Chapter category: Coagulation
Lessons from Venous Thrombosis and Disseminated Intravascular Coagulation: A Synthesis of Pathophysiological Mechanisms of Prothrombotic States
Molecular Mechanisms of Disseminated Intravascular Coagulation
Edited by: Hugo ten CateISBN: 1-58706-058-2
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Chapter authors:
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 obstructing the bloodstream. Thrombosis may arise in arteries, veins, capillaries or some combination of blood vessel types. Isolated arterial thrombi usually develop in association with underlying atherosclerotic lesions, while venous thrombi more commonly arise in the absence of vessel wall damage. Capillary thrombi are characteristic of disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP) and heparin induced thrombocytopenia (HIT). Combined arterial and venous thrombi are seen in patients with elevated levels of homocysteine, antiphospholipid antibody syndrome or myeloproliferative disorders. Finally thrombi may arise simultaneously in arteries, veins and capillaries in some patients with DIC, HIT and catastrophic antiphospholipid antibody syndrome.
TTP, HIT and antiphospholipid antibody syndrome are distinguished by their unique epidemiology, pathophysiology and pathology and will not be discussed in the present chapter. Moreover, a review of arterial thrombi associated with coronary artery disease, cerebrovascular disease and peripheral vascular disease is beyond the scope of this review. In this paper, we will focus on the syndromes of DIC and deep venous thrombosis (DVT). We will propose that venous thrombosis and DIC are linked by common pathophysiological mechanisms. In support of this hypothesis, we will discuss the importance of interplay between the inflammatory and hemostatic pathways and the critical role of the endothelium in determining local thrombotic phenotypes.
Research in the field of deep venous thrombosis has focused primarily on epidemiological, diagnostic and therapeutic questions. In contrast, studies in animal and human models of sepsis have provided important insight about the pathophysiology of DIC. Indeed, these investigations have uncovered critical links that exist between the coagulation, fibrinolytic and inflammatory pathways. We believe that the application of these principles to venous thrombosis will provide a valuable framework for future studies. These considerations form the basis for the present paper.
Hugo ten Cate
William C. Aird
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 obstructin...
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 directly ...
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 in anima...
Disease Specific Mechanisms of Disseminated Intravascular Coagulation
J.A. Kremer Hovinga, J.M.M. Otten, M.M. Levi and Hugo 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 thrombotic occlus...
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 induction ...
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 of Gram...
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 activat...
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 and 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 and Hugo ten Cate
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 and 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 and 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 and 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...
