Plasma antithrombin

Heparin is an important anticoagulant. It binds with factors IX and XI, but its most important interaction is with plasma antithrombin III (discussed in Chapter 51). Heparin can also bind specifically to lipoprotein lipase present in capillary walls, causing a release of this enzyme into the circulation. 

Plasma amine oxidase 886 Plasma antithrombin III 177 Plasma membrane 12, 379 Plasmalemma. See Plasma membrane Plasmalogens 383s, 384 Plasmids 5, 248249 ColEl 248 drug resistance 248 Plasmin 634 Plasminogen 634 Plasmodesmata 10... 

The acylated enzyme is not inactivated by the progressively acting plasma-antithrombin in spite of the prolonged incubation time, as demonstrated in our previous experiments with synthetic inhibitors, which block the active center of the enzyme [24]. 

Sowers, J. R., Tuck, M. L., and Sowers, D. K., Plasma antithrombin III and thrombin generation time correlation with hemoglobin Ai and fasting serum glucose in young diabetic women. Diabetes Care 3, 655-658 (1980). 

Mechanism of action Activates plasma antithrombin, blocks thromboplastin Inhibits the synthesis of factors II, VII, IX, and X by... 

Walker, I. D., Davidson, J. F., Yound, P., and Conkie, J. A., 1975, Effect of anabolic steroids on plasma antithrombin III, a2-iriacroglobulin and -antitrypsin levels, Thromb. Diath. Haemorrh. 34 106. 

Affinity chromatography is used in the preparation of more highly purified Factor IX concentrates (53—55) as well as in the preparation of products such as antithrombin III [9000-94-6] (56,57). Heparin [9005-49-6], a sulfated polysaccharide (58), is the ligand used most commonly in these appHcations because it possesses specific binding sites for a number of plasma proteins (59,60). 

Factor VIII, immunoglobulin, and albumin are all held as protein precipitates, the first as cryoprecipitate and the others as the Cohn fractions FI + II + III (or FII + III) and FIV + V (or FV), respectively (Table 7, Fig. 2). Similarly, Fractions FIVj + FIV can provide an intermediate product for the preparation of antithrombin III and a-1-proteinase inhibitor. This abiUty to reduce plasma to a number of compact, stable, intermediate products, together with the bacteriacidal properties of cold-ethanol, are the principal reasons these methods are stiU used industrially. 

Alpha-1-proteinase inhibitor and antithrombin III are used to treat people with hereditary deficiencies of these proteins. Both can be recovered from Cohn Fraction IV (Table 7) using ion-exchange chromatography (52) and affinity chromatography (197), respectively. Some manufacturers recover antithrombin III directiy from the plasma stream by affinity adsorption (56,198,199). 

Four naturally occurring thrombin inhibitors exist in normal plasma. The most important is antithrombin III (often called simply antithrombin), which contributes approximately 75% of the antithrombin activity. Antithrombin III can also inhibit the activities of factors IXa, Xa, XIa, Xlla, and Vila complexed with tissue factor. a2-Macroglobulin contributes most of the remainder of the antithrombin activity, with heparin cofactor II and aj-antitrypsin acting as minor inhibitors under physiologic conditions. 

With respect to both the coagulation and fibrinolytic cascade systems, in 28 patients who developed septic shock a relation was found between lowered plasma levels of F-XII and antithrombin III and elevated levels of PAI-1 and thrombin-antithrombin III complexes at the diagnosis of sepsis and the severity of disease, expressed according to the APACHE II scoring system (L7). Nevertheless, administration of inhibitors of coagulation or enhancement of fibrinolysis did not improve the outcome in patients with sepsis (B35). 

Heparin is a carbohydrate-based (glycosaminoglycan) anticoagulant associated with many tissues, but mainly found stored intracellularly as granules in mast cells that line the endothelium of blood vessels. Upon release into the bloodstream, heparin binds to and thereby activates an additional plasma protein, namely antithrombin. The heparin-antithrombin complex then binds a number of activated clotting factors (including Ha, IXa, Xa, XIa and Xlla), thereby inactivating them. The heparin now disassociates from the complex and combines with another antithrombin molecule, thereby initiating another turn of this inhibitory cycle. 

Antithrombin, already mentioned in the context of heparin, is the most abundantly occurring natural inhibitor of coagulation. It is a single-chain 432 amino acid glycoprotein displaying four oligosaccharide side chains and an approximate molecular mass of 58 kDa. It is present in plasma at concentrations of 150 pig ml 1 and is a potent inhibitor of thrombin (factor Ha), as well as of factors IXa and Xa. It inhibits thrombin by binding directly to it in a 1 1 stoichiometric complex. 

Plasma-derived antithrombin concentrates have been used medically since the 1980s for the treatment of hereditary and acquired antithrombin deficiency. Hereditary (genetic) deficiency is characterized by the presence of little/no native antithrombin activity in plasma and results in an increased risk of inappropriate blood clot/emboli formation. Acquired antithrombin deficiency can be induced by drugs (e.g. heparin and oestrogens), liver disease (decreased antithrombin... 

Antithrombin El and Factor IX from human plasma In-process control Affinity (Heparin) [71]... 

Integral plasma membrane proteins from a human lung cancer cell line (62 prenylated proteins and 45 Ras family proteins) urinary proteins AGP-derived glycoproteins major and minor populated isoforms of antithrombin regulatory lipids in breath condensate ... 

Plematl, A., Demelbauer, U. M., Josic, D., and Rizzi, A., Determination of the site-specific and isoform-specific glycosylation in human plasma-derived antithrombin by lEF and capillary HPLC-ESl-MS/MS, Proteomics 5(15), 4025-4033, 2005. 

Determination of acute-phase proteins (CRP, orosomucoid, haptoglobin, transferrin, prealbumin), immunoglobulins (IgA, IgG, IgM), compressive markers (albumin, fibrinogen), markers of tissue destruction (Apo A-I, A-II, Apo B), components of complement (C3, C4), proteinase inhibitors (antithrombin HI, a -antitrypsin). The measurement was performed simultaneously in CSF and in serum (plasma) by a laser nephelometric method. The functional state of the blood-CSF barrier was evaluated numerically with the help of the quotient Q = Albcsp/s and also by the intrathecal synthesis of immunoglobulins according to Reiber s formula and for each class—IgG, IgM, IgA. 

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