Procoagulants

Coagulation Factors II, III, VII, IX, X, XI, and Xlla fragments, thrombin, and plasmin are classified as serine proteases because each possesses a serine residue with neighboring histidine and asparagine residues at its enzymatically active site (Table 3). Factors II, VII, IX, and X, Protein C, Protein S, and Protein Z are dependent on the presence of vitamin K [84-80-0] for their formation as biologically functionally active procoagulant glycoproteins. 

Factor IX. This factor is dependent on the presence of vitamin K for its activity as a biologicaUy functional procoagulant glycoprotein. Factor IX is converted to its active form by XIa in the classic scheme of the intrinsic pathway. However, it can also be activated via interaction with Factor Xa or the complex Factor III plus Factor VII in the presence of calcium. 

As with UC, the immune activation seen in CD involves the release of many proinflammatory cytokines. Cytokines thought to play major roles in CD are derived from T-helper type 1 cells and include interferon-y, TNF-a, and IL-1, IL-6, and IL-12. TNF-a is a major contributor to the inflammatory process seen in CD. Its physiologic effects include activation of macrophages, procoagulant effects in the vascular endothelium, and increases in production of matrix metallo-proteinases in mucosal cells.9,15 Excessive production of both... 

The inflammatory process in sepsis is linked to the coagulation system. Pro-inflammatory mediators maybe procoagulant and antifibrinolytic, whereas anti-inflammatory mediators may be fibrinolytic. A key factor in the inflammation of sepsis is activated protein C, which enhances fibrinolysis and inhibits inflammation. Protein C levels are decreased in septic patients. 

Cryoprecipitate Component of blood obtained by freezing and thawing plasma that is rich in clotting factors. One unit of cryoprecipitate derived from a unit of whole blood contains a volume of 10 to 20 mL, 80 to 100 units of factor VIII which consists of both the procoagulant activity and the von Willebrand factor, 150 to 250 mg of fibrinogen, 50 to 100 units of factor XIII, and 50 to 60 mg of fibronectin. 

IL-1 (17.5) Monocyte/macrophage, lymphocyte, neutrophil, endothelium, fibroblast keratinocyte Activation of T cells, B cells, natural killer cells, osteoblasts, and endothelium. Induces fever, sleep, anorexia, ACTH release, hepatic acute phase protein synthesis and HSPs. Leads to myocardial depression, hypercoagulability, hypotension/sbock, and death. Simulates production of TNF, IL-6, and IL-8 and stress hormone release. Suppression of cytochrome P-450, thyro-globulin, and lipoprotein synthesis. Procoagulant activity. Antiviral activity. 

Interleukin-10 (IL-10) affects antigen presentation capacity but also interferes with many other functions of monocytes and macrophages (Table 2) (F8). In vitro, IL-10 is a potent inhibitor of cytokine production, including production of TNF, IL-1, IL-6, and IL-8 by LPS-activated monocytes/macrophages (F8). It also inhibits tissue factor-dependent procoagulant activity induced by LPS in human... 

The procoagulant factors produced by endothelial cells are the coagulation factors von Willebrand factor (WF), F-V, F-VIII, tissue factor (TF), and plasminogen activator inhibitor (PAI), which blocks the activators u-PA and t-PA and counteracts fibrinolysis (G21, FI6). It has been shown that under the influence of complement activation (C9), in response to endotoxin in vitro (C24), in experimental E. coli sepsis in baboons (D30), and after stimulation with TNF (Al, N6), endothelial cells up-regulate the expression of TF, down-regulate TM and inhibit the production of t-PA and PAF. Thus, the balance may shift in the procoagulant direction with a large excess of PAI-1. 

M2. Maier, R. V., Hahnel, G. B., and Fletcher, J. R Platelet-activating factor augments tumor necrosis factor and procoagulant activity. J. Surg. Res. 52,258-264 (1992). 

P20. Pradier, O., Gerard, C., Delvaux, A., Lybin, M., Abramowicz, D., Capel, P., Velu, T., and Goldman, M Interleukin-10 inhibits the induction of monocyte procoagulant activity by bacterial lipopoysaccharide. Eur. J. Immunol. 23,2700-2703 (1993). 

Leung L Saigo K., Grant D. Heparin binds to human monocytes and modulates their procoagulant activities and secretory phenotypes. Effect of histidine-rich glycoprotein. Blood 1989 73, 177-84. 

Gorbet, M. B., and Sefton, M. V., Expression of procoagulant activities on leukocytes following contact with polystyrene and PEG grafted polystyrene beads. J. Lab. Clin. Med. 137, 345-355 (2001). 

Proinflammatory mechanisms in sepsis are also procoagulant and antifibrinolytic. Levels of activated protein C, a fibrinolytic and antiinflammatory substance, are decreased in sepsis. 

The plasma proteinase, thrombin, a procoagulant enzyme with effects on platelets, endothelial cells and smooth muscle, has been shown to stimulate bone-marrow-derived murine mast cells to release histamine and jS-hexos-aminidase [135]. This secretory response is rapid, reaching a maximum in 1-2 min, and dose-dependent, beginning at about 0.1 U of thrombin and plateauing at 0.5 U thrombin. 

Products produced from solid tissue sources (excluding procoagulants, venoms, blood products, etc.)... 

Human blood or human blood-derived products, including placental blood-derived products, animal-derived procoagulant products and animal- or cell culture-derived hemoglobin-based products intended to act as red blood cell... 

Other actions of proteases that may directly or indirectly affect the production of metastasis include their ability to stimulate cell migration, act as procoagulants, digest fibrin surrounding cancers, enhance cancer cell-platelet ag-... 

Thiagarajan, P. and Tait J.F., 1990, Binding of annexin V/placental anticoagulant protein 1 to platelets. Evidence for phosphatidylserine exposure in the procoagulant response of activated platelets. J. Biol. Chem., 265 17420-17423. 

MaUat, Z, Hugel, B., Ohan, J., Leseche, G., Freyssinet, J.M., and Tedgui, A., 1999, Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques a role for apoptosis in plaque thrombogenicity, Circulation 99 348-353. 

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