Abstract Number: PB1576
Meeting: ISTH 2020 Congress
Theme: Platelet Disorders and von Willebrand Disease » VWF and von Willebrand Factor Disorders - Clinical Conditions
Background: Type 3 von Willebrand disease (VWD) is the most severe form of VWD but fortunately the less frequent (< 5% of cases). It's an autosomal recessive disease, characterized by a near-total absence of von Willebrand factor (VWF) antigen and activity, a secondary factor VIII (FVIII) deficiency and bleeding symptoms. Replacement therapy is the main treatment but there is around 10% risk of developing an alloantibody against VWF, rendering the treatment ineffective.
Aims: To identify VWF variants that could be associated to a higher risk to develop alloantibodies.
Methods: We studied the database from the French Reference Center for VWD to identify patients that developed an alloantibody and had the same pathogenic variant in VWF.
Results: Among the 6 patients with type 3 VWD who developed anti-VWF alloantibodies, 3 had the same homozygous variant c.3931C>T, p.Gln1311* in exon 28. A prophylaxis treatment has been initiated with plasma-derived VWF and FVIII (Wilfactin® ± Factane®) for all patients after their diagnosis of type 3 VWD because of severe bleeding symptoms (ISTH-BAT score: 14-24). The 3 patients developed an anti-VWF alloantibody. One of the patient also has mild haemophilia A (c.2113+466_2113+473del in intron 13) leading to an undetectable FVIII level (FVIII:C < 1%) in combination with his type 3 VWD. He developed an additional anti-FVIII alloantibody. In the literature, the homozygous p.Gln1311* variant has been described in Spain, Portugal and Iran in 17 type 3 VWD patients in total. An anti-VWF alloantibody was described for 1 on 5 patients identified in Portugal. A founder effect was hypothesized with a gypsy origin in Spain, that could be the same origin for 2 of our patients.
Conclusions: We identified the p.Gln1311* variant as a type 3 VWD variant associated with a high risk of allo-immunisation. This information must be considered for future patients in the discussion of prophylaxis instauration.
To cite this abstract in AMA style:
Lassalle F, Zawadzki C, Boisseau P, Jeanpierre E, Rauch A, Paris C, Hochart A, Repesse Y, Veyradier A, Harroche A, Biron-Andréani C, Falaise C, Goudemand J, Susen S. The Homozygous Variant p.Gln1311* in Exon 28 of VWF Is Causing Type 3 von Willebrand Disease and Is at High Risk of Allo-Immunisation [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/the-homozygous-variant-p-gln1311-in-exon-28-of-vwf-is-causing-type-3-von-willebrand-disease-and-is-at-high-risk-of-allo-immunisation/. Accessed October 1, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/the-homozygous-variant-p-gln1311-in-exon-28-of-vwf-is-causing-type-3-von-willebrand-disease-and-is-at-high-risk-of-allo-immunisation/