Hemostatic abnormalities in patients with Ehlers–Danlos syndrome

Abstract

Martinelli I. Hemostatic abnormalities in patients with Ehlers-Danlos syndrome. J Thromb Haemost 2018; 16: 2425-31. Essentials • Ehlers-Danlos Syndrome (EDS) is a rare heterogeneous group of inherited collagen disorders. • A cohort of EDS patients was investigated for bleeding tendency and hemostatic abnormalities. • EDS is associated with an increased risk of bleeding. • EDS patients have platelet function abnormalities, whose severity correlates with bleeding risk. Summary. Background: Ehlers-Danlos syndrome (EDS) includes a heterogeneous group of connective tissue disorders affecting skin, bones, vessels, and other organs. Patients with EDS have an increased risk of bleeding, but a comprehensive study of hemostasis in EDS patients is lacking. Objective: To investigate the bleeding tendency of a cohort of patients with EDS by using the Bleeding Assessment Tool of the ISTH, the bleeding severity score (BSS). Methods: The BSS was defined as abnormal when it was ≥ 4 in men and ≥ 6 in women. Patients with a bleeding tendency were compared with those without in terms of type and number of hemostatic abnormalities. Results: Fifty-nine of 141 patients with EDS (41.7%) had an abnormal BSS. Prothrombin time and activated partial thromboplastin time were slightly prolonged in 10 patients (7.1%) because of mild coagulation factor deficiencies, which were not responsible for the bleeding diathesis. von Willebrand factor antigen, ristocetin cofactor, endogenous thrombin potential and platelet count were normal in all patients. At least one platelet function abnormality was found in 53 patients (90%) with an abnormal BSS and in 64 (78%) with a normal BSS (adjusted odds ratio [OR] 2.55, 95% confidence interval [CI] 0.87-7.48). The risk of bleeding progressively increased with the number of platelet function abnormalities, reaching an OR of 5.19 (95% CI 1.32-20.45) when more than three abnormalities were detected. Conclusions: Our results show that nearly half of patients with EDS have an abnormal BSS, which, in 90% of cases, appear, at least in part, to be attributable to platelet function abnormalities. Abnormalities of primary hemostasis may contribute to the risk of bleeding in patients with EDS.

An update on the new classification of Ehlers‐Danlos syndrome and review of the causes of bleeding in this population

“…A recent case‐control study revealed that the prevalence of symptomatic joint hypermobility/suspected collagen disorders in patients referred to a bleeding disorder clinic was higher than in the age‐ and gender‐matched controls . Conversely, most hypermobile patients report symptoms of easy bruising and many have objective signs of abnormal bleeding . This suggests the contribution of abnormal collagen, which is reflected in symptomatic joint hypermobility, to the expression of bleeding tendency.…”

“…More recently, it has been shown that patients with vascular EDS have a platelet dysfunction, although this was studied only in a small cohort of patients and will need to be tested in a larger group of patients . A recent comprehensive study described significant platelet function abnormalities in patients with EDS and the absence of any consistent coagulation defect including thrombin generation …”

“…40 A recent comprehensive study described significant platelet function abnormalities in patients with EDS and the absence of any consistent coagulation defect including thrombin generation. 14…”

The challenge of simultaneous major aortic surgery and pectus excavatum repair in a patient with Ehlers‐Danlos type IV syndrome

“…| 251 bioprosthetic valve was chosen by the patient and to avoid the systemic anticoagulation. 6 Moreover, in the case of valve structural degeneration, usually within 12 to 20 years, the valve in valve transcatheter aortic valve implantation would be a safe and feasible option. 7 Likewise, we felt that due to the severity of the PE, the compression of the right ventricle combined with the fragility of tissues and the previous cosmetic intervention plus the desire of the patient for a permanent solution to his problem necessitated sternal bar support as a less invasive approach.…”

Features of Marfan syndrome not listed in the Ghent nosology – the dark side of the disease

“…In addition, it is interesting to note that the Ehlers-Danlos syndrome, another connective tissue disease which may be accompanied by aortic dilatation, can be associated with platelet dysfunction [373][374][375]. Platelet dysfunction could be found in Marfan patients as well, analyzed by the Multiplate and PFA 100 tests [353].…”