Clinical and laboratory presentation and underlying mechanism in patients with low VWF

Authors: Seidizadeh, O; Ciavarella, A; Baronciani, L; Boggio, F; Ballardini, F; Cozzi, G; Colpani, P; Pagliari, MT; Novembrino, C; Siboni, SM; Peyvandi, F

Affiliations: University of Milan, Milano, Italy. Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, A.Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy. Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS CA’ GRANDA Maggiore Policlinico Hospital Fondation, Milan, Italy. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy. Department of Oncology and Onco-Hematology, University of Milan, Milano, Italy. Maggiore Policlinico and Luigi Villa Foundation, Milan, Italy. Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, and Fondazione Luigi Villa, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy. Laboratory of Clinical Chemistry and Microbiology and Angelo Bianchi Bonomi Haemophilia and Thrombosis Center, Milan, Italy, Università degli Studi di Milano, Milan, Italy., Milan, Italy. Medicina Generale Emostasi e Trombosi Angelo Bianchi Bonomi Hemophilia and Thrombosis Cente.

Publication: Thromb Haemost. 0340-6245. 2023

ABSTRACT: Low von Willebrand factor (VWF) refers to subjects with plasma levels of 30-50 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. We included 250 patients characterized with low VWF. The 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 to those of 120 healthy controls. Cases with abnormal screening tests were further evaluated for coagulation factor levels and platelet disorders. 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. 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.