This document summarizes different types of anticoagulants, including their mechanisms of action, monitoring, and therapeutic uses. It discusses oral anticoagulants like warfarin that act by inhibiting vitamin K, as well as injectable anticoagulants like heparin and novel anticoagulants that directly inhibit coagulation factors. Warfarin is monitored using INR while heparin is monitored using aPTT or anti-Xa assay. Anticoagulants are used to treat conditions involving increased risk of blood clots like deep vein thrombosis, pulmonary embolism, atrial fibrillation, and ischemic stroke.
4. Coagulants
• Agents that promote coagulation of blood
Local agents Systemic agents
astringents Antihemophilic factor
Adrenaline Desmopressin
fibrin Fibrinogen
Gelatin Vitamin k
Oxidized cellulose ethamsylate
5. Anticoagulants
• Drugs that prevent or reduce coagulability of blood.
• Increase the time for blood to clot.
• Used in- deep vein thrombosis
myocardial infraction
unstable angina
atrial fibrillation
thromboembolism
7. Warfarin
Mechanism of action:
Inhibit the activation of vitamin k dependent clotting factors by inhibiting vitamin k epoxide
reductase (VKOR).
gama-Carboxylase
II, VII, IX, X IIa, VIIa, IXa, Xa
VKOR warfarin
Side effects:
• Bleeding – (treatment of choice: fresh frozen plasma, specific antidote: Vit K1)
• Dermal vascular necrosis
• Teratogenic
Vit k epoxide
vit k
hydroquinone
x
8. Heparin
• Produced from ox lung and pig intestine.
• Two types: (1)unfractionated heparin
• (2)low molecular weight heparin
• Act by activating Antithrombin III in plasma.
• AT III inactivates clotting factors Xa and IIa.
Heparin accelerate this process by inducing
conformational changes to AT III
• UFH- inhibit Xa and IIa both
• LMWH- inhibit only Xa
• Anticoagulant of choice during pregnancy.
9. Advantage of LMWH over heparin
Advantage Consequence
• Better bioavailability & longer t1/2 Can be given SC once or twice daily
• Dose independent clearance Simplified clearance
• Predictable response Non need of monitoring
• Lower risk of HIT-syndrome Safer for long term use
• Lower risk of osteoporosis Safer for long term use
Side effects of heparin:
1. Bleeding (treated by fresh frozen plasma. Antidote- protamine)
2. Thrombocytopenia
3. Alopecia
4. Osteoporosis
10. Direct thrombin inhibitors
• Hirudin, lepirudin, dabigatran.
• Directly inactivate factor IIa (thrombin).
• Anticoagulant of choice for heparin induced thrombocytopenia (HIT).
• Excreted by kidney- avoided in renal failure.
Direct factor Xa inhibitor
• Rivaroxaban, edoxaban, apixaban
• Preferred over warfarin in atrial fibrillation
14. Monitoring of anticoagulants
Each type of anticoagulant has different methods for measuring its concentration in the blood
1. Warfarin:
Monitored using- International Normalized Ratio (INR). The INR is a standardized measurement of
how long it takes for the blood to clot compared to a control sample. The test is performed using a
blood sample, and the results are typically reported as a ratio (e.g., 2.0, 2.5). The target INR range
depends on the condition being treated.
2. Heparin:
Measured using- activated partial thromboplastin time (aPTT) or anti-Xa assay. The aPTT measures
the time it takes for the blood to clot after the addition of specific reagents. The anti-Xa assay
measures the activity of heparin by quantifying its ability to inhibit factor Xa, a clotting factor.
3. Direct Oral Anticoagulants (DOACs):
do not require monitoring.
15. Drug interactions
• Warfarin X cholestyramine: reduced absorption of warfarin from gut
• Oral anticoagulants X barbiturates/rifampicin: increase metabolic clearance of
anticoagulants – decrease effect
• Warfarin X salicylates/sulphonamide: these drugs displace warfarin from plasma
protein binding site – increase free plasma conc. of warfarin – bleeding
• Warfarin X alcohol, chloramphenicol, isoniazid: decrease metabolic clearance of
warfarin – increase effect
16. Uses of anticoagulants
In cases where the stroke is caused
by a blood clot (ischemic stroke).
Preventing
clot formation
Dissolving
existing clot
Restoring
blood flow
1.
18. Uses of anticoagulants
when a blood clot, typically originating in
the legs (deep vein thrombosis or DVT),
travels through the bloodstream and
lodges in the pulmonary arteries,
blocking blood flow to the lungs.
Same Anticoagulants are used as DVT.
3.
19. References
• Xia, Y., et al. (2023). "Factor XIa Inhibitors as a Novel Anticoagulation Target: Recent Clinical
Research Advances." Pharmaceuticals 16(6): 866.
• Essentials of medical pharmacology by KD Tripathi.
• Goodman & Gilman’s manual of Pharmacology and therapeutics.
• Review book of pharmacology by Govind Rai Garg and Sparsh Gupta.
• Google.com
• chatGPT
