The Clotting Issue: Etiologic Factors in Thromboembolism

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RATIONALE AND OBJECTIVES. The authors analyze the origins of the “clotting issue,” the controversy that began in the 1980s when contrast media, once perceived as good flushing agents for catheters because of their assumed anticoagulant properties, came under attack for allegedly causing thromboembolism. Laboratory studies as well as a number of clinical reports seemed to substantiate this charge. Nonionic agents in particular were accused by some clinicians of being more likely to cause clots to form in syringes contaminated with blood than were ionic agents. The authors wanted to determine whether some lapse in operator technique rather than a fault in the contrast agent might be to blame. The theory that the syringe and catheter materials, and not the contrast agent itself, could be the source of thromboembolic problems in angiography also is examined.

METHODS. The authors reviewed studies and reports on both sides of the issue and conducted laboratory and clinical studies of their own. For the syringe materials analysis, they used a fibrinopeptide A (FpA) enzyme-linked immunosorbent assay (ELISA) test to monitor levels as a marker of activation of coagulation. They tested catheter materials using the same technique.

RESULTS. Clots were found only in nonionic agents, but under nonclinically relevant circumstances. If the anticoagulant effect of the nonionic contrast agent was maximized by mixing rather than layering blood and agent, clots did not form. In their materials analysis, the authors demonstrated that glass syringes are thrombogenic, causing vigorous contact activation, and that plastic is less so. Polyurethane catheters are more thrombogenic, polyethylene less so. One survey conducted in the 1970s on the clinical incidence of thromboembolism in coronary angiography suggested that the single most important factor in the etiology is poor angiographic technique. The authors' studies supported their thesis.

CONCLUSIONS. In terms of the findings from laboratory studies, misinterpretation of data by nonclinicians is one problem. No evidence suggests that nonionic contrast agents are in any way prothrombotic or thrombogenic. On the contrary, in line with their greater inertness, nonionic agents have weaker effects. Ionic contrast media may cause more endothelial injury and associated localized platelet deposition than nonionic contrast media, and more anticoagulant contrast agents are more toxic. If anticoagulation is required, therefore, it should be achieved by such procedures as carefully controlled systemic heparinization rather than by resorting to more toxic materials. The activation of coagulation is caused by endothelial injury and by prolonged contact between blood and foreign surfaces such as syringes or catheters, but is inhibited by the contrast agent. Because a thrombus may form inside the catheter, whatever contrast agent is used, flushing is important.

The authors agree with the findings of one study that the incidence of thromboembolism in coronary angiography, and probably in other catheter procedures, is markedly operator dependent. The materials of the syringes and catheters used, as well as the state of the patient's intrinsic clotting, are more important factors than the contrast agent. The authors conclude that materials other than the contrast agents are the cause of thromboembolic problems; and that, being anticoagulant, contrast agents are entirely helpful, if variably so, in angiographic procedures.

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