Abstract Number: PB0834
Meeting: ISTH 2022 Congress
Theme: Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies » VWF and von Willebrand Factor Disorders - Clinical Conditions
Background: Diagnostics of von Willebrand disease (VWD) is a complex process that aims to distinguish between qualitative and quantitative defects of von Willebrand factor (VWF) and reliably determine the subtype of VWD. In general, if all available VWF assays are used, genetic testing for screening mutations may only act to confirm a patient´s phenotype. But the identification of causal mutations may be crucial for effective patient diagnosis and may also provide a more specific diagnosis to aid appropriate management.
Aims: Report the own experience with diagnostics of two patients with the mixed VWD phenotype
Methods: The complete laboratory diagnostics of VWD was realised, routine coagulation testing,screening for VWD (VWF:Ac, VWF:Ag, FVIII:C, VWF:CBA) and discrimination tests (multimer analysis, genetic testing of the whole VWF gene)
Results: In the patients laboratory findings we observed proportionally reduced values of VWF:Ag and VWF:Ac, which does not indicate a dysfunctional VWF defect (V16: VWF:Ag = 0.25 IU/ml, VWF:Ac = 0.17 IU/ml, FVIII:C = 0,431 IU/ml, vWF:CBA = 0,11 IU/ml; V21: VWF:Ag = 0.13 IU/ml, VWF:Ac = 0.16 IU/ml, FVIII:C = 0,342 IU/ml, vWF:CBA = 0,034 IU/ml). However, multimer analysis revealed a deficiency of IMW and HMW multimers of VWF (V16: Low 12% (12-15%) Med 7% (22-35%) High 8% (47-70%); V21: Low 17,3% Med 1,1 % High 5,8 %). Genetic testing revealed a heterozygous missense mutation Trp1144Gly in exon 26 of VWF gene .
Conclusion(s): Mutations in exon 26 VWF in the D3 domain, such as Trp1144Gly, manifest as dominant type 1 VWD, but with abnormal multimers with typical 2A/IIE subtype features. The group of patients with similar mutations was designated as type 1/2E. Three studies demonstrated a significantly increased vWF:pp/vWF:Ag ratio in all 1/2E patients who carried Trp1144Gly mutation. This suggests a significant increase in the clearance of the vWF/FVIII complex.
This work was supported by grant VEGA 1/0187/17.
To cite this abstract in AMA style:
Zolkova J, Kolkova Z, Loderer D, Sokol J, Simurda T, Stryckova A, Dobrotova M, Ivankova J, Skornova I, Lasabova Z, Kubisz P, Stasko J. Mixed Phenotype 1/2E Von Willebrand Disease in Two Slovak Patients: Case Report [abstract]. https://abstracts.isth.org/abstract/mixed-phenotype-1-2e-von-willebrand-disease-in-two-slovak-patients-case-report/. Accessed March 21, 2024.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/mixed-phenotype-1-2e-von-willebrand-disease-in-two-slovak-patients-case-report/