HEPARIN
Heparin is an anticoagulant medication that prevents the formation of blood clots. The importance of heparin in the context of anesthesia and surgery includes:
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Prevention of thromboembolic events: Heparin is commonly used during surgical procedures, particularly cardiovascular surgeries, to reduce the risk of blood clots, deep vein thrombosis (DVT), and pulmonary embolism. These events can be life-threatening and may lead to significant morbidity and mortality.
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Cardiopulmonary bypass: During open-heart surgeries and other procedures requiring cardiopulmonary bypass, heparin is administered to prevent clot formation in the extracorporeal circuit, which could otherwise lead to disastrous consequences.
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Vascular procedures: Heparin is used in various vascular procedures, such as angioplasty, stenting, and vascular access placement, to prevent thrombosis and maintain blood flow through the treated vessels.
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Indwelling catheters and lines: Heparin may be used to flush intravascular catheters or lines, such as central venous catheters and arterial lines, to keep them patent and prevent clot formation.
Heparin's mechanism of action mainly involves its interaction with a plasma protein called antithrombin III (AT III), which is a natural inhibitor of several clotting factors, particularly thrombin (factor IIa) and activated factor X (factor Xa). The steps of heparin's mechanism of action are as follows:
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Heparin binds to antithrombin III: Heparin forms a complex with AT III through electrostatic interactions. This binding induces a conformational change in the AT III molecule, which significantly enhances its inhibitory activity against coagulation factors.
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Inhibition of thrombin (factor IIa) and factor Xa: The heparin-AT III complex inactivates thrombin and factor Xa by binding to their active sites, blocking their ability to participate in the coagulation cascade. Thrombin is responsible for converting fibrinogen to fibrin, which is a crucial step in clot formation. Factor Xa is a critical component in the conversion of prothrombin to thrombin. By inhibiting both thrombin and factor Xa, heparin effectively prevents clot formation and propagation.
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Inhibition of other coagulation factors: Although heparin's primary targets are thrombin and factor Xa, the heparin-AT III complex can also inhibit other coagulation factors, such as factor IXa, factor XIa, and factor XIIa, to a lesser extent.
It is important to note that heparin does not break down existing clots but prevents their formation and growth. Heparin's anticoagulant effect is measured by laboratory tests such as activated partial thromboplastin time (aPTT) or anti-factor Xa levels, which help guide dosing and ensure the appropriate level of anticoagulation is maintained.
There are two main types of heparin: unfractionated heparin (UFH) and low molecular weight heparin (LMWH). Both types share the same overall mechanism of action, but LMWH has a higher affinity for factor Xa and a lower affinity for thrombin compared to UFH. This results in a more predictable anticoagulant response, and LMWH does not typically require routine laboratory monitoring like UFH.
Key points about Heparin
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Unfractionated heparin is an extract of porcine intestine or bovine lung, where heparin is stored in mast cells.
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Produces anticoagulant effect by binding antithrombin III (AT).
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Enhances the rate of thrombin-AT complex formation by 1,000 to 10,000 times.
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Antithrombin also inhibits factors IX, Xa, XI, and XII.
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Anticoagulation depends on the presence of adequate amounts of circulating antithrombin.
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Treatment options for heparin resistance include antithrombin concentrate or fresh frozen plasma.