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A journey to vasculopathy in systemic sclerosis: focus on haemostasis and thrombosis

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Abstract

Systemic sclerosis is a multisystem connective tissue disease, characterized by endothelial autoimmune activation, along with tissue and vascular fibrosis leading to vasculopathy and to a progressive loss of angiogenesis. This condition further deranges the endothelial barrier favouring the opening of the endothelial junctions allowing the vascular leak in the surrounding tissues: this process may induce cell detachment which allows the contact between platelets and collagen present in the exposed subendothelial layer. Platelets first adhere to collagen via glycoprotein VI and then, immediately aggregate because of the release of von Willebrand factor which is a strong activator of platelet aggregation. Activated platelets exert their procoagulant activity, exposing on their membrane phospholipids and phosphatidylserine, enabling the adsorption of clotting factors ready to form thrombin which in turn drives the amplification of the coagulative cascade. An essential role in the activation of blood coagulation is the tissue factor (TF), which triggers blood coagulation. The TF is found abundantly in the subendothelial collagen and is also expressed by fibroblasts providing a haemostatic covering layer ready to activate coagulation when the endothelial injury occurs. The aim of this review is to focus the attention on the underlying mechanisms related to haemostasis and thrombosis pathophysiology which may have a relevant role in SSc as well as on a possible role of anticoagulation in this disease.

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Authors and Affiliations

  1. Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy

    Francesco Marongiu, Maria Filomena Ruberto & Doris Barcellona

  2. Thrombosis and Haemostasis Unit, Azienda Ospedaliero-Universitaria di Cagliari, Cagliari, Italy

    Francesco Marongiu & Doris Barcellona

  3. Internal Medicine Unit, SS Trinità Hospital of Cagliari, Cagliari, Italy

    Silvia Marongiu

  4. Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, Milan, Italy

    Marco Matucci Cerinic

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All Authors contributed to the review conception and design. Material preparation, data collection and analysis were performed by FM, MFR, SM, and DB. The first draft of the manuscript was written by FM and DB. MMC revised the manuscript. Figures are hand made by FM. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Doris Barcellona.

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Marongiu, F., Ruberto, M.F., Marongiu, S. et al. A journey to vasculopathy in systemic sclerosis: focus on haemostasis and thrombosis. Clin Exp Med 23, 4057–4064 (2023). https://doi.org/10.1007/s10238-023-01222-x

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