Drugs Affecting Blood Clotting

Controlled inhibition of blood clotting is a very important therapeutic strategy for prevention and treatment of heart attacks and occlusive stoke. It is usually combined with drugs to reduce blood pressure and statins to control cholesterol levels. 

Cilostazol (Pletal), a selective inhibitor of PDE III, is used for the treatment of intermittent claudication, an occlusive disease of blood vessels in the legs, which causes pain on walking. It acts as a vasodilator and inhibitor of platelet aggregation. Warfarin, initially developed as a rat poison, and a number of similar compounds, are effective anti-clotting agents by their action as vitamin K antagonists. 

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Table 34-1 Blood Clotting Factors and Drugs That Affect Them.1...

To understand how various drugs affect hemostasis, it is necessary to review the normal way in which blood clots are formed. The physiologic mechanisms involved in hemostasis are outlined in Figure 25-1, with... 

Aspirin inhibits cyclooxygenase, thus impairing platelet aggregation, This may be additive to other drugs with a similar effect and to those which affect other aspects of blood clotting. The risk of interactions and adverse effects is reduced by using a lower dose (e.g. 75mg) fortunately, a full antiplatelet effect is seen at this dose,... 

In contrast the mean concentrations of a-tocopherol in vitamin E users increased from 28 pmol/l in 1985 to 29 qmol/l in 1988, 35 pmol/l in 1991, and 56 pmol/l in 1998. Controls not taking any medications had much lower serum concentrations of a-tocopherol (7.5, 9.8,11.8, and 18.3 pg/ml). Concentrations of P-tocopherol, y- tocopherol, and 5-tocopherol in users of vitamin E were lower by up to 50% in users of vitamin E formulations. From these data the authors concluded that there is a considerable risk in the availability of over-the-counter drugs, especially those that can affect the balance between blood clotting and hemorrhage, such as salicylates and a-toco-pherol. Since women over 40 in particular tend to use so-called dietary supplements, in the belief that such products might prevent illness, and because there is unrestricted advertising in the mass media, physicians should obtain a clear medication history from their patients. 

Keys to toxicity Warfarin is a drug used to prevent blood clots in people who have had a stroke or heart attack. It is also an effective rat poison. How is this possible One key to toxicity is the dose— the amount of the chemical taken in by an organism. Exposure time can also be a factor even low-dose exposure to some chemicals over long periods of time can be hazardous. Toxicity is also affected by the presence of other chemicals in the body, the age and gender of the individual, and the chemical s ability to be absorbed and excreted. 

The finding that prostaglandins can prevent formation of blood clots has great clinical significance, because heart attacks and strokes often result ftom the formation of abnormal clots in blood vessels. An understanding of how prostaglandins affect the formation of clots may lead to the development of drugs to prevent heart attacks and strokes. 

Stoppers may contain zinc, invalidating the use of evacuated blood tubes for zinc measurement, and TBEP (tris[2-butoxyethyi] phosphate), a constituent of rubber, which may interfere with the measurement of certain drugs. With time, the vacuum in evacuated tubes is lost and their effective draw diminishes. The silicone coating also decays with age. Therefore the stock of these tubes should be rotated and careful attention paid to the expiration date. Problems with evacuated blood tubes also arise when too little blood is collected into the tubes (short draw). Although an incorrect draw is of little consequence when clotted blood is required, a disproportionate ratio of blood to anticoagulant may affect some hematology and other special tests. Therefore some tubes from each batch should be checked for volume of draw before the lot is put in use. 

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