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  1. Warfarin
    1. MC used oral anticoagulant
    2. Inhibits II, VII, IX, X biosynthesis (blocking gamma carboxylation in liver)
    3. Dicumurol derivative (coumarins)
      1. Developed by WARF (Wisconsin Almuni Research Foundation)
      2. Rat poison


  1. Well absorbed (100%)
  2. Latency of 1-3 days, before action starts
  3. 99% protein bound
  4. Half life is 8 hours
  5. Zero order kinetics


  1. Deep vein thrombosis                  
  2. Pulmonary embolism                   
  3. Pulmonary hypertension                        
  4. Recurrent thromboembolism            
  5. Restenosis following angioplasty                  
  6. Thrombotic stroke
  7. Atrial fibrillation                          
  8. Following angioplasty                   
  9. Following valvoplasty



  1. Prothrombin time/INR (International Normalized Ratio)
    INR = patient prothrombin time/(mean of normal prothrombin time for lab)ISI
    *ISI exponent refers to the International Sensitivity Index, and is dependent on the specific reagents and instruments used for the determination
  2. INR = 1 (normal patient)
  3. INR= 2-3 times normal value (prophylaxis and treatment of thrombotic disease)
  4. INR= 2.5-3.5 times normal value (artificial heart valve, risk of thrombotic events)

Side effects

  1. MC-bleeding (into the gut)
  2. Alopecia
  3. Osteomalacia Necrosis
    i. Bone                     
    ii. Fat                       
    iii. Pancreas     
    iv. Gut                     
    v. Skin                     
    vi. Breast

Extra edge: Necrotic lesions are more common in protein C & also in protein S deficiency

  1. Highly teratogenic, c/I in pregnancy.

Drug interactions

  1. Absorption reduced by cholestyramine, liquid paraffin- clotting
  2. Displacement by chloral hydrate- Bleeding
  3. Griseofulvin-metabolism is induced-clot
  4. Cimetidine, omeprazole, fluoxetine inhibit metabolism-bleeding
  5. Haparin+warfarin-bleeding
  6. Warfarin+aspirin- Bleeding
  7. Warfarin+quinidine- bleeding
  1. Heparins
    1. Heparins are mucopolysaccharides
    2. Derivatives of chondroitin sulphate
    3. Strongest acid in body
    4. Mast cells-richest source
    5. Commercial-bovine mucosa/hog lungs /porcine intestine

Two types

  1. High molecular weight heparins (HMWH)
    1. Less commonly used now
  2. Low molecular weight heparins (LMWH)
    1. Dalteparin
    2. Tinzaparin
    3. Enoxaparin


  1. Longer acting
  2. Safer  


  1. Increases factor = antithrombin III activity
  2. Inhibit factor-II, VII, IX, X, XII (mainly Xa)


  1. Not absorbed orally Rivoroxaban however is a heparinoid compound; popularly known as “oral heparin”
  2. Half life=1 hour
  3. Metabolism occurs in liver; half life increases in liver & kidneys disease
  4. Zero order kinetics
  5. 99% protein bound
  6. No latency of onset of action
  7. Never given IM (hematoma occurs)  


  1. Same as warfarin
  2. Can be used in Pregnancy


  1. aPTT measurement
  2. Xa titration and Protamine assay (in pregnancy, obese and renal disease)
  3. LMWH do not require monitoring

Side effects

  1. MC-bleeding (HIB)                        
  2. Clotting (HIC)              
  3. Thrombocytopenia (HIT)                      
  4. Osteoporosis                        
  5. Hyperkalemia                              
  6. Alopecia


  1. Head injury                          
  2. Recent surgery    
  3. Active tuberculosis              
  4. Neurosurgery
  5. Ocular surgery                            
  6. Active bleeding     
  7. Visceral cancer                            
  8. Threatened abortion
  9. Infective endocarditis                  
  10. Peptic ulcer

When to stop heparin

  1. Heparin induced bleeding (HIB)
  2. Heparin induced thrombocytopenia (HIT)
  3. Heparin induced clotting (HIC) 

Heparin induced Bleeding

Hematuria is earliest manifestation

Rx-protamine sulphate (antidote)

Sparingly used

Bleeding can occur

1 mg is used for 100 units

Heparin induced Thrombocytopenia

Heparin damages platelets

Lepirudin is DOC

Eliminated by kidney.

In CRF patients, Argatroban is DOC.


Heparin Induced Clotting

a. Platelet fibrin clot       

b. Mainly in venous location (80%)

c. Can also be arterial in location                

d. White in color (contains no RBC)

e. Rx-Streptokinase

  1. DTI: (Direct Thrombin Inhibitors)

Can be given by two routes:




Dabigatran etixilate mesylate

Hirudin, Bivalirudin, Lepirudin, Argatroban

1st oral Direct Thrombin Inhibitor

Approved in 2011

Prophylaxis of stroke and embolism in AF patient

Can replace warfarin for this indication

S/E bleeding,

Monitoring is req. in CRF pts


1st DTI

Obtained from leech saliva

S/E: HSN reaction, No longer used.



DOC: Heparin Induced Thrombocytopenia (HIT)

Eliminated by Kidney

C/I in CRF pts



Shortest acting DTI

Useful for PCA



DOC:  HIT syndrome in CRF pts

Eliminated by liver

  1. Oral factor Xa inhibitors
    1. Apixaban
    2. Rivaroxaban: Approved for prevention of venous thromboembolism following hip or knee surgery.
      1. Very potent drug
      2. Monitoring is not required
      3. C/I in CRF patient


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