Chapter category: Coagulation
Contributions of the Plasma Kallikrein/Kinin System to Disseminated Intravascular Coagulation
Molecular Mechanisms of Disseminated Intravascular Coagulation
Edited by: Hugo ten CateISBN: 1-58706-058-2
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Chapter authors:
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 with formation of the factor VIIa-tissue factor complex and initiation of coagulation reactions. The plasma kallikrein/kinin system consists of three proteins, factor XII (FXII), prekallikrein (PK), and high molecular weight kininogen (HK) whose deficiencies are associated with abnormal surface-activated tests for blood coagulation, but not bleeding. Activation of the kallikrein/kinin system results in HK cleavage and bradykinin liberation that contributes to hypotension. There is no evidence that activation of the kallikrein/kinin system through factor XII or prekallikrein leads to thrombin formation. There is some evidence that this system contributes to cellular fibrinolysis. In animal models of E. coli-induced sepsis where there is substantial activation of the kallikrein/kinin system, there is associated hypotension but little evidence for DIC. Alternatively, in the same animal models where the hypotensive effect of activation of the kallikrein/kinin system is blocked, persistent evidence for DIC can be documented. These data indicate that activation of the kallikrein/kinin system is not associated with the mechanisms that result in factor VII activation and complexation with tissue factor. Thus the kallikrein/kinin system is not a direct activator of DIC, but a direct modifier of hemodynamic stability arising independently of the coagulation activation initiator.
Disseminated intravascular coagulation (DIC) is a clinicopathologic syndrome of activated coagulation that manifests itself with either excessive bleeding or thrombosis. Patients with DIC have a loss in the balance between clot formation and clot lysis. Biochemically, DIC can be explained as either excessive plasmin formation resulting in a hemorrhagic state or excessive thrombin formation resulting in thrombosis. Thus contributing mechanisms to thrombin or plasmin formation may be additional factors in the genesis of DIC. The so-called plasma "contact system of coagulation" consists of three proteins, factor XII (FXII) , prekallikrein (PK), and high molecular weight kininogen (HK). When first recognized, these proteins were believed to contribute to thrombin formation because plasma deficiencies in each of these proteins are associated with a prolonged activated partial thromboplastin time (APTT), a common assay of the plasma coagulation system.1-3 Further, deficiencies of FXII and HK are associated with reduced in vitro assays for fibrinolysis.3,4 However, clinical observations show that deficiencies of each of the proteins of the contact system are not associated with bleeding. Previous interpretations of the contributions of the contact proteins in coagulation reactions confused the results of in vitro assays with physiologic processes. There is no real role of these proteins in the generation of thrombin. Thus, it would serve this field to eliminate the name "contact system of coagulation" and refer to it as the plasma kallikrein/kinin system. This review aims to present three things: first, it will present a concise view of the clinicopathologic syndrome that constitutes DIC. Second, it will present a revised view of the plasma kallikrein/kinin (contact) system and what is its contribution(s), if any, to thrombin and plasmin formation. Last, it will critically present how the kallikrein/kinin system participates in the pathogenesis and pathophysiology of sepsis and its relation to DIC.
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