Anti-thrombotic therapy

Despite these uncertainties, there seems to be a general tendency in the reported studies to support the hypothesis that low doses of aspirin may be more effective in anti-thrombotic therapy than the conventional doses. As mentioned, the results of these studies vary somewhat in terms of definite recommendations of the lowest, clinically useful dose of the drug for prevention of thrombosis, possibly due to the factors discussed above. Perhaps an even better solution would be to use long intervals between doses preferably the drug should not be given more often than... 

Thus, in view of the complexity of the pharmacology of aspirin, and the fact that it acts on a step common to PGIj and TXAj biosynthesis, a better approach in anti-thrombotic therapy might be to employ inhibitors specific for the thromboxane. synthetase. As has already been discussed in this chapter, a large number of such inhibitors have been found. The most promising of these are derivatives of imidazole [121,122], such as 1-n-butyl-imidazole [124] and 4-[2-(lH-imidazole-l-yl)ethoxy]ben-zoic acid hydrochloride (UK 37248) [131,132]. 

There was an increased risk of seizures in patients with a previous history of seizures and in association with anti-neoplastic therapy (97). Patients with thrombotic thrombocytopenic purpura also appear to be at greater risk of seizures during contrast examination. Fatal status epilep-ticus can occur during CT (98). The non-ionic agent iopa-midol appears to be less likely to cause seizures (76). 

Epidemiologic studies have indicated a very strong inverse association between HDL-cholesterol levels and the incidence of arteriosclerotic cardiovascular disease [32]. HDL is thought to promote efflux of cholesterol from peripheral cells in the vascular wall and return of that cholesterol to the liver for excretion in bile, a process known as reverse cholesterol transport [21]. HDL has also been shown to have anti-inflammatory and anti-thrombotic activities [21]. Therefore, HDL levels may influence both the hyperlipidemia and inflammatory processes proposed as factors in the development of atherosclerosis. Although clinical data in support of HDL-raising are limited, in the VA-HIT trial gemfibrozil therapy in men with coronary artery disease and low HDL-cholesterol modestly increased HDL levels and reduced coronary events by 22% [33]. Presently, other methods of effectively and safely increasing HDL-cholesterol levels have not been discovered. 

Prothrombin complex concentrates are available in three main types the most effective are four-factor concentrates containing factors II, VII, IX, and X. Three-factor concentrates (mainly in use in the USA) lack factor VII and are less effective in reversing oral anticoagulation therapy. The third type consists of activated products, such as factor VIII inhibitor bypassing activity (FEIBA) these products are not indicated for reversal of oral anticoagulation, but they are indicated for treatment of inhibitors (anti-factor VIII antibodies) in patients with hemophilia A [31 ]. FEIBA is associated with thrombotic events [67 ]. 

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