Abstract | 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 GPIb 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.
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Authors | F Stufano, L Baronciani, M T Pagliari, F Franchi, G Cozzi, I Garcia-Oya, P Bucciarelli, M Boscarino, F Peyvandi |
Journal | Journal of thrombosis and haemostasis : JTH
(J Thromb Haemost)
Vol. 13
Issue 10
Pg. 1806-14
(Oct 2015)
ISSN: 1538-7836 [Electronic] England |
PMID | 26206100
(Publication Type: Comparative Study, Evaluation Study, Journal Article)
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Copyright | © 2015 International Society on Thrombosis and Haemostasis. |
Chemical References |
- Biomarkers
- Platelet Glycoprotein GPIb-IX Complex
- adhesion receptor
- von Willebrand Factor
- Ristocetin
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Topics |
- Biomarkers
(blood)
- Blood Platelets
(metabolism)
- Case-Control Studies
- Diagnosis, Differential
- Humans
- Mutation
- Platelet Aggregation
- Platelet Function Tests
- Platelet Glycoprotein GPIb-IX Complex
(genetics, metabolism)
- Predictive Value of Tests
- Protein Multimerization
- Ristocetin
(administration & dosage)
- Severity of Illness Index
- von Willebrand Disease, Type 2
(blood, diagnosis, genetics)
- von Willebrand Factor
(metabolism)
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