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Heparin

Heparin is a glycosaminoglycan used as an anticoagulant, primarily to treat venous thrombosis and pulmonary embolism, among other conditions. It works by catalyzing reactions involving antithrombin and thrombin, with a rapid intravenous onset and variable subcutaneous bioavailability. Low molecular weight heparins, derived from heparin, have improved properties like better bioavailability and no requirement for APTT monitoring.

Health & Medicine◦
Heparin by: Bibi UMEZA
Coagulation pathways
Heparin • Heparin is a Glycosaminoglycan • Secretory granules of mast cells • Commercial heparin – Porcine intestinal mucosa, Bovine lung • Doses are specified in units of activity – 150units/mg
Mechanism of action of Heparin • Heparin acts as a catalytic template for both antithrombin and thrombin. • Increases the rate of reaction by 1000 fold. • Conformational change in antithrombin – facilitates reaction with Xa. (LMW heparins) • Interfere with platelet aggregation • Releases lipoprotein lipase.
Pharmacokinetics • No oral route • Intravenous – Immediate onset of action • Subcutaneous route – delayed by 1-2hrs • Half life 1-5 hrs • Anticoagulant of choice in pregnancy
Clinical uses • Venous thrombosis and pulmonary embolism. • Unstable angina or acute myocardial infarction. • During and after coronary angioplasty or stent placement. • Low dose s/c heparin in Preventing venous thromboembolism.
Administration and monitoring • Intravenous bolus of 5000units followed by 750- 1000units/hr infusion. OR • Deep s/c injection of 10,000-20,000 units every 8-12hrs. • Low dose s/c regimen: 5000units every 8-12hrs. • Activated partial thromboplastin time (aPTT) is maintained at 1.5-2.5 times the patients pretreatment value.
Adverse effects • Bleeding (Protamine sulfate 1mg neutralizes 100u heparin) • Thrombocytopenia Other less frequent toxicities • Mild elevations of serum transaminase levels • Osteoporosis • Hyperkalemia • Allergic reactions (rare).
Contraindications • Bleeding disorders, • Heparin induced thrombocytopenia • Severe hypertension, threatened abortion, piles, peptic ulcers • Subacute bacterial endocarditis, large malignancies, tuberculosis. • Ocular and neurosurgery and lumbar puncture • Caution when patient is on aspirin or other anticoagulants.
LMW Heparins • Heparin is fractionated into LMW forms • Selectively inhibit factor Xa • Act only by inducing conformational change in AT III • Hence smaller effect on aPTT • Eg. Enoxaparin, Reviparin, Nadroparin, Dalteparin, Fondaparinux
Mechanism of action
Heparin Vs LMW heparin Heparin • High molecular weight (10,000-20,000) • SC bioavailability variable • Short duration of action • aPTT ( activated partial thromboplastin time) monitoring • Interacts with platelets • Antigenic, Can cause Thrombocytopenia • Cheap LMW heparin • Low molecular weight (3000- 7000) • Better SC bioavailability • Longer duration of action (OD, SC) • aPTT monitoring not required • Interacts less with platelets • No thrombocytopenia • Slightly expensive
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