PB0289 - Significance of Parents’ evaluation in cases of Von Willebrand Disease

Background: Von Willebrand disease (VWD) is the most diagnosed autosomal inherited bleeding disorder. VWD types 1, 2A, 2B, and 2M have a dominant inheritance pattern while type 3 has a recessive pattern. While the primary diagnosis can often be established with the assessment of VWF and Factor VIII levels, molecular genetic assessment is imperative for carrier detection, genetic counselling, prenatal diagnosis, and evaluation of genotype–phenotype correlation.

Aims: To evaluate the parents of a cohort of VWD patients so that inheritance patterns can be better understood in settings where molecular genetic testing is not feasible or routinely done.

Methods: Twenty-six patients who were diagnosed as VWD between November 2021 and November 2023, and with availability of parents for concurrent evaluation were included in the study. Complete coagulation workup included skin bleeding time, Platelet Function Analyser 200 (PFA-200), Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), Ristocetin Cofactor assay (VWF:RCo, Sysmex 2400, Kobe, Japan), Von Willebrand Antigen (VWF:Ag), Factor assays and Ristocetin-induced platelet aggregation. Parents were evaluated using APTT, Factor VIII, VWF:RCo, and VWF:Ag. If any of these tests gave subnormal results, they were considered to be probable carriers.

Results: Parental evaluation revealed that at least one parent would be a probable carrier in 16 of 26 cases (61.54%) and this was most pronounced in Type 3 VWD (13/20 cases; 65%). However, on analyzing the various test results, a reduction in levels of VWF:RCo and VWF:Ag in parents of type 1 VWD were the most observed findings.

Conclusion(s): Genetic testing for VWD is generally not indicated except for specific cases in which the results of the test would make a difference in the patient’s treatment or be relevant for genetic counselling. Concurrent parental evaluation is a simple practice which can be useful in resource-limited settings to indirectly infer carrier status.