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Evaluation of an heterogeneous group of patients with von Willebrand disease using an assay alternative to ristocetin induced platelet agglutination
Author(s) -
Stufano F.,
Baronciani L.,
Pagliari M. T.,
Franchi F.,
Cozzi G.,
GarciaOya I.,
Bucciarelli P.,
Boscarino M.,
Peyvandi F.
Publication year - 2015
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.13062
Subject(s) - von willebrand factor , von willebrand disease , ristocetin , platelet , agglutination (biology) , population , medicine , antigen , chemistry , immunology , endocrinology , microbiology and biotechnology , biology , environmental health
Summary Background Diagnosis of von Willebrand disease ( VWD ) type 2 usually relies on the discrepancy between the von Willebrand factor ( VWF ) ristocetin cofactor activity (VWF:RCo) and VWF antigen (VWF:Ag). Type 2B patients can be discriminated from other qualitative VWD variants by using ristocetin‐induced platelet agglutination ( RIPA ) test. The major limitation of RIPA is the requirement of fresh blood sample. Objectives In this study, we evaluated the VWF gain‐of‐function mutant GPI b binding (VWF:GPIbM) and VWF:RCo assays to investigate whether the VWF:GPIbM/VWF:RCo ratio was able to identify the type 2B variant among an heterogeneous VWD population, previously characterized following the ISTH ‐ SSC guidelines. Patients/methods Seventy‐six VWD patients and 31 healthy subjects were evaluated by using VWF:Ag, VWF:RCo, and VWF:GPIbM assays. Results The mean (minimum–maximum values) VWF:GPIbM/VWF:RCo ratio was higher in type 2B patients (2.53, 0.84–6.11) than in healthy controls (1.05, 0.87–1.34), type 1 (0.85, 0.51–1.15), 2A (1.20, 0.36–2.82), and 2M (1.07, 0.91–1.38) ( P < 0.0001). Type 2B variants were divided into four groups (A, B, C, and D) according to their different multimeric patterns. The mean value of the VWF:GPIbM/VWF:RCo ratio in the four groups showed an increasing trend from group A (1.08) to D (3.69), proportional to the loss of high molecular weight multimers. Among 32 type 2B patients, previously diagnosed with RIPA , 8 (mainly with a type I New York/Malmö phenotype) were not confirmed using the VWF:GPIbM/VWF:RCo ratio. Conclusions Whenever the RIPA test is not feasible, the VWF:GPIbM/VWF:RCo ratio might help to identify severe type 2B VWD patients.