Heparin

UNDER REVIEW (September 2016)

Mechanism of Action:

Heparin is an acidic mucopolysaccharide found especially in lung and liver tissue and having the ability to prevent the clotting of blood, used in the treatment of thrombosis. Heparin works by potentiating the action of antithrombin III, as it is similar to the heparan sulphate proteoglycans which are naturally present on the cell membrane of the endothelium. Because antithrombin III inactivates many coagulation proteins (especially those of the intrinsic cascade), the process of coagulation will slow down.

Lecture and CAL materials:

• Lecture: Venous Thrombo-Embolism: Pathogenesis, prevention and treatment
• CAL: Haemostasis

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Drug specifics

Alternative drug name	Herparin Sodium
Effects	Anticoagulant. A complex organic acid that is found especially in lung and liver tissue, has a mucopolysaccharide as its active constituent, prevents platelet agglutination and blood clotting, and is used in the form of its sodium salt in the treatment of thrombosis. It prevents the formation of clots or extension of existing clots within the blood. While heparin does not break down clots that have already formed, it allows the body's natural clot lysis mechanisms to work normally to break down clots that have already formed. This effect is used to good clinical effect as prophylaxis against or treatment for deep vein thrombosis and pulmonary embolus. Heparin is also used in the maintenance of extracorporeal circuits in cardiopulmonary bypass and haemodialysis.
Adverse actions	A serious side effect of heparin is heparin induced thrombocytopenia (HIT syndrome). HIT is caused by an immunological reaction that makes platelets form clots within the blood vessels, thereby using up coagulation factors. Formation of platelet clots can lead to thrombosis, while the loss of coagulation factors and platelets may result in bleeding. HIT can (rarely) occur shortly after heparin is given, but also when a person has been on heparin for a long while. Immunologic tests are available for the diagnosis of HIT. There is also a benign form of thrombocytopenia associated with heparin use. In case of overdose, protamine sulphate can be given to counteract the action of heparin. Low molecular weight heparin is a more highly processed product that is useful as it does not require monitoring of the APTT coagulation parameter (it has more predictable plasma levels) and has fewer side effects. See eBNF.
Dose	Heparin has to be adminstered parenterally: it is digested when taken by mouth. It can be injected intravenously, into a muscle, or subcutaneously (under the skin). Because of its short biologic half-life of approximately one hour, heparin must be given frequently or as a continuous infusion. See eBNF.
Interactions	See eBNF.
Contraindications	not specified
Comments	If long-term anticoagulation is required, heparin is commonly only used to commence anticoagulation therapy until the oral anticoagulant warfarin is working effectively. Heparin initiates anticoagulation rapidly but has a short duration of action. It is now often referred to as being standard or unfractionated heparin to distinguish it from the low molecular weight heparins, which have a longer duration of action. For patients at high risk of bleeding, heparin is more suitable than low molecular weight heparin because its effect can be terminated rapidly by stopping the infusion. Bemiparin, dalteparin, enoxaparin, reviparin, and tinzaparin are low molecular weight heparins. Low molecular weight heparins are as effective and as safe as unfractionated heparin in the prevention of venous thrombo-embolism; in orthopaedic practice they are probably more effective. They have a longer duration of action than unfractionated heparin; once-daily subcutaneous dosage means that they are convenient to use. The standard prophylactic regimen does not require monitoring. Some low molecular weight heparins are also used in the treatment of deep-vein thrombosis, pulmonary embolism, unstable coronary artery disease and for the prevention of clotting in extracorporeal circuits. OTHER ANTICOAGULANTS. Warfarin (see separate entry). Danaparoid is a heparinoid used for prophylaxis of deep-vein thrombosis in patients undergoing general or orthopaedic surgery. Providing there is no evidence of cross-reactivity, it also has a role in patients who develop thrombocytopenia in association with heparin. Lepirudin, a recombinant hirudin, is licensed for anticoagulation in patients with Type II (immune) heparin-induced thrombocytopenia who require parenteral antithrombotic treatment. The dose of lepirudin is adjusted according to activated partial thromboplastin time (APTT). Bivalirudin, a hirudin analogue, is a thrombin inhibitor which is licensed as an anticoagulant for patients undergoing percutaneous coronary intervention. Epoprostenol (prostacyclin) can be given to inhibit platelet aggregation during renal dialysis either alone or with heparin. It is also licensed for the treatment of primary pulmonary hypertension resistant to other treatment, usually with oral anticoagulation. Since its half-life is only about 3 minutes it must be given by continuous intravenous infusion. It is a potent vasodilator and therefore its side-effects include flushing, headache, and hypotension. Fondaparinux sodium is a synthetic pentasaccharide that inhibits activated factor X. It is licensed for prophylaxis of venous thromboembolism in those undergoing major orthopaedic surgery of the legs. Tirofiban inhibits glycopreotein (GP) receptors IIa and IIIb on thrombocytes: rapid onset, short duration of action.
Contributors