Plasma Thrombin Activatable Fibrinolysis Inhibitor and Tissue Factor Pathway Inhibitor Changes Following Sepsis

Abstract

Sepsis-induced systemic inflammation results in coagulation abnormalities that may be different in gram-positive and gram-negative infections. We used ciprofloxacin to induce a predominantly gram-positive Enterococcus faecalis polymicrobial sepsis in rats. Ciprofloxacin-untreated rats exhibited a predominantly gram-negative polymicrobial sepsis. Rats were subjected to 30% body surface area burn (B), cecal ligation puncture (CLP) with a 22-gauge needle, and B + CLP. Ciprofloxacin-treated B + CLP rats showed a significant decrease in plasma thrombin activatable fibrinolysis inhibitor (TAFI) levels compared with sham rats. However, plasma tissue factor pathway inhibitor (TFPI) levels decreased significantly in B, CLP, and B + CLP groups compared with sham rats. The ciprofloxacin-untreated group showed a significant decrease in plasma TAFI levels in CLP and B + CLP and plasma TFPI levels decreased in all 3 groups compared with sham rats. Histological changes in the liver and kidney included vascular congestion and parenchyma bleed following B + CLP in ciprofloxacin-untreated rats. These results suggest that plasma TAFI and TFPI levels differ depending on the type of bacteria involved in the septic process.

Blood coagulation and fibrinolysis in patients with acromegaly: increased plasminogen activator inhibitor-1 (PAI-1), decreased tissue factor pathway inhibitor (TFPI), and an inverse correlation between growth hormone and TFPI

“…The normal range for serum GH was \5 ng/ml. The normal range for IGF-1 was age-, but not sex-adjusted (21)(22)(23)(24)(25) Serum TC was measured using a cholesterol oxidase enzymatic method; triglycerides (TG), by a glycerol oxidase enzymatic method; HDL-C, by a cholesterol oxidase enzymatic method in supernatant after precipitation with phosphotungstic acid-MgCl 2 . These routine analyses were carried out by autoanalyzer (Technicon AXON).…”

“…Increased TAFI levels have been associated with several thrombotic conditions such as venous thromboembolism [20,21] and ischemic stroke [22]. Tissue factor pathway inhibitor (TFPI) is secreted by the endothelium and stored in platelets [23]. TFPI binds directly and inhibits the earliest activation steps in the extrinsic pathway by binding tissue factor (TF)/factor VIIa and forming an inactive quaternary complex with factor Xa, the first step of the common pathway [24].…”

Increased thrombin-activatable fibrinolysis inhibitor and decreased tissue factor pathway inhibitor in patients with hyperthyroidism

“…Increased TAFI levels have been associated with several thrombotic conditions like venous thromboembolism [17,18] and ischemic stroke [19,20]. TFPI is secreted by the endothelium and stored in platelets [21]. TFPI binds directly and inhibits the earliest steps in extrinsic pathway activation by binding factor Xa (which involved in the activation of prothrombin to thrombin) and tissue factor/ factor VIIa complexes in an inactive quaternary complex [22].…”

Increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels in patients with primary hyperparathyroidism

“…TFPI, a potent anticoagulant protein, inhibits the activity of the TF-factor VIIa catalytic complex that is involved in activation of IX to IXa and also directly inhibits FXa that activates blood coagulation (29,42). Both endothelial cells and platelets produce TFPI (42).…”

“…Increased TAFI levels have been associated with several thrombotic conditions like venous thromboembolism (25,26) and ischemic stroke (27,28). Tissue factor pathway inhibitor (TFPI) is secreted by the endothelium and stored in platelets (29). TFPI binds directly and inhibits the earliest steps in extrinsic pathway activation by binding factor Xa (which involved in the activation of prothrombin to thrombin) and tissue factor (TF)/factor VIIa complexes in an inactive quaternary complex (30).…”