Anticoagulants

Anticoagulants are agents that inhibit coagulation of blood either in vitro or in vivo. The in vitro anticoagulants are useful in the collection of blood for laboratory analysis or for blood transfusion.

In vitro anticoagulants

1. Anticoagulants useful for blood collection for laboratory use include
   • Sodium oxalate 20% solution at 0.01ml/ml of blood
   • Sodium citrate 25% solution at 0.01ml/ml of blood
   • Edetate disodium (EDTA) 2% solution at 0.01ml/ml of blood
   • Heparin sodium 75 IU/10 ml of blood
2. Anticoagulants useful for blood collection for transfusion include
   • Sodium citrate solution at 10 ml/90 ml of blood containing Sodium citrate 2.5 g, sodium chloride 0.9 g and distilled water to make 100 ml
   • ACD solution – Acid citrate dextrose solution at 15 ml/100 ml of blood containing Sodium citrate 2.5 g, citric acid 0.8 g, dextrose 2.5 g and distilled water to make 100 ml
   • Heparin sodium at 400 to 600 IU/100 ml of whole blood
3. In addition to the above agents applying cold at 2 to 5 C or collecting blood in a receptacle having smooth or unwettable walls like silicon coated receptacles can also be used to collect blood without coagulation.

In vivo anticoagulants

Heparin is used as Systemic anticoagulants or In vivo type anticoagulant. here are some features of heparin listed below-

1. Heparin is used both as in vitro and in vivo anticoagulant. Heparin is used parenterally as an anticoagulant.
2. Heparin has direct and almost instantaneous action on the coagulation process.
3. Heparin is present in mast cells along with histamine and serotonin and is prepared commercially from bovine lung and porcine intestinal mucosa.
4. Heparin is a highly negatively charged mucopolysaccharide having larger molecular size and hence is administered parenterally.
5. Heparin prolongs the clotting time of blood both in vivo and in vitro.
6. Heparin prevents fibrin formation in the process of coagulation.
7. Heparin increases the activity of antithrombin III.
8. Antithrombin III then inhibits the conversion of prothrombin to thrombin by thromboplastin.
9. Antithrombin III also directly inactivates thrombin in the presence of heparin.
10. Heparin decreases aldosterone secretion, increases the concentration of free thyroxine.
11. Heparin slows wound healing and depresses cell mediated immunity.

Clinical uses of anticoagulants

1. Prophylaxis and treatment of venous thrombosis and pulmonary oedema
2. In atrial fibrillation with embolization
3. In the diagnosis and treatment of chronic consumptive coagulopathies.
4. As an anticoagulant in blood transfusion
5. For the prevention of clotting in atrial and cardiac surgery
6. For prevention of cerebral thrombosis

Oral anticoagulants: Coumarin derivatives

• Coumarin is normally present in some species of sweet clover and has no anticoagulant activity.
• The derivatives of coumarin namely dicumarol (bishydroxy coumarin) and warfarin are coumarin derivatives.
• Warfarin sodium is the drug of choice and is the prototype coumarin derivative anticoagulant.
• Coumarin derivatives are used as oral anticoagulants.
• They are vitamin K antagonists.
• They take about 8 – 12 hours to produce their action.
• They are widely used in secondary prophylactic treatment of venous thrombosis and pulmonary embolism.
• Aspirin, cimetitidine, phenylbutazone, oxyphenbutazone, cotrimoxazole, metronidazole and disulfiram increase the response to anticoagulants.

Heparin antagonist

Protamine sulphate is a strongly basic low molecular weight protein obtained from the sperm of certain fish. It given intravenously it neutralizes the heparin weight for weight. In the absence of heparin, protamine sulphate itself acts as a weak anticoagulant