The elusive and heterogeneous pattern of type 2M von Willebrand disease: A diagnostic challenge. (19th September 2018)

• Record Type: Journal Article
• Authors: Casonato, Alessandra; Galletta, Eva; Daidone, Viviana
• Is Part Of: European journal of haematology. Volume 101:Number 5(2018)
• Page Start: 684
• Page End: 690
• Publication Date: 2018-09-19
• Subjects: type 2M VWD -- von Willebrand disease -- von Willebrand factor -- VWD diagnosis -- VWF:RCo; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; Blood -- Periodicals; 616.15005
• DOI: 10.1111/ejh.13159
• Languages: English
• ISSNs: 0902-4441

Abstract

Abstract: 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.