title: Clinical syndromes associated with acquired antithrombin deficiency via microvascular leakage and the related risk of thrombosis.
abstract: Antithrombin (AT) is a 65kDa glycoprotein belonging to a group of inhibitory factors known as serpins (serine protease inhibitors). It plays a critical role in the inhibition of coagulation and inflammation processes within the environment of the vascular endothelium. Inadequate levels of functional AT in plasma results in an increased risk of thrombotic events, both venous and arterial. AT deficiency can be inherited or acquired. Congenital AT deficiency is the most severe inherited thrombophilic condition with an odds ratio of 20 for the increased risk of venous thrombosis. Acquired AT deficiency occurs in a variety of physiologic and pathologic medical conditions with similar risks of increased thrombosis. In this article, we review clinical settings characterized by an acquired AT deficiency largely or partly subsequent to protein microvascular leakage. Other different mechanisms of AT depletion are implied in some clinical conditions together with endothelial loss, and, therefore, outlined. In addition, we provide a description of the current knowledge on the specific mechanisms underlying endothelial AT leakage and on the consequences of this protein decrease, specifically looking at thrombosis. We identify potential directions of research that might prove useful in patients with acquired AT deficiency.
authors.affiliation: Yale Women and Children's Center For Blood Disorders, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, USA; Department of Obstetrics and Gynecology, University of Milan-Bicocca, via Pergolesi 33, Monza, MB, Italy. Electronic address: sara.ornaghi@gmail.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Ornaghi
authors.affiliation: Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Kurt T
authors.initials: KT
authors.lastname: Barnhart
authors.affiliation: rEVO Biologics 175 Crossing Boulevard, Framingham, MA 01702, USA.
authors.forename: Johan
authors.initials: J
authors.lastname: Frieling
authors.affiliation: rEVO Biologics 175 Crossing Boulevard, Framingham, MA 01702, USA.
authors.forename: James
authors.initials: J
authors.lastname: Streisand
authors.affiliation: Yale Women and Children's Center For Blood Disorders, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Paidas
mesh_terms: D020152:Antithrombin III Deficiency / Q000097:blood* / Q000150:complications*; D001777:Blood Coagulation / Q000502:physiology; D006801:Humans; D013577:Syndrome; D013927:Thrombosis / Q000209:etiology*
keywords: Antithrombin; Coagulation; Inflammation; Thrombosis; Vascular permeability