Thrombin mediates the extraintestinal thrombosis associated with experimental colitis
Hideo Yoshida1, Janice Russell, D Neil Granger
1Dept. of Molecular and Cellular Physiology, LSU Health Sciences Ctr., Shreveport, LA 71130-33932, USA.
American Journal of Physiology. Gastrointestinal and Liver Physiology
|September 6, 2008
Summary
Thrombin significantly accelerates blood clot stabilization in distant vessels during experimental colitis. Antithrombin agents, like hirudin, effectively prevent this thrombosis, suggesting therapeutic potential for inflammatory bowel disease patients.
Area of Science:
- Vascular biology
- Coagulation cascade
- Inflammatory diseases
Background:
- Intestinal inflammation is linked to hypercoagulable states.
- Tissue factor and protein C pathway involvement suggests thrombin's role.
Purpose of the Study:
- To investigate thrombin's role in extraintestinal thrombosis during experimental colitis.
- To quantify thrombus formation in DSS-induced colitis models.
Main Methods:
- Utilized a light/dye endothelial injury model in mice with dextran sodium sulfate (DSS)-induced colitis.
- Administered antithrombin agents: hirudin, heparin, and antithrombin III.
- Quantified thrombus initiation (time of onset) and propagation/stabilization (time to blood flow cessation).
Main Results:
- Thrombus formation was accelerated in colitic mice.
- Antithrombin agents did not significantly alter thrombus initiation.
- Hirudin, heparin, and antithrombin III largely prevented accelerated thrombus stabilization, with hirudin providing complete protection.
Conclusions:
- Thrombin plays a significant role in the propagation/stabilization phase of colitis-associated thrombogenesis.
- Antithrombin agents show therapeutic potential for reducing thromboembolism risk in inflammatory bowel disease.
Related Concept Videos
01:20Inflammatory Bowel Disease II: Ulcerative Colitis
Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by continuous mucosal inflammation that typically begins in the rectum and extends proximally in a uniform pattern. Its pathogenesis involves a complex interplay of genetic predisposition, immune dysregulation, and environmental influences. These factors converge to impair the colon’s epithelial defenses and promote an exaggerated inflammatory response against luminal contents.Breakdown of the Mucosal BarrierA...
01:25Inflammatory Bowel Disease III: Crohn's Disease
Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
Introduction
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
01:20Extrinsic and Intrinsic Pathways of Hemostasis
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which forms a...
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which forms a...
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
01:20Inflammatory Bowel Disease IV: Clinical Manifestations
Inflammatory bowel disease (IBD) encompasses two major chronic disorders—ulcerative colitis and Crohn’s disease—each characterized by relapsing episodes of gastrointestinal inflammation. Although they share certain clinical features, their patterns of involvement and manifestations differ in ways that aid diagnosis and guide management.Ulcerative ColitisUlcerative colitis is limited to the colon and rectum and involves continuous inflammation of the mucosal layer. The disease course is marked...