Von Willebrand Disease Case Study
Von Willebrand Factor (VWF) is essential for proper hemostasis. It serves as a carrier protein for factor VIII and also aids in platelet adherence to damaged endothelium. Von Willebrand Disease (VWD) may result from congenital absence of VWF, structural or functional abnormalities or mutations leading to mild decreases in expression of VWF. Type 3 VWD is an autosomal recessive disorder, which accounts for only 1% of patients with VWD and is characterized by a virtual absence of VWF and low levels of Factor VIII.
To describe a case of Type 3 VWD including the presentation, diagnosis and clinical course.
Design/Method: Case Report.
A 4 month old female presented with a history of 8 hours of persistent bleeding from an injection site following vaccination administration. At that time, the patient's platelet count and PT/PTT were normal. She had a few intermittent episodes of persistent bleeding with minor abrasions and had labs repeated at the age of 4 months which were significant for a prolonged PTT of 59.5 seconds with normal PT and platelet count. Factor VIII level was <1% and VWF activity was <15%.
A complete Von Willebrand panel was sent to Mayo Medical Labs and showed a Factor VIII level of 2%, VWF antigen 6%, VWF activity of 8, and an absence of VWF multimers. Confirmatory VWF full gene sequence analysis testing was sent to Blood Center of Wisconsin and showed a heterozygous sequence variant, c.2435delC, in the VWF gene consistent with a diagnosis of VWD Type 3. VWF full gene sequence analysis was also sent on both parents. Mother's results showed that she is a carrier of the same VWF gene sequence variant. Father's results were negative. Given the patient only has a heterozygous sequence variant yet still has expression of VWD, gene duplication testing was sent to Blood Center of Wisconsin to look for possible duplication of this area. Results of this testing showed that the patient had two pathogenic variants, one on each allele: heterozygous c.243delC in exon 18 and a deletion involving exon 6 in the VWF gene.
This case represents the clinical presentation and diagnosis of a patient with Type 3 VWD. While VWD is not uncommon, diagnosis of VWD Type 3 is quite rare. VWD Type 3 is inherited in an autosomal recessive fashion. In the case of our patient, only one parent was identified as a carrier of the same gene sequence mutation. Therefore, the second pathogenic variant resulting in VWD Type 3 was found to be a de novo deletion, further adding to the uniqueness of this case.
Disclosures No relevant conflicts of interest to declare.
↵* Asterisk with author names denotes non-ASH members.
- © 2016 by The American Society of Hematology
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