Chapter category: Coagulation
Regulation of Coagulation and Inflammation by the Thrombomodulin/Protein C System in Sepsis
Molecular Mechanisms of Disseminated Intravascular Coagulation
Edited by: Hugo ten CateISBN: 1-58706-058-2
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Chapter authors:
Kenji Okajima
Thrombomodulin (TM) plays a role in regulation of the coagulation system not only by decreasing the procoagulant activities of thrombin, but by activation of protein C (PC) to form activated protein C. Activated protein C (APC), which inactivates factors (F.) Va and F.VIIIa, regulates inflammation by inhibiting leukocyte activation, thereby reducing organ injury and microthombus formation in sepsis. Dysfunction of the TM/PC system is induced by proinflammatory cytokines and other inflammatory mediators derived from activated neutrophils, leading to the development of DIC associated with sepsis. These observations raise the possibility that exogenous administration of TM and APC may ameliorate both microthrombus formation and organ failure in sepsis This chapter will describe: 1) the role of the TM/PC system in regulation of coagulation and inflammation in sepsis; 2) mechanisms by which the function of the TM/PC system is impaired; and 3) the possible usefulness of substitution of TM and APC as new strategies for treatment of organ failure and DIC in sepsis.
Additional chapters from this book:
Lessons from Venous Thrombosis and Disseminated Intravascular Coagulation: A Synthesis of Pathophysiological Mechanisms of Prothrombotic States
Hugo ten Cate and William C. Aird
Thrombosis can be defined as formation of an intravascular clot, consisting of cells, fibrin, and activated clotting proteins, interacting with the vessel wall, and partly or completely obs...
Treatment Strategies in DIC
Marcel Levi and Hugo ten Cate
The proper management of patients with DIC remains controversial. The clinical picture of simultaneously occurring systemic thrombotic depositions and bleeding due to consumption does not d...
Disseminated Intravascular Coagulation (DIC): Introduction
Marcel Levi and Hugo ten Cate
One of the first reports on disseminated intravascular coagulation in the medical literature comes from Dupuy in 1834, who describes the effect of the intravenous injection of brain material i...
Disease Specific Mechanisms of Disseminated Intravascular Coagulation
J.A. Kremer Hovinga, J.M.M. Otten, M.M. Levi, and H. ten Cate
Disseminated intravascular coagulation (DIC) is defined as an acquired syndrome characterized by widespread activation of coagulation leading to intravascular formation of fibrin and thromboti...
Blood Borne Tissue Factor (Including Microparticles)
Bjarne Østerud and Erik Bjørklid
Minor amounts of biologically active tissue factor (TF) are always constitutively present in circulating blood of healthy individuals. In various diseases, including those underlying the in...
Endothelial Cell Perturbation and Disseminated Intravascular Coagulation
Nicola Semeraro and Mario Colucci
It has long been recognized that the vascular endothelium is a major target of bacterial endotoxin and of a variety of microorganisms, and that damage to endothelial cells (ECs) is a hallmark ...
Genetic Risk Factors for Disseminated Intravascular Coagulation
D.W. Sommeijer and P.H. Reitsma
Disseminated intravascular coagulation (DIC) is a life threatening condition that occurs due to a severe imbalance of the coagulation system. DIC is characterized by the combined occurrence of...
Regulation of Coagulation and Inflammation by the Thrombomodulin/Protein C System in Sepsis
Kenji Okajima
Thrombomodulin (TM) plays a role in regulation of the coagulation system not only by decreasing the procoagulant activities of thrombin, but by activation of protein C (PC) to form activated protein C...
DIC at the Intersection of the Thrombotic, Fibrinolytic and Inflammatory Axes
Sean P. Mazer, David J. Pinsky
Disseminated intravascular coagulation (DIC) is a common clinical syndrome with dichotomous presentations of hemorrhage and thrombosis with a common underlying pathophysiology. As a syndrome, DIC pres...
Cytokines as Regulators of Coagulation
Tom van der Poll, Evert de Jonge, Hugo ten Cate an
Severe infection is frequently accompanied by disturbances in the hemostatic balance. The most severe manifestation of these disturbances is known as the clinical syndrome of disseminated intravascula...
Factor XI, TAFI and DIC
Monique C. Minnema, Joost C.M. Meijers
Since 1991, the opinion on the role of factor XI in coagulation has changed from an intermediary between the contact system and factor IX to an important protease in both the coagulation and the fibri...
Contributions of the Plasma Kallikrein/Kinin System to Disseminated Intravascular Coagulation
Alvin H. Schmaier
Disseminated intravascular coagulation (DIC) is a clinicopathologic state that arises from an imbalance between the degree of thrombin and plasmin formation. Most cases of DIC arise from tissue injury...
The Pleiotropic Effects of Tissue Factor
Henri H. Versteeg, C. Arnold Spek
Tissue factor, a 47 kDa integral membrane glycoprotein, is the primary initiator of the coagulation cascade. Interaction of TF with factor VIIa, which circulates at low levels in the bloodstream, resu...
Regulation of Tissue Factor Expression
Wolfram Ruf, Matthias Riewald
The cellular initiation of the coagulation protease cascade by tissue factor (TF) is the central pathway that initiates disseminated intravascular coagulation and contributes to lethality associated w...
