Heparin

heparin anti coagulant

1. HEPARIN DR.VENKATESH.K JR UROLOGY

2. Heparin is a glycosaminoglycan found in the secretory granules of mast cells. M olecular weight of 10,000-40,000. P olymer of alternating D- glucuronic acid and N -acetyl-D-glucosamine residues. Heparan sulfate on the surface of vascular endothelial cells or in the subendothelial extracellular matrix interacts with circulating antithrombin ( see below) to provide a natural antithrombotic mechanism.

3. imp Patients with malignancies may experience bleeding related to circulating heparan sulfate or related glycosaminoglycans that probably originate from lysis of the tumor cells.

4. Source: Heparin is commonly extracted from porcine intestinal mucosa or bovine lung. Biological activity is measured in USP units. The USP unit is the quantity of heparin that prevents 1 ml of citrated sheep plasma from clotting for 1 hour after the addition of 0.2 ml of 1% CaCl 2 .

5. LMW-HEPARIN Low-molecular-weight heparins (1000 to 10,000 daltons ; mean, 4500 daltons , or 15MS units) are isolated from standard heparin by gel filtration chromatography, precipitation with ethanol, or partial depolymerization with nitrous acid and other chemical or enzymatic reagents. Activity measured by factor- Xa inhibition assay, mediated by antithrombin .

6. MOA Heparin catalyzes the inhibition of several coagulation proteases by antithrombin . AT- inhibits activated coagulation factors of the intrinsic and common pathways, including thrombin, Xa , and IXa . Heparin increases the rate of the thrombin- antithrombin reaction at least a thousandfold by serving as a catalytic template to which both the inhibitor and the protease bind.

7. The binding site for antithrombin on heparin is a specific pentasaccharide sequence that contains a 3-O-sulfated glucosamine residue. This structure occurs in about 30% of heparin molecules and less abundantly in heparan sulfate. Heparin molecules containing fewer than 18 monosaccharide units (<5400 daltons ) also do not catalyze inhibition of thrombin by antithrombin .

8. High-molecular-weight ( HMW ) fractions of heparin with high affinity for antithrombin markedly inhibit blood coagulation by inhibiting all three factors, especially thrombin and factor Xa Low-molecular-weight heparin preparations produce an anticoagulant effect mainly through inhibition of Xa by antithrombin , because the majority of molecules are of insufficient length to catalyze inhibition of thrombin.

9. When the concentration of heparin in plasma is 0.1 to 1 units/ml, thrombin, factor IXa , and factor Xa are inhibited rapidly (half-lives less than 0.1 second) by antithrombin .

10. Bound forms of clotting factors are not inhibited by heparin. Platelet factor 4, released from the a-granules during platelet aggregation, blocks binding of antithrombin to heparin or heparan sulfate and may promote local clot formation at the site of hemostasis .

11. High dose It can interfere with platelet aggregation and there by prolong bleeding time. At lower doses Heparin "clears" lipemic plasma in vivo by causing the release of lipoprotein lipase into the circulation. Lipoprotein lipase hydrolyzes triglycerides to glycerol and free fatty acids.

12. USES: Prevention and treatment of DVT and pulmonary embolism intermittent low dose heparin admin-5000IU sc 8-12hrly. LMW heparin- enoxaparin 30mg sc 12hrly -dalteparin5000U,s.c/day Infusion in case of estd thrombus.

13. Contd … Myocardial infarction: prophylaxis,during coronary angioplasty and stent placement. Unstable angina: reduce chances of MI. Miscellaneous: DIC,peripheral embolism,during hemodialysis .

14. Contraindication: Hypersensitivity. A ctively bleeding or hemophilia , significant thrombocytopenia, purpura . S evere hypertension . I ntracranial hemorrhage. Infective endocarditis , active tuberculosis, ulcerative lesions of the gastrointestinal tract.

15. Contd.. Threatened abortion, visceral carcinoma, or advanced hepatic or renal disease. Avoided in those patients who have recently had surgery of the brain, spinal cord, or eye. Patients who are undergoing lumbar puncture or regional anesthetic block.

16. S.E of Heparin: HIT Osteoporosis and spontaneous fractures on prolonged use. Transient alopecia. Hypersensitivity.

17. LMWH: advantages Given by s.c -better bioavailability 70-90% Longer elemination half-life- once daily dosing Do not prolong APTT and whole blood clotting time- monitorng is not requiredas with UFH. Dose is given in mg not in units.

18. FONDAPARINUX Synthetic derivative. Dose-2.5mg OD 6hrs after Sx . S.C route 100% bioavailability. Half-life-17-21hrs Excreted unchanged in urine-CI when cr. Clearance is<30ml/min.

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