Differing mechanisms of clotting inhibition by ionic and nonionic contrast agents

The anticoagulant potency of ioxaglate has been shown to be approximately twice that of iopamidol and iohexol. Those findings were obtained with use of the thrombin time as a test and platelet-poor plasma as a thrombin substrate. The authors confirmed these findings with use of a whole-blood version of the same test. However, the thrombin time measures only the final stages of the clotting process. A measure of the entire intrinsic pathway would more nearly simulate the situation in the angiographic suite. When measured with such an assay, the anticoagulant potency of ioxaglate was equivalent to that of diatrizoate and was approximately four times that of iopamidol and iohexol. Because of this difference in potency, it seemed likely that the ionic agents were inhibiting the clotting cascade at a late stage as well as at an earlier stage. To investigate this possibility, whole blood-contrast agent mixtures were activated, incubated for several minutes, and then diluted with either citrated or heparinized whole blood. There was rapid clot formation when the unclotted iopamidol and iohexol mixtures were diluted with citrated whole blood but not when they were diluted with heparinized whole blood. The ionic mixtures did not clot in the presence of either anticoagulant. Thus, in unclottable mixtures nonionic agents still permitted the generation of procoagulants. These procoagulants are theoretically capable of causing clotting on reinjection.