Heparin with antithrombin

Although the order of affinity of PF-4 for different glycosaminogly-cans, and dissociation of their complexes with salts, are typical of nonspecific, electrostatic interactions, PF-4 is not strictly a cationic protein.452 It is probable that heparin binds to clusters of basic amino acids (two lysine pairs) near the carboxyl terminal of a polypeptide chain that has an overall preponderance of acidic amino acid residues.457 High-molecular-weight heparin species can bind two PF-4 molecules, with formation of complexes 10 to 100 times as strong as those with antithrombin.217... 

The fluorescent labelling of heparin with F-D by this technique did not observably alter the biologic activity of the heparin as regards to its binding to antithrombin and catalysis of antithrombin s neutralization of activated coagulation factors. F-D labelled heparins also bound to other known heparin-binding proteins in a saturable and reversible manner, as demonstrated by the dot-blot assay technique (Figure 6). 

Based on the mixed-phase method, ACE is introduced for studying the interaction of heparin with the serine protease inhibitors, antithrombin III (ATIII) and secretory leukocyte proteinase inhibitor (SLPI) (85). An etched capillary, to which heparin has been covalently immobilized, was used in this study. This modified capillary both afforded an improvement in the separation of heparin-binding proteins and required a lower quantity of loaded protein. 

B. Thrombocytopenia is a frequent side effect association with heparin. This reduction in the level of circulating platelets increases bleeding. Purple toes are encountered during warfarin therapy. Heparin may be administered to pregnant mothers without risk to the fetus. Heparin requires antithrombin III for its anticoagulant action, but does not increase the level of this protein in the blood. 

Santos, J. C, Mesquita, J. M. F., Belmiro, C. L. R., Carolina da Silveira, . M., Viskov, C., Mourier, P. A., and Pavao, M. S. G. (2007). Isolation and characterization of a heparin with low antithrombin activity from the body of Styela plicata (Chordata-Tunicata). Distinct effects on venous and arterial models of thrombosis. Thromb. Res. 121,213-222. 

Cesaretti, M., Luppi, E., Maccari, M., and Volpi, N. (2004). Isolation and characterization of a heparin with high anticoagulant activity from the clam Tapes philippinarum. Evidence for the presence of a high content of antithrombin Ill-binding site. Glycobiology 14,1275-1284. 

The indirect thrombin inhibitors are so named because their antithrombotic effect is exerted by their interaction with antithrombin. Unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and the synthetic pentasaccharide fondaparinux bind to antithrombin and enhance its inactivation of factor Xa. UFH and to a lesser extent LMWH also enhance antithrombin s inactivation of thrombin (Ha). 

UFH binds to exosite 2, located on antithrombin, forming a ternary complex. This ternary complex is necessary for the inhibition of thrombin by antithrombin (Fig. I A, left). Conversely to thrombin inhibition, inactivation of factor Xa does not require the formation of the ternary complex. UFH inhibits thrombin and factor Xa in the same proportion (the ratio of anti-Xa/lla activity equals I) (Fig, I A, right). The interaction of the heparins (UFH and LMWH) with antithrombin is mediated by a unique pentasaccharide sequence, which is present in approximately one-third of the UFH chains (2). 

Rapid I Antithrombin III I plus heparin very slowly. The binding of heparin to antithrombin III produces a conformational change allowing the antithrombin to rapidly combine with and inhibit thrombin except that already bound to fibrin. 

Inactive factors [Note While the heparin-antithrombin III complex readily inactivates thrombin, the complex of low molecular weight heparin with... 

The complex consisting of heparin and antithrombin III neutralizes the protease activity of activated factors unlike unfrac-tionated heparin, low-molecular-weight heparin fragments or the minimal molecular subunit of heparin, fortdaparinux, inhibit only activated factor Xa when com-plexed with antithrombin III. 

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