This document discusses anticoagulants, including their classifications, mechanisms of action, and uses. It focuses on heparin and warfarin. Heparin is an indirect thrombin inhibitor that acts invitro and invivo, while warfarin is an oral anticoagulant that inhibits vitamin K-dependent clotting factors in the liver and has a slower onset of action than heparin. Both drugs are used to prevent pathological thrombosis and clots but have different pharmacokinetic properties and monitoring requirements.

1. ANTI-
COAGULANTS

2. Coagulants contd……
TERMINOLOGIES:
Thrombosis:
Formation of an unwanted clot within a
blood vessel (most common abnormality )
Thrombus:
A clot that adhere to a vessel wall
Embolus:
An intravascular floating clot

3. Coagulants contd……
Types of thrombus:
1. White thrombus (arteries)
2. Red thrombus (veins)
Pathological Thrombus
⇒ Myocardial Infarction (MI)
⇒ Deep-vein Thrombosis
⇒ Acute Ischemic Stroke
⇒ Pulmonary Embolism etc

4. ANTICOAGULANTS:
 Prevent pathologic thrombosis
 Used for prophylaxis (Not Treatment)
 Effective in red thrombus

5. CLASSIFICATION:
1. Used invitro:
Heparin, Calcium complexing agents (Sod. Citrate,
Sod. Oxalate, Sod. Edetate)
2. Used invivo:
A) Parenteral anticoagulants:
i) Indirect thrombin inhibitor: Heparin,
Low molecular weight heparin (LMWH)
ii) Direct thrombin inhibitor: Lepirudin, Danaparoid,
Hirudine
B) Oral anticoagulants:
i) Coumarin derivatives: Warfarin sod., Dicumarol,
Acenocoumarol
ii) Indandione derivatives: Phenindione
Anti-coagulants contd……

6. HEPARIN (unfractionated heparin):
 Mucopolysaccharides (MW 10,000 –
20,000)
 Organic acid with strong electronegative
charge
 Found in all tissue containing mast cells;
richest in Lung, Liver, Intestinal mucosa
etc
Mechanism of action:
 Effective in both invivo & invitro
 It inactivates the activated clotting factors
Anti-coagulants contd……

7. Anti-coagulants contd……
Intrinsic pathway Extrinsic pathway
XII XIIa* VIIa VII
XI XIa*
Ca++
IX IXa* Ca++ III
Ca++ Pl. Ph Phospholipid
X Xa* X
V Pl. Ph
Ca++
Prothrombin (II) Thrombin (IIa*)
Fibrinogen Fibrin
* Factors affected by Heparin, Coloured factors affected by Warfarin

8. Pharmacokinetics:
 Not absorbed orally
 Does not cross BBB or placenta
( preferred pregnancy)
 IV (preferred) or SC not IM (Haematoma)
 Dose: IV bolus dose 5,000–10,000 U every
4-6 hrs & maintenance dose 750-1000
U/hr
 Dose monitored by aPTT measurement
Anti-coagulants contd……

9. Adverse effects:
Bleeding ,Osteoporosis (long term use),
Thrombocytopenia, Hypersensitivity reaction
Contraindications:
Bleeding disorder, Thrombocytopenia, Severe
hypertension, Threatened abortion, GI ulcer,
Tuberculosis, Liver cirrhosis, Renal failure
Should be used cautiously in patient on aspirin or
other anti platelet therapy
Protamine Sulfate is antidote for overdose
Anti-coagulants contd……

10. Low Molecular Weight (LMW) Heparin:
e.g. Enoxaparin, Dalteparin, Reviparin, Nadoparin
 Fractionated form of heparin (MW 3000- 7000)
 Selectively inhibit factor Xa & little
effect on IIa
Advantages:
i) Equally efficacious
ii) Better s.c. bioavailability (70-90%)
iii) Longer t1/2 given once a day s.c.
iv) Lab monitoring for dose adjustment is not
needed as aPTT/clotting times are not
prolonged
v) No or less antigenic
Anti-coagulants contd……

11. WARFARIN:
 Inhibit Vit K dependent clotting factors
synthesis in liver
 Act in-vivo only
 Anticoagulant effects appears gradually
over the next 1-3 days
Pharmacokinetics:
 Almost complete oral absorption
 Plasma protein bound: 99% (High)
 Duration of action (3-6 days)
 Crosses placenta & secreted in milk
 Half life = 36-48 hrs
Anti-coagulants contd……

12. Adverse effects:
Bleeding, Skin necrosis (purple toe
syndrome), Alopecia, teratogenicity
Dose regulation:
Measuring Prothrombin Time (PT) or INR
Drug Interactions:
A large number of drug interact with oral
anticoagulant see KDT
Anti-coagulants contd……

13. Uses of anti-coagulants:
 Primary & secondary prevention of thrombus
and emboli complications
 Effective in Red thrombus
 Generally Heparin and warfarin are started
together; heparin is discontinued after few
days but warfarin continued
1. Deep-vein thrombosis & pulmonary embolism
2. Myocardial Infarction (MI) & Unstable angina; less
effective
3. Rheumatic heart disease, Atrial fibrillation
4. Cerebrovascular disease
5. Vascular surgery, retinal vessel thrombosis,
orthopedic surgery, Haemodialysis
Anti-coagulants contd……

14. Anti-coagulants contd……
Feature Heparin Warfarin
Chemical
Nature
Large
Polysaccharide
Small molecule
Water soluble Lipid soluble
Kinetics
Given parenterally
(i.v., s.c.), Not i.m.
Given orally
t1/2= 2h
98% protein bound,
liver metabolism, t1/2
>30
no placental
access
Placental access
Comparative properties of Heparin & Warfarin

15. Anti-coagulants contd……
Feature Heparin Warfarin
Mechanism
Inactivate the
activated clotting
factors
↓ hepatic synthesis
of vit. K dependent
factors
Fast acting NO action on already
formed factors, Slow
action
Invivo/ invitro action Only in-vivo action
Monitoring aPTT PT, INR
Antidote
Protamine sulfate Vitamin K
Fast onset Slow onset, Fresh
frozen plasma (fast)
Comparative properties of Heparin &Warfarin Contd……….

16. Anti-coagulants contd……
Feature Heparin Warfarin
Uses
Rapid
anticoagulation
(intensive)
Longer term
anticoagulation
(controlled) in
ambulatory patient
Toxicity
Bleeding,
osteoporosis,
Heparin induced
thrombocytopenia
(HIT),
Hypersensitivity
Bleeding,
Skin necrosis (if low
protein C),
drug interactions,
teratogenicity
Comparative properties of Heparin &Warfarin Contd……….