PB0705 - East Texas Bleeding Disorder – A Novel Bleeding Disorder

Background: A large kindred from east Texas, USA was reported with a novel moderately severe bleeding disorder affecting both males and females given the autosomal dominant trait from a gain-of-function mutation in the F5 gene. The truncated FV, termed FV-short, forms a high-affinity complex with tissue factor pathway inhibitor (TPFI) generating a significant increase in its level, thus inhibiting coagulation. Clinical characteristics include easy bruising, epistaxis, menorrhagia, and bleeding related to surgical procedures and significant trauma.

Aims: Diagnosis and treat affected family members of the east Texas cohort.

Methods: All members of the family were invited to Gulf States Hemophilia and Thrombophilia Center for a multidisciplinary evaluation, including ISTH-SCC- Bleeding Assessment (BAT), coagulation studies, and targeted variant testing for the F5 gene c.2350A>G, p. Ser784Gly mutation.

Results: Four generations, a total of 31 patients, were assessed resulting in 22 affected family members with positive variant findings for c.2350A>G, p. Ser784Gly mutation. Forty percent of the cohort was found to have at least one abnormal routine coagulation study, with forty percent displaying both prolonged PT and PTT, and twenty percent resulting in unaffected coagulation studies. Highest BAT scores within the cohort were noted in both the female and male population ≥ 18 years of age (Highest Female ISTH BAT- 26, Highest Male ISTH BAT- 24). Children < 18 years of age were noted to have the lowest BAT scores between 0-8.

Conclusion(s): Given rarity of the disease and management challenges a multidisciplinary approach to care is recommended, ideally at a Hemophilia Treatment Center (HTC). Access to a team of experts with specialized knowledge and skill is essential in providing ongoing patient education including prevention, recognition and treatment of bleeding. As TFPI levels are not readily accessible and routine coagulation studies may be unaffected, genetic testing should be pursued for diagnosis.