This document discusses anticoagulants, including heparin. It defines anticoagulants as drugs used to reduce blood coagulability and classifies them into those used in vivo and in vitro. It provides details on heparin, including its discovery, chemistry, mechanisms of action, pharmacokinetics, dosage, adverse effects, contraindications, and uses.

1. ANTICOAGULANTS
Suresh Kumar Ghritlahare
SRU, Raipur, (C.G.)

2. ANTICOAGULANTS
ANTICOAGULANTS:These are drugs used to reduce the
coagulability of blood. They may be classified into:
I. Used in vivo
A. Parenteral anticoagulants:
(i) Indirect thrombin inhibitors: Heparin, Low molecular weight
heparins, Fondaparinux, Danaparoid
(ii) Direct thrombin inhibitors: Lepirudin, Bivalirudin, Argatroban
B. Oral anticoagulants:
(i) Coumarin derivatives: Bishydroxycoumarin (dicumarol), Warfarin
sod, Acenocoumarol (Nicoumalone), Ethylbiscoumacetate
(ii) Indandione derivative: Phenindione.
(iii) Direct factor Xa inhibitors: Rivaroxaban
(iv) Oral direct thrombin inhibitor: Dabigatran etexilate
II. Used in vitro
A. Heparin: 150 U to prevent clotting of 100 ml blood.
B. Calcium complexing agents: Sodium citrate: 1.65 g for 350 ml of
blood; used to keep blood in the fluid state for transfusion

3. HEPARIN
HEPARIN: McLean, a medical student, discovered in
1916 that liver contains a powerful anticoagulant.
Howell and Holt (1918) named it ‘heparin’ because it
was obtained from liver.
Chemistry and occurrence: Heparin is a non-uniform
mixture of straight chain mucopolysaccharides with
MW 10,000 to 20,000. It contains polymers of two
sulfated disaccharide units:
• D-glucosamine-Liduronic acid
• D-glucosamine-Dglucuronic acid
Heparin carries strong electronegative charges and is
the strongest organic acid present in the body

4. ACTIONS
1. Anticoagulant: Heparin is a powerful and
instantaneously acting anticoagulant,
effective both in vivo and in vitro.
It acts indirectly by activating plasma
antithrombin III (AT III, a serine proteinase
inhibitor). The heparin-AT III complex then
binds to clotting factors of the intrinsic and
common pathways (Xa, IIa, IXa, XIa, XIIa and
XIIIa) and inactivates them but not factor VIIa
operative in the extrinsic pathway.

6. 2. Antiplatelet :Heparin in higher doses inhibits
platelet aggregation and prolongs bleeding
time.
3. Lipaemia clearing :Injection of heparin
clears turbid post-prandial lipaemic plasma by
releasing a lipoprotein lipase from the vessel
wall and tissues, which hydrolyses
triglycerides of chylomicra and very low
density lipoproteins to free fatty acids.

7. PHARMACOKINETICS
• Absorption: Heparin is a large, highly ionized
molecule; therefore not absorbed orally. Injected
i.v. it acts instantaneously, but after s.c. injection
anticoagulant effect develops after ~60 min.
• Distribution: Bioavailability of s.c. heparin is
inconsistent. Heparin does not cross blood-brain
barrier or placenta (it is the anticoagulant of
choice during pregnancy).
• Metabolism: It is metabolized in liver by
heparinase
• Excreation: Excreted in urine.

8. Dosage :Heparin is conventionally given i.v. in a bolus
dose of 5,000–10,000 U (children 50–100 U/kg),
followed by continuous infusion of 750–1000 U/hr.
Intermittent i.v. bolus doses of UFH are no longer
recommended.
Adverse effects:
1. Bleeding due to overdose is the most serious
complication of heparin therapy.
2. Thrombocytopenia is another common problem.
3. Transient and reversible alopecia is infrequent. Serum
transaminase levels may rise.
4. Osteoporosis may develop on long-term use of
relatively high doses.
5. Hypersensitivity reactions are rare;

9. Contraindications:
1. Bleeding disorders, history of heparin induced
thrombocytopenia.
2. Severe hypertension (risk of cerebral haemorrhage),
threatened abortion, piles, g.i. ulcers (risk of
aggravated bleeding).
3. Subacute bacterial endocarditis (risk of embolism),
large malignancies (risk of bleeding in the central
necrosed area of the tumour), tuberculosis (risk of
hemoptysis).
4. Ocular and neurosurgery, lumbar puncture.
5. Chronic alcoholics, cirrhosis, renal failure.
6. Aspirin and other antiplatelet drugs should be used
very cautiously during heparin therapy.

10. USES OF ANTICOAGULANTS
1. Deep vein thrombosis (DVT) and pulmonary
embolism (PE)
2. Myocardial infarction (MI)
3. Unstable angina
4. Rheumatic heart disease; Atrial fibrillation
(AF)
5. Cerebrovascular disease

11. References
• Tripathi KD, “Essentials of Medical
Pharmacology” published by Jaypee Brothers
Medical Publishers (P) Ltd, Seventh Edition:
2013, New Delhi, p.p. no-616-620.