Thrombin circulating levels

Oj-antitrypsin is a nonspecific serine protease inhibitor with a broad spectrum of inhibitor activities. It is present in plasma at the highest concentration of any other serine protease inhibitor. While the protein has not been identified as a major inhibitor of the enzymes involved in coagulation and fibrinolysis, it is known to inactivate thrombin, plasmin, kallikrein, and Factor Xla. A deficiency in the circulating levels of this inhibitor has been strongly associated with the development of pulmonary disease. Several manual and automated synthetic substrate procedures for Oj-antitrypsin have been published using the first-generation substrate, BAPNA (M6). 

Levels of Circulating Thrombin Must Be Carefully Controlled or Clots May Form... 

On the neutrophil, the major selectin expressed is L-selectin. This molecule is constitutively expressed on mature neutrophils but may be expressed at low levels (50% of adult) in neonates. Stimulation of endothelial cells with thrombin, histamine, IL-1 and some other agents induces neutrophils (and other leukocytes) to leave the circulation and adhere to the endothelium. They do this by rolling onto the surface of the endothelium, to which they attach via P-selectin translocated from storage sites in Weibel-Palade bodies to the surface of the endothelium upon activation. The expression of P-selectin is short-lived and is replaced on the endothelial surface by E-selectin (whose expression is also regulated by some cytokines), which continues the endothelial-leukocyte interaction. 

Antibodies directed against (32 -GPI further enrich the protein on the cell surface but these promote a p38 Map-kinase signalling cascade which results in increased expression of tissue factor (TF) and reduced expression of thrombomodulin on the surface of cells. TF is a major initiator of coagulation and increased levels of TF expression have been measured on endothelial cells treated with anti-phospholipid antibodies and on monocytes both ex vivo and in vivo (Yasuda et al., 2005 Lopez-lira et al., 2005, Lopez-Pedrera et al., 2006). Thrombomodulin is a potent anti-coagulant protein which limits activation of thrombin, so the net result of circulating anti-phospholipid antibodies is to usurp the anti-coagulative, protective mechanism and initiate a pro-coagulation cascade. 

Enzyme assays employed in the diagnosis of diseases are one of the most frequently used clinical laboratory procedures. The most commonly used body fluid for this purpose is serum, the fluid that appears after the blood has clotted. The liquid portion of unclotted blood is called plasma. Serum is used for many enzyme assays because the preparation of plasma requires addition of anticoagulants (e.g., chelating agents) that interfere with some assays. Enzymes in circulating plasma are either plasma-specific or nonplasma-specific. Plasma-specific enzymes are normally present in plasma, perform their primary function in blood, and have levels of activity that are usually higher in plasma than in tissue cells. Examples are those enzymes involved in blood clotting (e.g., thrombin), fibrinolysis (e.g., plas-min), and complement activation, as well as cholinesterase... 

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