Abstract
Intravascular and extravascular fibrin formation are characteristic findings in patients with sepsis, suggesting that the activation of coagulation and the inhibiton of fibrinolysis are important in the pathogenesis of sepsis. Activation of coagulation during sepsis is primarily driven by the tissue factor (TF) pathway, while inhibition of fibrinolysis is primarily due to increases in plasminogen activator inhibitor -1(PAI-1). Downregulation of the anticoagulant Protein C pathway also plays an important role in the modulation of coagulation and inflammation in sepsis. Recent advances in the understanding of pathogenetic mechanisms of coagulation and fibrinolysis in sepsis may have therapeutic implications. Recombinant human activated protein C (rhAPC) is currently the only pharmacologic therapy that has been shown to reduce mortality in adults with severe sepsis, highlighting the importance of coagulation and fibrinolysis as a therapeutic target in sepsis. This review summarizes recent basic and clinical findings with regard to the role of the coagulation cascade in sepsis and explores potential therapeutic targets in the coagulation and fibrinolytic pathways in the management of sepsis.
Keywords: Coagulation, Sepsis, pathogenesis, tissue factor (TF), inflammation, activated protein C, fibrinolysis
Current Pharmaceutical Design
Title: The Coagulation Cascade in Sepsis
Volume: 14 Issue: 19
Author(s): Ling Wang, Julie A. Bastarache and Lorraine B. Ware
Affiliation:
Keywords: Coagulation, Sepsis, pathogenesis, tissue factor (TF), inflammation, activated protein C, fibrinolysis
Abstract: Intravascular and extravascular fibrin formation are characteristic findings in patients with sepsis, suggesting that the activation of coagulation and the inhibiton of fibrinolysis are important in the pathogenesis of sepsis. Activation of coagulation during sepsis is primarily driven by the tissue factor (TF) pathway, while inhibition of fibrinolysis is primarily due to increases in plasminogen activator inhibitor -1(PAI-1). Downregulation of the anticoagulant Protein C pathway also plays an important role in the modulation of coagulation and inflammation in sepsis. Recent advances in the understanding of pathogenetic mechanisms of coagulation and fibrinolysis in sepsis may have therapeutic implications. Recombinant human activated protein C (rhAPC) is currently the only pharmacologic therapy that has been shown to reduce mortality in adults with severe sepsis, highlighting the importance of coagulation and fibrinolysis as a therapeutic target in sepsis. This review summarizes recent basic and clinical findings with regard to the role of the coagulation cascade in sepsis and explores potential therapeutic targets in the coagulation and fibrinolytic pathways in the management of sepsis.
Export Options
About this article
Cite this article as:
Wang Ling, Bastarache A. Julie and Ware B. Lorraine, The Coagulation Cascade in Sepsis, Current Pharmaceutical Design 2008; 14 (19) . https://dx.doi.org/10.2174/138161208784980581
DOI https://dx.doi.org/10.2174/138161208784980581 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Therapeutic Challenges in Neuroendocrine Tumors
Anti-Cancer Agents in Medicinal Chemistry Antimicrobial Drug Interactions in the Critically Ill Patients
Current Clinical Pharmacology Impaired Neural Transmission and Synaptic Plasticity in Superior Cervical Ganglia from β-Amyloid Rat Model of Alzheimers Disease
Current Alzheimer Research Vascular Endothelial Growth Factor (VEGF) Biochemistry and Development of Inhibitory Drugs
Current Drug Therapy Antidiabetic Potential of Fabaceae Family: An Overview
Current Nutrition & Food Science Models to Study Atherosclerosis: A Mechanistic Insight
Current Vascular Pharmacology Adrenomedullin in Heart Failure: Molecular Mechanism and Therapeutic Implication
Current Hypertension Reviews Modulation of Neutrophil Function by Hormones
Current Immunology Reviews (Discontinued) Intra-arterial Instillation of a Nociceptive Agent Modulates Cardiorespiratory Parameters Involving 5-HT3 and TRPV1 Receptors in Anesthetized Rats
Cardiovascular & Hematological Disorders-Drug Targets Cardiovascular Diseases and the Nitric Oxide Pathway
Current Vascular Pharmacology Pharmacological Therapy in Children with Atrioventricular Reentry: Which Drug?
Current Pharmaceutical Design Effects of Remifentanil on the Cardiac Conduction System. Our Experience in the Study of Remifentanil Electrophysiological Properties
Current Pharmaceutical Design Neurotrophic and Neuroprotective Effects of Muscle Contraction
Current Pharmaceutical Design Snake Venom: From Deadly Toxins to Life-saving Therapeutics
Current Medicinal Chemistry Redefining the Role of Long-Acting Phosphodiesterase Inhibitor Tadalafil in the Treatment of Diabetic Erectile Dysfunction
Current Diabetes Reviews The Role of Metabolizing Enzymes and Transporters in Antiretroviral Therapy
Current Topics in Medicinal Chemistry Methylenedioxy- and Ethylenedioxy-Fused Indolocarbazoles: Potent Human Topoisomerase I Inhibitors and Antitumor Agents
Anti-Cancer Agents in Medicinal Chemistry Radial vs Femoral Approach in Acute Coronary Syndromes: A Meta- Analysis of Randomized Trials
Current Vascular Pharmacology Potential Strategies for Minimizing Mechanism-Based Inhibition of Cytochrome P450 3A4
Current Pharmaceutical Design Reviewing the Cardiovascular Complications of HIV Infection After the Introduction of Highly Active Antiretroviral Therapy
Current Drug Targets - Cardiovascular & Hematological Disorders