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The elusive and heterogeneous pattern of type 2M von Willebrand disease: A diagnostic challenge
Author(s) -
Casonato Alessandra,
Galletta Eva,
Daidone Viviana
Publication year - 2018
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.13159
Subject(s) - von willebrand disease , von willebrand factor , ristocetin , platelet , chemistry , medicine , endocrinology , hemostasis , antigen , immunology
Type 2M is a very heterogeneous form of von Willebrand disease (VWD) associated with impaired platelet and von Willebrand factor (VWF) interactions not due to a lack of large VWF multimers. Objectives To investigate type 2M heterogeneity and to establish the most appropriate diagnostic flowchart. Methods Hemostatic and genetic VWF analyses were performed in 14 type 2M VWD patients carrying the p.G1324S, p.R1374H, p.R1374C, p.A1344_A1350del, or p.F1293L mutations. Results PFA‐100 was always significantly prolonged, and ristocetin‐induced platelet aggregation (RIPA) and VWF ristocetin cofactor (VWF:RCo) greatly reduced or absent. Plasma VWF antigen (VWF:Ag) was reduced except in the p.G1324S patient, while platelet VWF:Ag was normal or near normal except in the p.R1374C patients. The ratio of collagen binding (VWF:CB) to VWF:Ag was normal or near normal except in patients carrying the p.R1374H and p.A1344_A1350del mutations, whose large VWF multimers were slightly reduced. Multimer patterns were normal or lacking in large oligomers, or with larger than normal VWF components. Conclusions Only PFA100, RIPA and VWF:RCo were always abnormal. We thus propose a minimal diagnostic test battery: RIPA (demonstrating the defective VWF‐platelet interaction), VWF:Ag (exploring VWF synthesis), and VWF:CB and its ratio (to explore multimer patterns). Other tests would only serve for confirmation, if necessary.