Rare Coagulation Disorders: A Comprehensive Study from the Largest Hospital in Latin America
Authors: Erthal Carolina Wermelinger , Ayres Gabriela , Nobrega Thais Dourado Reis , Rothschild Cynthia , Stefanello Bianca , Okazaki Erica , Prestes Paula , Villaça Paula Ribeiro , Orsi Fernanda A. 
Published: December 2024

Introduction: Rare inherited bleeding disorders (RIBD) represent approximately 5% of hereditary coagulopathies and include deficiencies of coagulation factors other than VII, IX, and von Willebrand factor. The global prevalence of RIBD varies by region and type of deficiency, with rates as low as 1 in 2,000,000 individuals. In low- and middle-income countries, such as Brazil, there is a paucity of data pertaining to the clinical presentation and the challenges in diagnosing these diseases, particularly within the public health system and its constrained resources. The objective of this study is to describe the clinical phenotype, as well as the patient journey to diagnosis and treatment, with the ultimate goal of raising awareness of RIBD in these regions.
Materials and Methods: This is a case series study including all patients with RIBD followed in the largest hospital complex in Latin America, located in São Paulo, Brazil. Data collected included demographics, bleeding episodes, and severity according to the ISTH classification. This study was approved by the local ethics committee.
Results: A total of 82 patients with RIBD were included in the study. The cohort comprised 48 females (58.5%) and 34 males (41.5%), with a median age of 40 years (SD ± 21.0). The average age at diagnosis was 27 years (SD ± 22.2). The median time from diagnostic suspicion to confirmation among the studied cohort was 165 days (IQR 25-75% 33-1348 days). Regarding the types of coagulopathies, the distribution was as follows: factor VII deficiency was the most common, accounting for 43.9% of cases. This was followed by factor XI deficiency at 19.5%, heritable fibrinogen disorders at 13.4%, factor V deficiency at 7.3%, factor XIII deficiency at 4.9%, combined factor V and factor VIII deficiency at 4.9%, factor X deficiency at 3.7%, combined vitamin K-dependent clotting factors deficiency at 1.2% and factor XII deficiency at 1.2%. In terms of bleeding severity according to ISTH classification, major bleeding occurred in 23% of cases, clinically significant minor bleeding in 12% of cases and minor bleeding in 26%. Parental consanguinity was reported in 13.8% of patients. Patients with fibrinogen disorders, factor XIII deficiency, combined factor V and factor VIII deficiency, and vitamin K-dependent clotting factors deficiency exhibited the highest incidence of bleeding. Regarding major bleedings, the RIBD with the highest rate of bleedings was vitamin K deficiency (100%), followed by factor XIII deficiency (75%), factor X deficiency (66%), and fibrinogen disorders (66%).
Conclusion: Rare inherited bleeding disorders are diseases with highly diverse clinical manifestations and laboratory abnormalities, which present a significant challenge to diagnosis. The study highlights significant diagnostic delays experienced by patients with these diseases in a resource-limited country. Enhanced awareness and resource allocation are essential for improving the diagnosis and management of these disorders in developing countries.