After reading this article you will learn about the classification of anticoagulants.
The principal uses of anticoagulants are in vitro to prevent clotting of blood for transfusion or diagnostic use and in vivo to prevent development and enlargement of thrombi.
In Vitro Anticoagulants:
Essentially two categories of chemicals are used: those employed as anticoagulants in samples of blood intended for physical or chemical examination and those employed to preserve blood for transfusion. Certain of these agents can be used to prevent clotting both in vitro and in vivo (heparin), while others may be good for use in vitro, but are not practical in vivo because of their toxicity (oxalates).
(A) Anticoagulant agents used in laboratory examination of blood include:
(i) Sodium oxalate (20%) → 0.01 ml/ml of blood.
(2 mg/ml of blood)
(ii) Sodium citrate (25%) → 0.01 ml/ml of blood (2.5 mg/ml blood)
(iii) Edetate disodium (Sod. versenate) → (EDTA) (2%) → 0.01 ml/ml blood (0.2 mg/ml blood)
(iv) Heparin sodium – 75 i.u./10 ml of blood (1 mg = 100 i.u)
Any of these anticoagulants may be added to sample tubes in the desired amounts and evaporated to dryness. Sterile vacuum tubes that contain appropriate anticoagulants and double needles for ease in blood collection are now available.
(B) Anticoagulants used for blood and blood plasma transfusion include:
(C) Other means also may prevent or retard coagulation.
(i) Cold at 2-5°C.
(ii) Collection of blood into a receptable having smooth and unwettable walls, e.g. paraffin, or silicone coated.
Systemic Anticoagulants:
Two types of anticoagulants are used therapeutically for preventing enlargement of thrombi.
(i) Heparin-used parenterally. It has a direct and almost instantaneous action on the coagulation process.
(ii) Coumarin derivatives-used orally. They have an indirect anticoagulant effect by acting as vitamin K antagonists.
Therefore, action by the coumarin derivatives is delayed for several hours. For emergency treatment, heparin is used first then may be followed by the coumarin derivatives.
Other anticoagulants include edentate sodium, sod. oxalate, and sod. citrate, which hinder coagulation by combining c̅ Ca2+. That’s why these are not useful in vivo. Both categories of the systemic anticoagulants act by inhibition of the action of formation of one or more clotting factors.
Heparin:
(i) Heparin sodium is the only anticoagulant drug used parenterally. Heparin is present in mast cells along with histamine and serotonin and prepared commercially from bovine lung and porcine intestinal mucosa.
(ii) Heparin is highly negatively charged mucopolysaccharide, having larger molecular size. That’s why it is administered parenterally.
Mech. of Action and Pharmacological Effects:
(i) Heparin prolongs clotting time to blood both in vivo and in vitro.
(ii) Heparin prevents fibrin formation in the process of coagulation.
(a) It increases the activity of antithrombin III.
(b) Antithrombin III then inhibits the conversion of prothrombin to thrombin by thromboplastin.
(c) Antithrombin III also directly inactivates thrombin (only in presence of heparin).
[Heparin exerts its anticoagulant action by combining with the endogenous α – 2 globulin called antithrombin III or heparin cofactor’. This combination markedly accelerates the antagonistic action of antithrombin III on thrombin. With thrombin inactivated, conversion of fibrinogen to fibrin is restricted. The heparin antithrombin complex is also inhibitory to the activated forms of other clotting factors-factors IX, X, XI, XII and kallikrein.]
(iii) Heparin decreases aldosterone secretion, increases the concentration of free thyroxine.
(iv) It slows wound healing and probably also depresses cell-mediated immunity.
Therapeutic Uses:
(i) In prophylaxis and treatment of venous thrombosis and pulmonary embolism.
Venous (red) thrombi consist of a fibrin network en-mashed with RBCs and platelets. The anticoagulants are generally ineffective in the treatment of arterial (white) thrombi, made up of adhering platelets. Arterial thrombi are treated with the antithrombotics and thrombolytics.
(ii) In atrial fibrillation with embolization.
(iii) In diagnosis and treatment of chronic consumptive coagulopathies.
(iv) As an anticoagulant in blood transfusion.
(v) For prevention of clotting in arterial and heart surgery.
(vi) For prevention of cerebral thrombosis.
Heparin sodium for inj. contains 10mg (or 1000 units) or more/ml. For i.v. admn., dilution is made with normal saline or 5% glucose (10 mg per 1000 ml) and is dripped slowly as needed.
Coumarin Derivatives:
(i) Drugs under this group are Dicumarol (Bishydroxy-coumarin) and warfarin [3-(α-acetonyl- benzyl) -4 hydroxycoumarin]. Coumarin, normally present in some species of sweet clover, has no anticoagulant action.
(ii) Warfarin sodium is the drug of choice and is considered the prototype of the coumarin- derived anticoagulants.
(iii) These are oral anticoagulants.
(iv) These are vitamin K antagonists.
Mechanism of Action and Pharmacological Effects:
(i) The oral anticoagulants are antagonists of vit. K. Coagulation factors II (prothrombin), VII, IX and X and anticoagulant protein is ‘C’ and ‘S’ are biologically inactive unless certain glutamic acid residues (9 to 12 in number) are carboxylated by a microsomal enzyme system that utilizes reduced vitamin K as a cofactor. Oral anticoagulants prevent reduction of vitamin K.
So, coumarin-derived anticoagulants interfere with vit-K- dependent synthesis of ‘active’ coagulation factors II, VII, IX, and X and proteins ‘C’ and ‘S’.
(ii) The oral anticoagulants are effective only in vivo, and take 8-12 hours for action.
Therapeutic Uses:
(i) Widely used in secondary prophylactic treatment of venous thrombosis and Pulmonary embolism to prevent the recurrence or extension of venous thrombus formation.
(ii) Since oral anticoagulants have no effect on platelet, they are not used in the treatment of thrombotic disease in the arterial system.
Drug Interactions with Oral Anticoagulants:
(i) Acetylsalicylic acid, cimetidine, phenylbutazone, oxyphenbutazone, cotrimoxazole, metronidazole, disulfiram, clofibrate, etc. increase the response to anticoagulants.
(ii) Rifampin, cholestyramine, glutethimide and barbiturates reduce the efficacy of anticoagulants.
Coagulants:
Classification:
1. Fresh whole blood or plasma.
2. Vitamin K:
(i) K1 (from plants, fat soluble) → Phytonadione (Phylloquinone)
(ii) K2 (produced by bacteria) → Menaquinones.
(iii) K3 (Synthetic):
(a) Fat soluble → (i) Menadione (ii) Acetomenaphthone
(b) Water soluble → (i) Menadione Sod. bisulfite.
(ii) Menadiol Sod. diphosphate.
3. Miscellaneous:
(i) Fibrinogen (human)
(ii) Antihaemophilic factor
(iii) Tissue extract
(iv) Adrenochrome monosemicarbazone
(v) Rutin.