Recurrent venous thrombosis in Ehlers-Danlos syndrome type III: an atypical manifestation

Hemostatic abnormalities and impaired platelet function have been described in patients affected by connective tissue disorders. We observed a moderate bleeding tendency in patients affected by Collagen VI-related disorders and investigated the defects in platelet functionality whose mechanisms are unknown. We demonstrated that megakaryocytes express Collagen VI that is involved in the regulation of functional platelet production. By exploiting a Collagen VI null mouse model (Col6a1-/-), we found that Collagen VI null platelets display significantly increased susceptibility to activation and intracellular calcium signaling. Col6a1-/- megakaryocytes and platelets showed increased expression of STIM1 and ORAI1, the components of Store-Operated Calcium Entry (SOCE), and activation of the mTOR signaling pathway. In vivo mTOR inhibition by rapamycin reduced both STIM1 and ORAI1 expression and calcium flows, resulting in a normalization of platelet susceptibility to activation. These defects were cell-autonomous, as transplantation of lineage-negative bone marrow cells from Col6a1-/- mice into lethally irradiated wild-type animals showed the same alteration in SOCE and platelet activation as compared to Col6a1-/- mice. Peripheral blood platelets of patients affected by Collagen VI-related diseases, Bethlem myopathy and Ullrich congenital muscular dystrophy, displayed increased expression of STIM1 and ORAI1 and were more prone to activation. Altogether, these data demonstrate the importance of Collagen VI in the production of functional platelets by megakaryocytes in mouse models and in Collagen VI-related diseases.

show abstract

Ablation of collagen VI leads to the release of platelets with altered function

Abbonante

Gruppi

Battiston

et al. 2021

Blood Advances

View full text Add to dashboard Cite

show abstract

Renal Infarction in Vascular Ehlers-Danlos Syndrome

Lee¹,

Kim²,

Yang³

et al. 2022

Korean J Med

View full text Add to dashboard Cite

Renal infarction is a condition caused by sudden disturbance of renal arterial blood flow, which occurs frequently in cardioembolic disease, renal artery injury (trauma, Marfan syndrome, rarely Ehlers-Danlos syndrome), and in association with a hypercoagulable state. Ehlers-Danlos syndrome is a rare hereditary connective tissue disease characterized by skin fragility, hyperelasticity, hypermobility of small joints, and easy bruising. Among the subtypes, vascular Ehlers-Danlos syndrome is a very rare genetic disease caused by a mutation in the <i>COL3A1</i> gene. As blood vessels are fragile due dysfunctional collagen synthesis, complications of bleeding due to arterial dissection or rupture are common in patients with this disease. Here, we report a case of vascular Ehlers-Danlos syndrome diagnosed based on a renal infarction caused by thrombus and renal artery injury; we also present a review of the relevant literature.

show abstract

Pulmonary hypertension: when the acute event leads to diagnosis. Case report in a patient with Ehlers-Danlos syndrome.

et al. 2020

View full text Add to dashboard Cite

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a pulmonary vascular pathology caused by the chronic obstruction of the major pulmonary arteries, usually being the consequence of recurrent episodes of pulmonary embolism. Such events are usually unknown; the delay in such a diagnosis can therefore lead to a deterioration of the clinical picture, worsening the overall prognosis. This is a case of a 55-year-old man who came to the Emergency Room (ER) because of an acute exacerbation of chronic dyspnea, that he experienced for several years, in the absence of an explanatory diagnosis. Acute pulmonary embolism was diagnosed in the setting of the ER, with bedside echography resulting to be crucial to the work up. A multidisciplinary approach allowed proper treatment, management and a favourable outcome.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Recurrent venous thrombosis in Ehlers-Danlos syndrome type III: an atypical manifestation

Cited by 3 publications

References 4 publications

Ablation of collagen VI leads to the release of platelets with altered function

Ablation of collagen VI leads to the release of platelets with altered function

Renal Infarction in Vascular Ehlers-Danlos Syndrome

Pulmonary hypertension: when the acute event leads to diagnosis. Case report in a patient with Ehlers-Danlos syndrome.

Contact Info

Product

Resources

About