Antithrombin: anti-inflammatory properties and clinical applications
- 1 January 2016
- journal article
- review article
- Published by Georg Thieme Verlag KG in Thrombosis and Haemostasis
- Vol. 115 (04), 712-728
- https://doi.org/10.1160/th15-08-0687
Abstract
Many humoral and cellular components participate in bidirectional communication between the coagulation and inflammation pathways. Natural anticoagulant proteins, including antithrombin (AT), tissue factor pathway inhibitor, and protein C, suppress proinflammatory mediators. Conversely, inflammation blunts anticoagulant activity and, when uncontrolled, promotes systemic inflammation-induced coagulation, such as those that occur in disseminated intravascular coagulation and severe sepsis. This review discusses the mechanisms of action and clinical use of AT concentrate in critically ill patients and in the settings of perioperative anticoagulation management for surgery and obstetrics. AT is a serine protease inhibitor with broad anticoagulant activity and potent anti-inflammatory properties. In clinical conditions associated with hereditary or acquired AT deficiency, administration of AT concentrate has been shown to restore proper haemostasis and attenuate inflammation. Of note, AT modulates inflammatory responses not only by inhibiting thrombin and other clotting factors that induce cytokine activity and leukocyte-endothelial cell interaction, but also by coagulation-independent effects, including direct interaction with cellular mediators of inflammation. An increasing body of evidence suggests that AT concentrate may be a potential therapeutic agent in certain clinical settings associated with inflammation. In addition to the well-known anticoagulation properties of AT for the treatment of hereditary AT deficiency, AT also possesses noteworthy anti-inflammatory properties that could be valuable in treating acquired AT deficiency, which often result in thrombotic states associated with an inflammatory component.Keywords
Funding Information
- IJW NIH (R01HL121232–01)
This publication has 107 references indexed in Scilit:
- Prevention, management and extent of adverse pregnancy outcomes in women with hereditary antithrombin deficiencyAnnals of Hematology, 2013
- Antithrombin Reduces Inflammation and Microcirculatory Perfusion Failure in Closed Soft-Tissue Injury and EndotoxemiaCritical Care Medicine, 2013
- A randomized, controlled, multicenter trial of the effects of antithrombin on disseminated intravascular coagulation in patients with sepsisCritical Care, 2013
- Antithrombin effect on coagulation and fibrinolytic profiles after living donor liver transplantation: a pilot studyInternational Journal of Laboratory Hematology, 2009
- THE RESPONSE OF ANTITHROMBIN III ACTIVITY AFTER SUPPLEMENTATION DECREASES IN PROPORTION TO THE SEVERITY OF SEPSIS AND LIVER DYSFUNCTIONShock, 2008
- Antithrombin III in critically ill patients: systematic review with meta-analysis and trial sequential analysisBMJ, 2007
- The Pathophysiology and Treatment of SepsisThe New England Journal of Medicine, 2003
- Familial antithrombin-III deficiency during cardiopulmonary bypass: a case reportPerfusion, 2000
- Antithrombin-III for the treatment of chemotherapy-induced organ dysfunction following bone marrow transplantationBone Marrow Transplantation, 1997
- Antithrombin III stimulates prostacyclin production by cultured aortic endothelial cellsBiochemical and Biophysical Research Communications, 1989