Heparin is also used in the setting of acute myocardial infarction heart attack and unstable angina and in prophylaxis of venous thrombosis during andor after surgery. Unfractionated heparin ufh acts as an anticoagulant by forming a complex with antithrombin. Heparin also known as heparin sodium is an anticoagulant, or blood thinner. Lmwh also directly inhibits thrombin as it is a heterogenous mixture of molecules, some containing enough polysaccharide sequence, but this effect is much less than that of unfractionated heparin. The blood coagulation system is composed of various steps and heparin acts at multiple sites in this process.
Heparin is not absorbed through the gi tract, so it must be given parenterally. Heparin acts indirectly at multiple sites in both the intrinsic and extrinsic blood clotting systems to potentiate the inhibitory action of antithrombin iii heparin cofactor on several activated coagulation factors, including thrombin factor iia and factors ixa, xa, xia, and xiia, by forming a complex with and. Heparin comes in liquid form and is usually injected into a vein, under the skin, or by way of an intravenous catheter. In this study, a heparinsnac capsule formulation, unfractionated heparin ufhsnac soft gelatin capsules, was used to accomplish the oral delivery of ufh. Antithrombin inhibits coagulation proteases by forming equimolar, stable complexes with the enzymes. Binds to antithrombin at and augments the anticoagulant potential. Heparin injections may be given to patients before and after cardiac surgery. Our bodies have ways of keeping itself in balance or homeostasis. The 200708 heparin scandal caused more than 80 deaths in the u. 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. Mechanism of action and pharmacology of unfractionated heparin. Specifically it is also used in the treatment of heart attacks and unstable angina. Because blood thinners make it harder for blood to clot, doctors use them to treat and prevent blood clots in veins, arteries, and lungs. Start iv heparin without a bolus dose infusion rate depends on the indication 1 to 2 hours before the next dose of lowmolecularweight heparin lmwh or fondaparinux would have been due dager 2018.
Its molecular weight ranges from 500030,000 daltons. This seems like a second niche for iowa heparin production. Other uses include inside test tubes and kidney dialysis machines. In its natural unfractionated state, heparin exists as a heterogeneous mixture of oligosaccharides composed of alternating chains of dglucosamine and uronic acid. Heparin uses, heparin mechanism of action, heparin dosage. Heparin is an anticoagulant blood thinner that prevents the formation of blood clots. The lyases cleave heparinhs by a beta elimination mechanism. Heparin is administered in low doses when used for primary prophylaxis and high doses when used therapeutically to prevent recurrent thrombosis. Although the glass surface of the test tube acts as an activator of factor xii, the heparin doses used for cardiac surgery prolong the wbct to such a profound. This heparin is marketed in jordan and saudi arabia, where muslim preferences are for nonporcine sources. Home arteriosclerosis, thrombosis, and vascular biology vol. Baseline labs such as ptt should not be used for infusion rate adjustments per nomogram.
Protamine sulphate is the commonly used heparin antagonist. We have purified antithrombin4 from human plasma by a. The formation of these complexes involves the attack by the enzyme of a specific argser bond in the. Charles from the connaught laboratories, university of toronto, toronto, canada received for publication, july 15, 1933 in view of the fact that we had succeeded in preparing a quantity. Teva, a israeli pharmaceutical producer of generic drugs, supplies kosher heparin to israel. By forming ternary complexes heparinantithrombinthrombin. Heparin is also used before surgery to reduce the risk of blood clots 3. Intravenous high intensity heparin nomogram venous. Heparin binds to antithrombin, which changes the shape of antithrombin. Approximately onethird of heparin molecules contain a unique pentasaccharide sequence with highaffinity binding to atiii. 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.
Fondaxaparinux is used for the prevention and treatment of deep vein. Heparin increases the inhibitory action of antithrombin in thousands of times. She has obtained the heparin from the medication dispensing system and is preparing to mix the heparin in iv. Heparin powerpoint presentation cme at pharmacology corner. An allosteric mechanism, in which heparin provokes conformational changes in antithrombin that increases its ability to inhibit some of the coagulation factors, 2. Heparin, also known as unfractionated heparin ufh, is a medication and naturally occurring. Transitioning from a therapeutic dose of subq lowmolecularweight heparin or subq fondaparinux to a therapeutic dose of iv heparin. Mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. A detailed overview of market dynamics, including the drivers, restraints, and opportunities of the heparin market, along with porters analysis, major brand analysis, and market strategies adopted by top players of the global heparin market, has been provided in this report. Pharmacodynamics of intravenous and subcutaneous tinzaparin. They have been shown to be at least as effective and safe as unfractionated heparin and have replaced the latter in many indications.
Intravenous high intensity heparin nomogram venous thromboembolism dvt pe hch2282 eff. Heparin overview and issues bussey and francis factor 4. However, with increasing understanding of the mechanisms of action of lmwhs, it has. Heparin contamination, heparin drip, heparin injections. Heparin given sc has a much slower onset of action. Heparin is used to decrease the clotting ability of a patients blood, and is widely referred to as a blood thinner. Heparin is a sulfated polysaccharide with a molecular weight range of 3000 to 30 000 da mean, 15 000 da.
Confirm the selection of the correct formulation and strength prior to administration of the drug. Heparin catalysis of clotting proteinase inactivation occurs most efficiently through the reaction of the proteinase with the antithrombinheparin complex. Heparin prevents blood clots by blocking the action of two of the 12 clotpromoting proteins in blood factors x and ii whose action is necessary for blood to clot. An understanding of the molecular mechanisms underlying the antithrombotic action has allowed the dissociation of the specific anticoagulant effects of heparin from other nonspecific interactions with plasma proteins, platelets and the vascular endothelium, which contribute to certain undesirable features of heparin anticoagulant therapy. The 2nd workshop on the characterisation of heparin products was the opportunity to debate on the current situation and reactions of the different regulatory organisations and industries, and consider a harmonised approach between pharmacopoeias and licensing authorities to best handle this health problem. A natural inhibitor of thrombin in the body is called antithrombin. Ppt discussing chemistry, mechanism of action, classification,pharmacokinetics and clinical uses of heparin. Heparin does not cross the placental barrier warfarin does, so it is the anticoagulant of choice during pregnancy. It produces its major anticoagulant effect by inactivating thrombin and activated factor x factor xa through an antithrombin atdependent mechanism.
Geriatric patients at least one manufacturer reports a greater risk of hemorrhage in women older than age 60. Heparin is a naturally occurring glycosaminoglycan with a negative ionic charge. Karen masterson, circulator, is preparing the or for a capsular procedure where heparin will be used. Pdf on nov 1, 1995, j hirsh and others published heparin. Jackson the current understanding of how heparin produces its anticoagulant action has evolved during the last 60 years as a result of several observations which may be marked as milestones.
Heparin mechanism of action the biochemistry questions site. Lmwh lowmolecularweight heparin mi myocardial infarction pt prothrombin time tnk tenecteplase tpa tissue plasminogen activator ufh unfractionated heparin u units vte venous thromboembolism mechanism of action. Once this change occurs lmwh is freed and can bind to another antithrombin molecules. Lowmolecularweight heparins in the treatment of acute coronary. This presentation describes recent advances in knowledge of heparin action and considers how they may alter methods of monitoring heparin therapy and change notions of the surface properties of. Yet we restrict ourselves here to a discussion of the. Because of the risk of overdose, avoid heparin lock flush solutions that contain heparin sodium 100 mgml for use in neonates, especially those with a low birth weight. Since heparin also contains disulfated disaccharides it was found important to test the action of heparitinase ii upon heparin and its products formed by the action of the hepari nase the present paper reports the complete degradation of heparin to disaccharides by the joint action of a heparinase and. Stating and labeling the drugs dosage, strength, and expiration date.
Coagulation monitoring 265 undivided attention of the person performing the test for periods up to 30 minutes. It is given by injection into a vein or under the skin. Pharmacokinetics and pharmacodynamics of oral heparin. A number of new anticoagulants, already developed or under development, target specific steps in the process, inhibiting a single coagulation factor or mimicking natural coagulation inhibitors. Mechanisms may include inhibition of viral enzymes or processes such as viral dna and rna polymerase, viral protein glycosylation, virus assembly, new virus particle transport, and virus release. Two major mechanisms underlie heparins potentiation of antithrombin. The efficiency of a heparin molecule in this reaction depends on the presence of a specific pentasaccharide sequence in it, and its molecular weight. In addition, heparin is used to maintain patency of intravenous indwelling catheters heparin lock, usually in low doses 10 to 100 units. Food and drug administration fda have shown that heparin sodium, usp heparin made under the new united states pharmacopeia usp monograph. The molecular basis for the anticoagulant action of heparin lies in its ability to bind to and enhance the inhibitory activity of the plasma protein antithrombin against several serine proteases of the coagulation system, most importantly factors iia thrombin, xa and ixa. The binding of heparin to platelet factor 4 is thought to be responsible for one of the most serious heparinrelated complications, heparininduced thrombocytopenia hit. Discovery of heparin chemical structure of heparin mechanism of.
The therapeutic roles of heparinbased drugs, including unfractionated heparin ufh, low molecular weight heparin lmwh 3, and synthetic heparins 4 are discussed. As a medication it is used as an anticoagulant blood thinner. Classical anticoagulants, including heparin and vitamin k antagonists, typically target multiple coagulation steps. The anticoagulant and antithrombotic mechanisms of heparin. Despite the development of newer anticoagulants, unfractionated heparin remains an indispensible agent in the treatment of thrombotic disorders. It seems that bovine heparin is produced from the lungs of cattle. Mechanism of action of high molecular weight heparin, low molecular weight heparin and fondaparinaux. Antithrombin iii heparin cofactor is known to inhibit thrombin1 and factor xa activated factor x. The basic mechanism of heparins action is best described as. Mechanisms of action heparin binds to and potentiates the actions of antithrombin at to inactivate factor xa and prevent the conversion of. Gosselin, cls robert raschke, md, ms tim vanderveen, pharmd, ms. Mechanism of action of heparin unfractionated heparin, low molecular weight heparin, fondaparinux duration.
Mechanism of action and pharmacology of unfractionated. Namely, the binding of heparin to thrombin can induce a conformational change of the enzyme resulting in an accelerated inactivation by antithrombin. Heparin is able to bind to antithrombin because of its structure as one of the most negatively charged molecules in the body. Mechanism of action of heparin through thrombin on blood. The mode of action of heparins in vitro and in vivo springerlink.
Since recently even the importance of antithrombinheparin inter action was doubted 4, this new theory about the effect of heparin on the thrombin antithrombin reaction seems to be reasonable. Its molecular weight ranges from 500030,000 daltons with an average weight of 15,000 daltons. Earlier studies demonstrated that after the oral administration of heparinsnac, antifactor xaantifactor iia activities are achieved in. The use and limitations of unfractionated heparin amar krishnaswamy, md, a. Haemostasis occurs through the rapid formation of an impermeable platelet and fibrin plug haemostatic thrombus. Heparin, also known as unfractionated heparin ufh, is a medication and naturally occurring glycosaminoglycan. Heparin exerts its major effect via antithrombin, converting. Serious side effects include heparininduced thrombocytopenia. The antithrombotic action of a heparin is not necessarily confined to its effects on the clotting mechanism. Antithrombin iii atiii mediated selective inhibition xa and to a lesser extent iia.
We know that heparin interferes with the blood clotting process, but how does it do so. In the absence of heparin, protamine sulphate can act as a weak anticoagulant itself. Heparin is used to treat and prevent blood clots in the veins, arteries, or lung. Laboratory studies performed at the request of the u. Heparin exerts its anticoagulant action by accelerating the activity of antithrombin iii atiii to inactivate thrombin.
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