TY - JOUR
T1 - Genetic variants, thrombocytopenia, and clinical phenotype of type 2B von Willebrand disease
T2 - a median 16-year follow-up study
AU - WiN study group
AU - van Kwawegen, C. B.
AU - Atiq, F.
AU - Endenburg, Dara
AU - Fijnvandraat, Karin
AU - van Galen, Karin P.M.
AU - Cnossen, Marjon H.
AU - Schols, S. E.M.
AU - Kruip, Marieke J.H.A.
AU - van Heerde, Waander L.
AU - de Meris, Joke
AU - van der Bom, Johanna G.
AU - Eikenboom, Jeroen
AU - Meijer, Karina
AU - Leebeek, Frank W.G.
AU - Fijnvandraat, K.
AU - Coppens, M.
AU - Zweegman, S.
AU - de Meris, J.
AU - Goverde, G. J.
AU - Dors, N.
AU - Nijziel, M. R.
AU - Nieuwenhuizen, L.
AU - Tamminga, R. Y.J.
AU - Ypma, P. F.
AU - Eikenboom, H. C.J.
AU - van der Bom, J. G.
AU - Smiers, F. J.W.
AU - Granzen, B.
AU - Hamulyák, K.
AU - Brons, P.
AU - Laros-van Gorkom, B. A.P.
AU - Schols, S. E.M.
AU - Leebeek, F. W.G.
AU - Boender, J.
AU - Atiq, F.
AU - Mauser-Bunschoten, E. P.
AU - van Galen, K. P.M.
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/12
Y1 - 2024/12
N2 - Background: Type 2B von Willebrand disease (VWD) is a bleeding disorder caused by gain-of-function variants in the VWF gene. The laboratory and clinical phenotype of type 2B VWD is heterogeneous.Objectives: We investigated associations between genotype and phenotype over a median of 16 years follow-up in a large cohort of well-characterized patients.Methods: We included 64 genetically confirmed type 2B VWD patients from the national multicenter “Willebrand in the Netherlands” study and retrospectively collected clinical and laboratory data from electronic patient records. We analyzed associations between genotype and thrombocytopenia, bleeding phenotype, and events leading to endothelial activation and von Willebrand factor (VWF) secretion, including surgery, desmopressin administration, pregnancy, and delivery.Results: Thrombocytopenia manifested in 67.2% of patients, with varying occurrences between genetic variants (p.Arg1306Trp: 75.0%, p.Arg1308Cys: 58.3%). The most important determinant of thrombocytopenia was the p.Arg1306Trp VWF variant (odds ratio, 25.1). Platelet counts strongly varied over time and were continuously <150 × 109/L in 37.5% of patients with p.Arg1306Trp vs 8.3% in p.Arg1308Cys. In our analysis, endothelial activation was not an independent determinant (odds ratio, 1.3) for thrombocytopenia occurrence. No association was found between thrombocytopenia and cumulative bleeding scores or annual bleeding rates. Four women showed declining platelet counts in all full-term pregnancies (n = 8) during the third trimester with a sharp decrease in the week before delivery. Postpartum hemorrhage, defined as >500 mL estimated blood loss at delivery, occurred in 5 of 8 deliveries, despite prophylactic treatment with VWF concentrates.Conclusion: This study reveals a strong association between VWF variant p.Arg1306Trp and thrombocytopenia in type 2B VWD patients.
AB - Background: Type 2B von Willebrand disease (VWD) is a bleeding disorder caused by gain-of-function variants in the VWF gene. The laboratory and clinical phenotype of type 2B VWD is heterogeneous.Objectives: We investigated associations between genotype and phenotype over a median of 16 years follow-up in a large cohort of well-characterized patients.Methods: We included 64 genetically confirmed type 2B VWD patients from the national multicenter “Willebrand in the Netherlands” study and retrospectively collected clinical and laboratory data from electronic patient records. We analyzed associations between genotype and thrombocytopenia, bleeding phenotype, and events leading to endothelial activation and von Willebrand factor (VWF) secretion, including surgery, desmopressin administration, pregnancy, and delivery.Results: Thrombocytopenia manifested in 67.2% of patients, with varying occurrences between genetic variants (p.Arg1306Trp: 75.0%, p.Arg1308Cys: 58.3%). The most important determinant of thrombocytopenia was the p.Arg1306Trp VWF variant (odds ratio, 25.1). Platelet counts strongly varied over time and were continuously <150 × 109/L in 37.5% of patients with p.Arg1306Trp vs 8.3% in p.Arg1308Cys. In our analysis, endothelial activation was not an independent determinant (odds ratio, 1.3) for thrombocytopenia occurrence. No association was found between thrombocytopenia and cumulative bleeding scores or annual bleeding rates. Four women showed declining platelet counts in all full-term pregnancies (n = 8) during the third trimester with a sharp decrease in the week before delivery. Postpartum hemorrhage, defined as >500 mL estimated blood loss at delivery, occurred in 5 of 8 deliveries, despite prophylactic treatment with VWF concentrates.Conclusion: This study reveals a strong association between VWF variant p.Arg1306Trp and thrombocytopenia in type 2B VWD patients.
KW - desmopressin
KW - genotype
KW - pregnancy
KW - thrombocytopenia
KW - von Willebrand disease
UR - http://www.scopus.com/inward/record.url?scp=85206930096&partnerID=8YFLogxK
U2 - 10.1016/j.jtha.2024.08.028
DO - 10.1016/j.jtha.2024.08.028
M3 - Article
C2 - 39343102
AN - SCOPUS:85206930096
SN - 1538-7933
VL - 22
SP - 3460
EP - 3472
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
IS - 12
ER -