Von Willebrand factor propeptide and pathophysiological mechanisms in European and Iranian patients with type 3 von Willebrand disease enrolled in the 3WINTERS‐IPS study
Year: 2022
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Type 3 von Willebrand disease (VWD) is a severe bleeding disorder caused by the virtually complete absence of von Willebrand factor (VWF). Pathophysiological mechanisms of VWD like defective synthesis, secretion, and clearance of VWF have previously been evaluated using ratios of VWF propeptide (VWFpp) over VWF antigen (VWF:Ag) and factor (F)VIII coagulant activity (FVIII:C) over VWF:Ag. OBJECTIVE: To investigate whether the VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios may also be applied to understand the pathophysiological mechanism underlying type 3 VWD and whether VWFpp is associated with bleeding severity. METHODS: European and Iranian type 3 patients were enrolled in the 3WINTERS-IPS study. Plasma samples and buffy coats were collected and a bleeding assessment tool was administered at enrolment. VWF:Ag, VWFpp, FVIII:C, and genetic analyses were performed centrally, to confirm patients' diagnoses. VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios were compared among different variant classes using the Mann-Whitney test. Median differences with 95% confidence intervals (CI) were estimated using the Hodges-Lehmann method. VWFpp association with bleeding symptoms was assessed using Spearman's rank correlation. RESULTS: Homozygosity/compound heterozygosity for missense variants showed higher VWFpp level and VWFpp/VWF:Ag ratio than homozygosity/compound heterozygosity for null variants ([VWFpp median difference, 1.4 IU/dl; 95% CI, 0.2-2.7; P = .016]; [VWFpp/VWF:Ag median difference, 1.4; 95% CI, 0-4.2; P = .054]). FVIII: C/VWF:Ag ratio was similarly increased in both. VWFpp level did not correlate with the bleeding symptoms (r = .024; P = .778). CONCLUSIONS: An increased VWFpp/VWF:Ag ratio is indicative of missense variants, whereas FVIII:C/VWF:Ag ratio does not discriminate missense from null alleles. The VWFpp level was not associated with the severity of bleeding phenotype.
DOI: 10.1111/jth.15658
Authors: Maria Teresa Pagliari, Frits R. Rosendaal, Minoo Ahmadinejad, Zahra Badiee, Mohammad‐Reza Baghaipour, Luciano Baronciani, Olga Benítez Hidalgo, Imre Bodó, Ulrich Budde, Giancarlo Castaman, Peyman Eshghi, Jenny Goudemand, Mehran Karimi, Bijan Keikhaei, Riitta Lassila, Frank W.G. Leebeek, Maria Fernanda Lopez Fernandez, Pier Mannuccio Mannucci, Renato Marino, Johannes Oldenburg, Ian Peake, Cristina Santoro, Reinhard Schneppenheim, Andreas Tiede, Gholamreza Toogeh, Alberto Tosetto, Marc Trossaert, Hamideh Yadegari, Eva M.K. Zetterberg, Flora Peyvandi, Augusto B. Federici, Jeroen Eikenboom
Institutions: University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Leiden University Medical Center, High Institute for Education and Research in Transfusion Medicine, Shahid Beheshti University of Medical Sciences, Mashhad University of Medical Sciences, Hemophilia Center of Iran, Vall d'Hebron Hospital Universitari, Semmelweis University, Azienda Ospedaliero-Universitaria Careggi, Université de Lille, Centre Hospitalier Universitaire de Lille, Shiraz University, Shiraz University of Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, University of Helsinki, Helsinki University Hospital, Erasmus MC, Complexo Hospitalario Universitario A Coruña, Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari, University of Bonn, University of Sheffield, Policlinico Umberto I, University Medical Center Hamburg-Eppendorf, Medizinische Hochschule Hannover, Tehran University of Medical Sciences, Ospedale San Bortolo, Skåne University Hospital, Luigi Sacco Hospital
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,500
Award: G5165200114
OpenAlex ID: W4210693078