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Thromb Haemost 2024; 124(04): 340-350
DOI: 10.1055/a-2186-6362
Coagulation and Fibrinolysis

Clinical and Laboratory Presentation and Underlying Mechanism in Patients with Low VWF

Omid Seidizadeh 
1   Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
,
Alessandro Ciavarella
1   Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
,
Luciano Baronciani
2   Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
,
Federico Boggio
1   Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
,
Francesco Ballardini
3   Department of Oncology and Onco-Hematology, University of Milan, Milan, Italy
,
Giovanna Cozzi
2   Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
,
Paola Colpani
2   Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
,
Maria Teresa Pagliari
2   Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
,
Cristina Novembrino
2   Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
,
Simona Maria Siboni
2   Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
,
Flora Peyvandi
1   Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
2   Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
› Author Affiliations Funding This work was partially supported by the Italian Ministry of Health-Bando Ricerca Corrente.
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Abstract

Background Low von Willebrand factor (VWF) refers to subjects with plasma levels of 30 to 50 IU/dL. The mechanism of low VWF is poorly understood. We chose to determine the clinical presentation, laboratory phenotype, and underlying mechanisms of low VWF.

Material and Methods We included 250 patients characterized with low VWF. The International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) was used to assess clinical symptoms. To determine the underlying mechanisms of low VWF, we used as markers the VWF propeptide (VWFpp) assay and FVIII:C/VWF:Ag ratio for VWF synthesis and the VWFpp/VWF:Ag ratio for VWF clearance. Results were compared with those of 120 healthy controls. Cases with abnormal screening tests were further evaluated for coagulation factor levels and platelet disorders.

Results The median age of the cohort was 35 years (range 3–85), 21% were children (n = 53), 34% were adult males (n = 85), and 45% (n = 112) were adult females. According to the ISTH-BAT, abnormal bleeding was found in 35% of children, 47% of males, and 49% of females. No association was found between VWF activity levels and ISTH-BAT. Patients showed an overall decreased VWF synthesis/secretion and an enhanced VWF clearance was identified in 33% of them. In 89 patients (36%), there were other hemostasis-related defects, but there was no difference in the ISTH-BAT between the two groups.

Conclusion Our findings indicate that reduced VWF synthesis/secretion and enhanced VWF clearance are major mechanisms of low VWF levels. Patients with low VWF have significant bleeding manifestations. While other hemostasis defects occurred together with low VWF, this combination did not exacerbate clinical symptoms.

Keywords

VWD - VWF - low VWF - ISTH-BAT

Data Availability Statement

Contact the corresponding author for other data sharing: flora.peyvandi@unimi.it.


Authors' Contribution

O.S. and F.P. conceptualized the study. O.S. collected and analyzed data and wrote the manuscript. P.C., G.C., M.T.P., and C.N. performed the phenotypic tests; S.M.S., A.C., F.B., and F.P. were involved in the patient's evaluation. L.B. and F.P. critically revised the manuscript. All authors have approved the final manuscript.




Publication History

Received: 14 July 2023

Accepted: 04 October 2023

Accepted Manuscript online:
05 October 2023

Article published online:
02 November 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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