Patients with multiple types of Ehlers-Danlos syndrome (EDS) exhibit a variety of bleeding symptoms that range from mild to life-threatening episodes, according to a study published in the Journal of Thrombosis and Haemostatis.
The 2017 EDS International Classification has defined 13 types of EDS, based on clinical criteria and genetic mutations. Although clinical criteria across EDS types vary, all types are associated with joint hypermobility, skin hyperelasticity, and chronic pain. Easy bruising is a major diagnostic criterion for four types of EDS and a minor criterion for five types of EDS, and bleeding symptoms are often observed in patients with hypermobile EDS (hEDS).
However, abnormal bleeding and bruising may be overlooked because of the mild nature of symptoms and the hereditary nature of the disorder, potentially delaying diagnosis. There is still a lack of definitive understanding of the frequency, severity, and types of bleeding complications in patients with different types of EDS.
Using the International Society of Thrombosis and Haemostatis bleeding assessment tool (ISTH-BAT), researchers sought to characterize and evaluate hemorrhagic symptoms in a cohort of patients with common types of EDS. Inclusion criteria for the study included a diagnosis of an inherited or acquired coagulation or platelet disorder, hereditary hemorrhagic telangiectasia, a history of thrombosis, or an autoimmune disease.
Fifty-two patients (96% female; mean age = 33 years) with classical (cEDS; 27%), classical-like (cIEDS; 21%), hEDS (48%), or vascular EDS (vEDS; 2%) participated in the study. Participants were clinically evaluated and questioned on their and their family’s medical histories. A healthy control group of 52 individuals was matched by age and gender. All study participants completed the ISTH-BAT.
Statistical analysis showed a mean ISTH-BAT score of 0.1 for the healthy control group and 9.1 for patients with EDS and no significant difference in mean ISTH-BAT scores between patients with cEDS, hEDS, cIEDS, and vEDS. An abnormal score was obtained in 62% of patients with EDS and none in the healthy control group, and almost all patients with EDS reported mild or moderate bleeding symptoms. The most frequent bleeding symptoms in the EDS group were bruising, muscle hematomas, menorrhagia, epistaxis, bleeding from the oral cavity, and bleeding after tooth extraction.
“Although hemorrhagic diathesis in EDS is characterized as a mild phenotype, our results show that up to 14% of menorrhagia in the female population had life-threatening severity,” said lead study author Mariia Kumskova, MD, of the University of Iowa in Iowa City. “Furthermore, nose bleeding in EDS was characterized as severe or life-threatening in 23% of instances. Our findings demonstrate that EDS carries a high risk of hemorrhagic complication, including bleeding after surgeries and teeth extractions. These data should raise awareness and improve the timely diagnosis and treatment of EDS across different specialties.”
One limitation of this study design was that patients with EDS were self-identified, increasing the likelihood of selection bias toward more symptomatic patients.
The researchers state that, although the etiology of bleeding in EDS remains incompletely defined and is likely multifactorial, this study substantiates EDS as a congenital connective tissue disorder that carries a high risk of hemorrhagic complications. They note that, given that the only bleeding symptom included in the current EDS International Classification diagnostic criteria is easy bruising, these findings suggest that other bleeding symptoms should be considered for inclusion in a revised EDS classification.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Kumskova M, Flora GD, Staber J, et al. Characterization of bleeding symptoms in Ehlers-Danlos syndrome [published online ahead of print, 2023 April 17]. J Thromb Haemost. doi:10.1016/jtha.2023.04.004.
