Assessment of rare bleeding disorders in adolescents with heavy menstrual bleeding

• Published in: Haemophilia : the official journal of the World Federation of Hemophilia 2024-03, Vol.30 (2), p.490-496
• Main Authors: Sharma, Ruchika, Johnson, Victoria, Pan, Amy, Sellers, Austin, Betensky, Marisol, Goldenberg, Neil, Flood, Veronica H.
• Format: Article
• Language: English
• Subjects: Adolescent; Adolescents; Bleeding; bleeding disorder of unknown cause; Blood Coagulation Disorders - diagnosis; Coagulation; Female; Fibrin; Fibrinolysis; Genetic diversity; Genotypes; heavy menstrual bleeding; Hemophilia; Hemorrhage - complications; Hemorrhagic Disorders - epidemiology; Humans; Lysis; Menorrhagia - complications; Menstruation; Next-generation sequencing; Phenotypes; Population studies; Prospective Studies; Thrombin
• ISSN: 1351-8216; 1365-2516
• DOI: 10.1111/hae.14961

Introduction There are a significant number of patients with mucocutaneous bleeding, specifically heavy menstrual bleeding (HMB), who do not have a diagnosed bleeding disorder. These patients receive nontargeted interventions and may have suboptimal treatments. Functional assays, particularly for fibrinolytic and rare platelet function defects, are not robust and not readily available. Aim We aimed to prospectively evaluate the prevalence of genetic defects associated with rare bleeding disorders and describe alterations of coagulation and fibrinolysis in a cohort of adolescents with HMB. Methods We performed a prospective observational cohort study of patients with HMB and unexplained bleeding. The study utilized a next generation sequencing panel and investigational global assays of coagulation and fibrinolysis. Additionally, specific functional assays were performed to help characterize novel variants that were identified. Results In 10 of the 17 patients (∼59%), genetic variants were identified on molecular testing. Thrombin generation by calibrated thromboelastography was not significantly altered in this patient population. The clot formation and lysis assay showed a trend towards increased fibrinolysis with rapid phase of decline in 23% of the patients. Further corresponding functional assays and study population are described. Conclusion Our study describes a unique correlative model in a homogenous cohort of patients with HMB and unexplained bleeding which may inform future diagnostic algorithms, genotype–phenotype correlations as well as aid in specific targeted treatment approaches. Larger future studies may inform risk stratification of patients and improve health related outcomes in patients with HMB.