Heparin

heparin in detail : mechanism of action, pharmacokinetics, clinical uses, adverse effect and contraindication of heparin and low molecular heparin.
for undergraduates.

1. Heparin by: Bibi UMEZA

2. Coagulation pathways

3. 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

4. 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.

5. 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

6. 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 .

7. 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.

8. 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).

9. 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.

10. 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

11. Mechanism of action

12. 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

13. Thank you