Antithrombin in

Cushman M, Psaty BM, Meilahn EN, Dobs AS, Kuller LH. Post-menopausal hormone therapy and concentrations of protein C and antithrombin in elderly women. Br J Haematol 2001 114(l) 162-8. 

Heparin cofactor II is a second plasma SERPIN which has resemblance to antithrombin in that it is activatable by glycosaminoglycan binding. This protein has also been called antithrombin BM, dermatan sulfate cofactor, and human leuserpin 2 (88). The existence of this second inhibitor and heparin cofactor was first shown by Briginshaw in 1974 (89). Whereas antithrombin is observed to have progressive antithrombin activity and to also inhibit factor Xa, the second... 

Heparin is a glycosaminoglycan extracted from animal tissues (porcine mucosa, beef lung, etc.). It is a mixture of molecules having a mean molecular weight of 15,000 Da. A pentasaccharide sequence found in approximately one third of the molecules binds to antithrombin in mammalian blood, enhancing its inhibitory effects on the enzymes thrombin, factor Xa, factor Vila, and factor IXa. The reaction is reversible, heparin being released after the antithrombin molecule binds to the procoagulant enzymes. Heparin binds to platelets, platelet factor-4 (which neutralizes it), histidine-rich GP vWp and a number of other proteins. Its half-life is about one hour in the circulation (18). Antibodies to heparin... 

C3. Chang, J.-Y., Antithrombin. In Human Protein Data (A. Haeberli, ed.). VCH Verlagsge-sellschaft mbH, Weinheim, 1992. 

Serpins were first identified as a set of proteins able to inhibit proteases. The name serpin is derived from this activity serine protease inhibitors . Heparin is a mixture of polysaccharides that bind to antithrombin in, inducing an allosteric change that greatly enhances its inhibition of thrombin synthesis. Some surgical patients, especially those receiving hip or heart valve replacements and those at risk of ischemic stroke (clots in the brain), are given heparin. 

Resistance to heparin. Patients with antithrombin deficiency require large doses of heparin therapy for anticoagulant effect. (The action of heparin is dependent on the presence of antithrombin in the plasma.)... 

Becker RC, Corrao JM, BoviU EG, Gore JM, Baker SP, Miller ML, Lucas FV, Alpert JA. Intravenous nitroglycerin-induced heparin resistance a quahtative antithrombin in abnormality Am Heart J 1990 119(6) 1254-61. 

Indirect antithrombins. The action of heparin is complex, and it is sometimes referred to as an indirect-acting antithrombin, in as much as it works indirectly to inhibit the action of thrombin in the coagulation cascade. Dicoumarin anticoagulants, most notably warfarin, also act in an indirect... 

Antithrombin, in presence of low molecular weight heparin, produces anticoagulation by inhibition of factor Xa. Enoxaparin causes less inactivation of thrombin, inhibition of platelets, and bleeding than standard heparin. Does not significantly influence bleeding time, prothrombin time (PT), activated partial thromboplastin time (APTT). 

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]. 

Konkle BA, Bauer KA, Weinstein R, et al. Use of recombinant human antithrombin in patients with congenital antithrombin deficiency undergoing surgical procedures. Transfusion, 2003 43(3) 390-394. 

Full-dose fibrinolysis without a glycoprotein Ilb/IIIa inhibitor but with a conservative dosing scheme of an antithrombin in patients at increased risk of bleeding. The full dose of a fibrinolytic in those above the age of 75 will likely need to be reduced, perhaps by as much as 25%. 

When blood is lost or clotting is initiated in some other way, a complex cascade of biochemical reactions is set in motion, which ends in the formation of a network or clot of insoluble protein threads enmeshing the blood cells. These threads are produced by the polymerisation of the molecules of fibrinogen (a soluble protein present in the plasma) into threads of insoluble fibrin. The penultimate step in the chain of reactions requires the presence of an enzyme, thrombin, which is produced from its precursor prothrombin, already present in the plasma. This is initiated by factor lit (tissue thromboplastin), and subsequently involves various factors including activated factor Vn, DC, X, XI and XII, and is inhibited by antithrombin in. Platelets are also involved in the coagulation process. Fibrinolysis is the mechanism of dissolution of fibrin clots, which can be promoted with thrombolytics. For further information on platelet aggregation and clot dissolution, see Antiplatelet drugs and thrombolytics , (p.697). 

Patients with a bleeding disorder including hemophilia, von WiUebrand disease, various factor deficiencies, disseminated intravascular coagulation (DIG), idiopathic thrombocytopenia purpura (ITP), antithrombin in deficiency, or protein C or S deficiency. 

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