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The mechanism of action of heparin is ATIII-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved.
Heparin is a sulfated polysaccharide with a molecular weight range of 3000 to 30 000 Da (mean, 15 000 Da). It produces its major anticoagulant effect by inactivating thrombin and activated factor X (factor Xa) through an antithrombin (AT)-dependent mechanism.
This activity outlines the indications, mechanism of action, dosing, important adverse effects, contraindications, monitoring, and toxicity of heparin and increases practitioners' knowledge regarding how to approach this medication and use and monitor it effectively to drive better patient outcomes.
In this chapter the mechanisms of action of heparin and LMWHs, their pharmacokinetics, anticoagulant effects, and laboratory monitoring will be reviewed. The clinical uses of heparin and LMWHs will be summarized briefly since they are discussed in detail in other chapters.
Potentiates the action of antithrombin III and thereby inactivates thrombin (as well as other coagulation factors IXa, Xa, XIa, XIIa, and plasmin) and prevents the conversion of fibrinogen to fibrin; heparin also stimulates release of lipoprotein lipase (lipoprotein lipase hydrolyzes triglycerides to glycerol and free fatty acids)
Heparin is the anticoagulant of choice when a rapid anticoagulant effect is required because its onset of action is immediate when administered by intravenous injection. Heparin is administered in low doses when used for primary prophylaxis and high doses when used therapeutically to prevent recurrent thrombosis.
These 2 fundamental mechanisms of thrombogenesis are closely linked in vivo, because thrombin, a key clotting enzyme generated by blood coagulation, is a potent platelet activator, and activated platelets augment the coagulation process.
This chapter will review the mechanisms of action of heparin and LMWHs, their pharmacokinetics, anticoagulant effects, side effects, andlaboratory monitoring. The clinical uses of heparin and LMWHs and theresults of clinical trials will also be discussed, although moredetails appear in other chapters.
Unfractionated Heparin (UFH): These include heparin, make complexes with antithrombin 3, and inactivates various clotting factors. Its onset of action is rapid, has a short half-life, and can be monitored using activated partial thromboplastin (aPTT), activated clotting time, and anti-factor 10a activity.
The anticoagulant effect of heparin, a sulfated glycosaminoglycan produced by mast cells, requires the participation of the plasma protease inhibitor antithrombin, also called heparin cofactor. Antithrombin inhibits coagulation proteases by forming equimolar, stable complexes with the enzymes.