Derangements of Coagulation and Fibrinolysis in Critically III Patients with Sepsis and Septic Shock

Abstract

In patients with sepsis and septic shock, both coagulation and fibrinolysis are activated frequently leading to the syndrome of diffuse intravascular coagulation (DIC). The different mechanisms leading to abnormalities in coagulation and fibrinolysis are discussed in detail. The coagulation and fibrinolytic system appear to be influenced by the septic process largely independently, leading to a procoagulant imbalance between these systems. Coagulation is initiated by mediator-induced expression of tissue factor and is associated with consumption of the natural coagulation inhibitors antithrombin III, protein C, and protein S. As a result, high plasma levels of thrombin-antithrombin complex (TAT) can be found. The effects on fibrinolysis are dominated by (highly) increased levels of plasminogen activator inhibitor type 1 (PAI-1), leading to inadequate fibrinolysis. Although levels of plasminogen activator antigen are increased, its activity is almost completely inhibited by PAI-1. The resulting effects predispose to a procoagulant state, with widespread fibrin deposition, which may be an important mechanism contributing to multiple organ failure. A thorough understanding of the pathophysiological mechanisms underlying the DIC-syndrome is a prerequisite for a rational approach and future therapy for this severe complication of sepsis.

Monocytes regulate systemic coagulation and inflammation in abdominal sepsis

“…2, A-D). TAT complexes formed after neutralization of thrombin by antithrombin III have been used as a surrogate marker for thrombin generation (39). In the present study, we observed that CLP markedly increased plasma levels of TAT complexes and that the administration of clodronate significantly reduced CLP-induced TAT complex levels in plasma by 54% (Fig.…”

Modulation of Serpin Reaction through Stabilization of Transient Intermediate by Ligands Bound to α-Helix F

“…High levels of PAI-1 inhibit the fibrinolytic system by preventing the formation of plasmin from plasminogen and promote thrombosis (6,7). An elevated concentration of PAI-1 correlates with an increased rate of ischemic arterial disease (8) as follows: atherosclerosis, angina pectoris (9 -14), and myocardial infarction (15)(16)(17)(18)(19)(20)(21)(22), as well as with deep vein thrombosis and disseminated intravascular coagulation (23)(24)(25). Because complete inactivation of PAI-1 is not lifethreatening (26 -28), the development of new approaches to the therapeutic neutralization of PAI-1 is a subject of many studies (for review see Refs.…”

The role of endothelin-1 and new therapeutic approaches in sepsis and septic shock

“…Sepsis patojenezinde enflamasyon gelişimi, kompleman sistem etkinleşmesi ve koagülasyon gelişmesi ve fibrinolizde bozukluklar yer almakta olup, sitokinler, proteazlar, lipit mediyatörler, gaz yapısındaki maddeler ve vazoaktif peptitler önemli rol oynamaktadır (Şekil 4) (20)(21)(22)(23)(24). Toksinler dolaşıma karıştığı zaman makrofajları etkinleştirerek MAPK ve NF-κB aracılıklı interlökin (IL)-1, IL-6, IL-8 ve tümor nekrozlaştırıcı faktör-α (TNF-α) gibi birçok enflamatuvar sitokin salıverilmesine yol açmaktadır.…”