PB0356 - Acquired von Willebrand syndrome secondary to monoclonal gammopathy: a single center case series.

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Quentin Van Thillo

Resident
Department of Haematology, University Hospitals Leuven, Leuven, Belgium
Leuven, Vlaams-Brabant, Belgium

Co-Author(s)

JB

Jan Brijs

Resident
Department of Haematology, University Hospitals Leuven, Leuven, Belgium
Leuven, Vlaams-Brabant, Belgium
FS

Finn Segers

PhD student
Lab for Experimental Hematology KU Leuven, Leuven, Belgium
Leuven, Vlaams-Brabant, Belgium
UD

Ulrike Douven

Staff member
Ziekenhuis Geel, Geel, Belgium
Geel, Antwerpen, Belgium
MD

Michel Delforge

Professor
Department of Haematology, University Hospitals Leuven, Leuven, Belgium
Leuven, Vlaams-Brabant, Belgium
AJ

Ann Janssens

Professor
Department of Haematology, University Hospitals Leuven, Leuven, Belgium
Leuven, Vlaams-Brabant, Belgium
Thomas Vanassche

Professor
Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium
Leuven, Vlaams-Brabant, Belgium
Peter Verhamme, MD PhD

Professor
Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium
Leuven, Vlaams-Brabant, Belgium

Background: Acquired von Willebrand syndrome (AvWS) is a rare bleeding disorder with a similar bleeding phenotype to congenital von Willebrand disease (vWD). AvWS can arise in patients with monoclonal gammopathy. Management of the bleeding phenotype in this subset of patients can be particularly challenging (Franchini 2020). To this day, clear recommendations on how to handle AvWS secondary to monoclonal gammopathy are lacking.

Aims: Our aim was to characterize the clinical and laboratory findings in AvWS secondary to monoclonal gammopathy at our center.

Methods: We retrospectively analyzed the data of adult patients who were diagnosed at University Hospitals Leuven, Belgium between 2002 and 2023. All laboratory analyses were performed following routine clinical practice.

Results: Seven patients with a monoclonal gammopathy were diagnosed with AvWS (Table 1). Most patients had a monoclonal gammopathy of unknown significance (MGUS) according to IMWG at diagnosis (n = 6) with either monoclonal IgG (n = 5) or IgM (n = 1). One patient had a Waldenström macroglobulinemia (WM) at diagnosis. Two patients progressed to smoldering myeloma and multiple myeloma (MM), respectively. Patients with IgG MGUS generally responded well to intravenous immunoglobulins (IVIG) (Figure 1). Notably, one patient who did not respond, also had heterozygous mutations in the von Willebrand factor (VWF) and fibrinogen gamma chain (FGG) genes. The IgM patients were treated with either vWF/FVIII concentrate alone, or a combination of vWF/FVIII concentrate, rituximab and methylprednisolone due to a lack of clinical benefit of IVIG. The patients with WM and MM were treated accordingly.

Conclusion(s): Hematologists should think of the association between monoclonal gammopathy and AvWS. As suggested in the literature (Federici 1998), we confirm the effect of IVIG in IgG-associated AvWS. In case of poor response, sequencing of the VWF gene might be insightful. For IgM-associated AvWS, we observed better results administering vWF/FVIII concentrate or a combination of therapies.