Abstract Number: OC 13.3
Meeting: ISTH 2021 Congress
Background: Von Willebrand disease (vWD) is an inherited bleeding disorder that is caused by a defect of von Willebrand factor (vWF). vWD has three subtypes. All these subtypes are classified on the basis of vWF antigen, Ricof and some other factors. Type III vWD is classified as having vWF antigen level less than 3 IU/DL. Even in type III vWD severity of the disease vary from patient to patient. The severity of bleeding can be assessed by different bleeding assessment tools including Condensed MCMDM1 tool.
Aims: To assess the association of genetic alterations with the severity of disease in type III vWD.
Methods: A total of 70 confirmed patients of type III vWD were enrolled in the study. After informed conset, all these patients were categorized as having severe (bleeding score less then 13) and very severe disease (bleeding score 13 or more) measured by the Condensed MCMDM1 questionnaire. Mutational analysis was performed by Next generation sequencing on ion torrent PGM platform using Thermo Fischer kits and consumables. All the mutations were confirmed by sanger sequencing.
Results: Next-Generation Sequencing revealed pathogenic mutations in 78% of the patients of vWD (Type III). Stop codon mutations were present in 44.9% cases, frameshift mutations in 22.24%, missense mutations in 32.6% and splice site mutations in 10.2% cases. Homozygous mutations were seen in 91.8% of the patients exhibiting pathogenic mutations while compound heterozygosity was seen in 4.08% and Heterozygous mutations were seen 4.08% . A total of 19 mutations were identified in all the patients. Among them, 5 are novel mutations. Stop codon mutations are associated with very severe bleeding phenotype with p-value of <0.01 while other mutations have relatively less severity.
Conclusions: Very severe form of type III vWD is associated with stop codons. A total of 22% patients still need work up to delineate pathogenic mutation/s.
To cite this abstract in AMA style:Naveed MA, Khaliq S, Mohsin S, Abid A, Saleem U, Ammar A. Association of Genetic Alterations with Severity of Disease in Type III vWD Patients [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/association-of-genetic-alterations-with-severity-of-disease-in-type-iii-vwd-patients/. Accessed October 2, 2023.
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