Platelets and thrombin systems work together to form blood clots. Platelets become activated when bleeding occurs and begin sticking together. Activated clotting proteins engage in chemical reactions producing fibrin strands that stick to vessel walls, trapping red blood cells and forming clots. Anticoagulants prevent clotting by inhibiting factors in the coagulation cascade like thrombin and factor Xa. Heparin is a commonly used anticoagulant that activates antithrombin to inhibit coagulation factors. Newer direct thrombin and factor Xa inhibitors offer more consistent anticoagulation than warfarin with less drug interactions and monitoring requirements.

1. Prepared & Presented By-
KULDIP DEKA : Roll No: 19 : B. Pharm 4th year

2.  Consists of platelets meshed
into fibrin
 A web-like accumulation of
strands with RBCs
 There are two major facets of
the clotting mechanism – the
platelets, and the thrombin
system

3.  Tiny cellular elements, made in the
bone marrow, that travel in the
bloodstream waiting for a bleeding
problem to develop
 When bleeding occurs, chemical
reactions change the surface of the
platelet to make it activated and
become “sticky”
 These activated platelets begin

4.  Calcium ions must be present for the thrombin system
to begin
 The thrombin system consists of several blood proteins
that activate when bleeding occurs
 The activated clotting proteins engage in a chemical
reactions that finally produce a substance called fibrin
 Fibrin strands stick to the exposed vessel wall, clumping
together and forming a web-like complex of strands
 Red blood cells become caught up in the web, causing a
clot

5.  Drugs that help prevent the clotting
(coagulation) of blood
 Coagulation will occur instantaneously once a
blood vessel has been severed
 Blood begins to solidify to prevent
excessive blood loss and to prevent
invasive substances from entering
the bloodstream

6. Classification of
Anticoagulant-
i) Used in vivo-
A) Parenteral anticoagulants-
i) Indirect thrombin inhibitors: Heparin,
Low molecular weight heparins, Fondaparinux,
Danaparoid
ii) Direct thrombin inhibators: Lepirudin,
Bivalirudin,Argatroban

7. B) Oral anticoagulants-
i) Coumarin derivatives: Bishydroxycoumarin,
Warfarin sod,Acenocoumarol
ii) Indandione derivatives: Phenindione
iii) Direct factor Xa inhibators: Rivaroxaban
iv) Oral direct thrombin inhibator: Dabigatran
etexilate
II) Used In vitro
A) Heparine
B) Calcium complexing agents:
E.g. – Sodium citrate

8.  Heparin is a naturally-occurring anticoagulant
produced by basophils and mast cells to prevent
formation and extension of blood clots
 Chemicaly Heparin is a non-uniform mixture contains
polymer of 2 sulfated units having m.w 10,000 to 20,000
 Heparin permits the body's natural clot lysis mechanisms,
i.e. fibrinolysis, to work normally to break down previously
formed clots
 As the thrombokinase is released, it neutralizes the
action of heparin to allow clotting to occur

9. Pharmacological action:
 Heparin is a powerful and instantaneously acting anticoagulant,
effective both in vivo and in vitro.
 It activate indirectly the plasma anti thrombin III and form Heparin-
AT III complex and binds to clotting factors.
 Anticoagulant action is exerted mainly by inhibition of factor Xa as
well as thrombin mediated conversion of fibrinogen to fibrin.
 High dose of heparin inhibits platelets aggregation and prolonged
bleeding time.

10. Pharmacokinetics:
 Heparin is a large, highly ionized molecule therefore not
for orally absorbed.
 Injected i.v. it acts instantneously but in s.c. injection
efeect develops after approx. 60 min.
 Doesn't cross BBB or placenta.
 Metabolites in liver and excreted in urine.
Adverse effects:
-Bleeding due to overdose
-Thrombocytopenia is another common problem
- Osteoporosis may develop on long term use of high
dose.
- In rare Hypersensitivity reactions are occurs.

11. Low molecular weight
heparins(LMWH)
 Low molecular weight heparins (LMWHs) are obtained from
heparin via chemical or enzymatical degradation.This procedure
results in some heparin chains cleaving at the site where thrombin
binds.
 Thus, LMWHs have a reduced capacity to inhibit thrombin, but the
anti-factor Xa activity remains intact as this factor does not need the
thrombin binding site.
Pharmacokinetics-
-Better s.c. bioavailibility 70-90%
- Longer and more consistent monoexponential t ½ : 4-6 hrs.
- Risk of osteoporosis after long time use is less than Heparin.

12. In vivo Parenteral anticoagulants- Directly
thrombin inhibitors:
They are recently developed anticoagulants bind
directly to thrombin and inactivate it without combine with
and activate AT III.
Lepirudin:This recombinant preparation of hirudin binds to
the catalytic and substrate recognition site of thrombin and
inhibit directly.
Injected i.v. in patients who are at risk of heparin
induced thrombocytopenia.
In prolong uses anaphylaxis may occurs.
Its action cant be reversed by any antidote.
Bivalirudin: Smaller peptide prepared synthetically which

13. B)Oral anticoagulants:
Warfarin sodium is an oral medication
It is a synthetic derivative of coumarin,
found naturally in many plants -- it decreases
blood coagulation by interfering with vitamin K
metabolism
It stops the blood from clotting within the
blood vessels and is used to stop existing clots
from getting bigger and to stop parts of clots
breaking off and forming emboli
The most common side effects of warfarin
are bleeding and bruising .
Treatment is monitored by regular blood
testing using the International Normalized Ratio

14. Oral direct thrombin inhibitor:
Dabigatran etexilate:
It is a prodrug which after oral
administration is rapidly hydrolyzed to dabigatran a direct
thrombin inhibitor which reversely blocks the catalytic site of
thrombin and produces a rapid anticoagulant action.
An 'ideal anticoagulant' approved by US FDA.
Dabigatran and apixaban are approved to reduce the
risk of stroke and thrombosis in patients.
• Oral bioavialability is low and effect is consistent.
• Plasma t ½ is 12-14 hrs. and duration of action is 24 hrs.

15. Clinical Use Of Anticoagulants:
1) Deep vein thrombosis(DVT) and pulmonary
embolism(PE)
2) Unstable angina
3) Myocardial infarction(MI)
4) Cerbrovascular disease
5) Rheumatic heart disease
6)Vascular surgery, prosthetic heart valves, retinal vessel
thrombosis, extracorporeal circulation, haemodialysis.
7) Defibrination syndrome.

16. Contraindications:
In case of-
a. Bleeding disorders, history of heparin
induced thrombocytopenia.
b. Severe hypertension, piles, g.i. ulcers
c. Subacute bacterial endocarditis,
tuberculosis.
d. Ocular and neurosurgery, lumbar
puncture.
e. Chronic alcoholics, cirrhosis, renal failure

17. Major Side effects :
A possible side effect of anticoagulants is excessive
bleeding (haemorrhage), because these medicines increase the time
it takes for blood clots to form.
*Signs of excessive bleeding can include:
Passing blood in urine
Severe bruising
Prolonged nosebleeds (lasting longer than 10 minutes)
Bleeding gums
Vomiting blood or coughing up blood
Sudden severe back pain
Difficulty breathing or chest pain
In women, heavy or increased bleeding from vagina
Possible other side effects include:
Diarrhoea or constipation,feeling and being sick,Indigestion,Dizziness ,
headaches,Rashes,itchy skin,hair loss,jaundice etc.

18. References
Book :
Essentials of MEDICAL PHARMACOLOGY
By- KDTripathy:7th edition:Pubilshed by Jaypee
Brothers Medical Publishers(p) Ltd: Section No 10:
Internet :
http://science.j rank.org/pages/419/Anticoagulants-How-
works.html
http://asheducationbook.hematologylibrary.org/cgi/reprint/2
006/1/450
http://www.medic8.com/healthguide/articles/warfarin.html