Heparin is a glycosaminoglycan found in mast cells that acts as an anticoagulant by catalyzing the inhibition of coagulation factors like thrombin and factor Xa by antithrombin. It is commonly extracted from pig intestines or cow lungs. Low molecular weight heparins produced by fractionation have a higher affinity for inhibiting factor Xa over thrombin. Heparin is used to prevent and treat deep vein thrombosis and pulmonary embolism and in other conditions like myocardial infarction and unstable angina. Adverse effects include heparin-induced thrombocytopenia and osteoporosis with prolonged use.

1. HEPARIN
DR.VENKATESH.K
JR
UROLOGY

2. • Heparin is a glycosaminoglycan found in the
secretory granules of mast cells.
• Molecular weight of 10,000-40,000.
• Polymer 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% CaCl2.

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.

10. 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.

11. • 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.

12. 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.

13. 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.

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

15. Contraindication:
• Hypersensitivity.
• Actively bleeding or hemophilia, significant
thrombocytopenia, purpura.
• Severe hypertension.
• Intracranial hemorrhage.
• Infective endocarditis, active tuberculosis,
ulcerative lesions of the gastrointestinal tract.

16. 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.

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

18. 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.

19. 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.

20. Thank u