Anticoagulant

Coni pound no. R Ri R Mustard irritation Granuloma formation  

Lauenstein, Friedrich and Haberland investigated the effects of the parenteral administration of heparin, sodium polyethylene sulphonate and a number of other sulphated polysaccharides on oedema of the rat-foot produced by Zymosan . Two heparin preparations were almost inactive but a heparinoid derived from fungal mycelium exhibited marked effects unaltered by adrenalectomy. These authors conclude that it is unlikely that the anti-inflammatory effects of heparinoids are dependent on anticoagulant activity. 

1-Benzyl-3-[3-(dimethylamino)propoxy]-l//-indazole (AF 864, benzindamine, benzydamine, LI) inhibits various types of foot oedema, formalin peritonitis and granulation tissue in the rat . 

It has been tested clinically as the hydrochloride and possesses antiinflammatory activity in a variety of conditions . 

McKinney and Lish found that aminophylline is active in oral doses of 200 or 400 mg/kg in oedema of the rat-foot produced by carrageenan, dextran and formalin, but only slightly in that induced by 5-hydroxytryp-tamine. On the basis of the carrageenan results, it has a potency about half that of acetylsalicylic acid. It is about one-third as active as acetysalicylic acid in delaying ultra-violet erythema in the guinea-pig, but a toxic effect in this species cannot be excluded in making this assessment. The authors speculate on the extent to which the smooth muscle relaxant or vasodilator properties of aminophylline contribute to these results, and also whether the anti-inflammatory properties contribute to the therapeutic value of the drug in bronchoconstriction. 

A theory of blood clotting introduced in 1905 was based on the existence of four factors thrombopla.stin (thromboki-no.se). prothrombin, librinogcn. and ioni/ed calcium. The clotting sequence proposed was that when tissue damage occurred, thromhoplastin entered the bhxxl from the platelets 

TABLE 19-7 Roman Numerical Nomenclature of Blood-Clotting Factors and Some Common Synonyms  

VIII Antiltcmttphilic factor, antihemophilic globulin, platelet cofactor 1. antihenmpbillc factor A 

IX Pla. nia ihmmboplastin component PTC . Christmas factor, platelet cofnetor II. uutoprothioinbin II. untihcinophilic factor B 

X Stuon Power factor. Stuart factor, autopmthrombin til 

The complex interaction of the factors described above, and a number of endogenous anticoagulant proteins such as protein C, protein S, and antithrombin III normally control the balance between clot formation and clot breakdown.36,61 Disease or inactivity, however, can alter this balance, leading to exaggerated clotting and venous or arterial thrombosis. Drugs used to treat overactive clotting are addressed in the next section. 

Heparin is a large, sugarlike molecule that is poorly absorbed from the gastrointestinal tract. Consequently, heparin must be administered parenterally. The agent was traditionally administered through intravenous (IV) infusion or repeated IV injection 

Inhibit synthesis and function of clotting factors used primarily to prevent and treat venous thromboembolism 

Antithrombotics Inhibit platelet aggregation and platelet-induced clotting used primarily 

Thrombolytics Facilitate clot dissolution used to reopen occluded vessels in arterial 

Although blood clot formation is essential to maintaining haemostasis, inappropriate clotting can give rise to serious, sometimes fatal medical conditions. The formation of a blood clot (a thrombus) often occurs inappropriately within diseased blood vessels. This partially or completely obstructs the flow of blood (and hence oxygen) to the tissues normally served by that blood vessel. 

Anticoagulants are substances that can prevent blood from clotting and, hence, are of therapeutic use in cases where a high risk of coagulation is diagnosed. They are often administered to patients with coronary heart disease and to patients who have experienced a heart attack or 

Heparin Glycosaminoglycan Beef lung, pig gastric mucosa 3 000-40 000 

Hirudin Polypeptide Leech saliva, genetic engineering 7 000 

Ancrod Polypeptide Snake venom, genetic engineering 35 000 

Blood Clotting Enzyme Factor Xa, FXa, or Factor VIIa, FVIIa Inhibitors 

Title Oxybenzamide Derivatives Useful for Inhibiting Factor Xa or Vila 

Nazare el al., US Patent 6,953,857 (October 11, 2005) Assignee Aventis Pharma Deutschland GmbH Utility Blood Coagulation Modulators 

Invention Significance There continues to be a need for safe and effective 

To avoid hemolysis during sample collection and transfer to the sample tube, the needle size should be chosen to suit the animal and collection site, and blood should be transferred to the sample tube without excessive force. Blood samples should be thoroughly mixed immediately with the anticoagulant after collection. However, samples that are mixed too vigorously can lead to red cell fragmentation and hemolysis. 

The local laboratory should always be consulted as to the appropriate anticoagulant and sample collection tubes to be used. Noncore tests may require the use of other anticoagulants. 

Lipid Source Type of extraction and separation Test system Results Reference 

PE Human brain Folch TGT, antithromboplastin test, Stypven test PE active PS inhibitory Barkhan et al. (1956) 

lecithin Brain, egg yolk Folch Thrombin generation PE active PS, PI, lecithin inactive Robinson and Poole (1956) 

PE Human brain Folch TGT PE could replace platelets in the test Garrett (1956) 

All cephalin fractions Human brain Folch (and modification) TGT, recaldfied clotting time, prothrombin conversion test PE inactive in TGT PS active in recalcified clotting time all had some activity no sin e active lipid found Biggs and Bidwell (1957) 

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The sodium salts of sulphuric acid esters of dextran are used as anticoagulants for the same purposes as heparin. 

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