Thrombin mediates the extraintestinal thrombosis associated with experimental colitis.

Abstract

Recent evidence implicating tissue factor and the protein C pathway in the hypercoagulable state associated with intestinal inflammation suggests that thrombin is likely to contribute to this response. The objective of this study was to assess the role of thrombin in the extraintestinal thrombosis associated with experimental colitis. Thrombus formation was quantified in microvessels of the cremaster muscle in mice with dextran sodium sulfate (DSS)-induced colonic inflammation. The light/dye endothelial injury model was used to elicit thrombus formation in DSS colitic mice treated with either hirudin, heparin, or antithrombin III. The initiation and propagation/stabilization phases of thrombus formation were quantified using the time of onset of the thrombus and time to blood flow cessation, respectively. Thrombus formation was accelerated in arterioles of DSS colitic mice, as exhibited by significant reductions in the time of thrombus initiation and propagation/stabilization. Colitic mice treated with hirudin, heparin, or antithrombin III did not exhibit a significant change in the time of onset of the thrombus compared with untreated colitic mice. However, all three antithrombin agents largely prevented the DSS-induced reduction in the time to flow cessation following light/dye injury, with hirudin offering complete protection. These findings indicate that thrombin plays a major role in the extraintestinal thrombus formation associated with experimental colitis. Thrombin appears to contribute to the propagation/stabilization, rather than initiation, phase of the colitis-associated thrombogenesis at the distant vascular site. The results support the therapeutic use of antithrombin agents for reducing the risk of thromboembolism in patients with inflammatory bowel disease.

• Authors: Hideo Yoshida, Janice Russell, D Neil Granger
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 295 Issue 5 Pg. G904-8 (Nov 2008) ISSN: 0193-1857 [Print] United States
• PMID: 18772359 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Hirudins
• Heparin
• Dextran Sulfate
• Thrombin

Topics

• Animals
• Arterioles (physiology)
• Colitis (chemically induced, metabolism)
• Dextran Sulfate (toxicity)
• Heparin (pharmacology)
• Hirudins (pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Muscle, Skeletal (pathology)
• Thrombin (metabolism)
• Thrombosis (drug therapy, metabolism, pathology)
• Venules (physiology)