. We have 25 patients registered at this centre with dual defects of various kinds, at least half of whom have a diagnosis of both VWD and a defect in platelet function. While the population frequency of platelet function disorders is unknown, as we have 208 patients registered with platelet function disorders and 566 with VWD, it is not surprising that the combination turns up. Failure to recognize this would lead to inappropriate treatment. We are planning to undertake a systematic survey of all our patients to establish the frequency of platelet function disorder in VWD at this tertiary centre. In view of the low specificity of the platelet function analyser (PFA-100) test reported in mild VWD phenotypes, the authors do not support the routine use of such primary haemostatic screening in the investigation of VWD. High false-negative rates on PFA-100 analysis have also been described in patients with platelet function defects [4–5]. Furthermore, measurement of the bleeding time is also known to lack specificity and sensitivity in the diagnosis of these patients. It is our practice to perform platelet aggregometry studies and quantify platelet nucleotides at an early stage in the investigation of patients with a history of mucocutaneous bleeding and patients with a diagnosis of VWD in the absence of significantly lowered VWF levels. While the use of optical platelet aggregometry is limited to specialist laboratories, the development of impedance aggregometers (multiplate analysis) may widen the availability of these studies, and their validation in the diagnosis of platelet function disorders is required. In summary, the early consideration of platelet function disorders when investigating patients for VWD reduces the frequency of incorrectly attributing bleeding symptoms to mild reductions in VWF levels resulting in improved clinical management and outcomes in these patients.