Thrombin generation in nonclottable mixtures of blood and nonionic contrast agents

The four newly introduced contrast agents--iopamidol, iohexol, ioversol, and ioxaglate--are of much lower osmolality than conventional agents, and claims have been made that they are substantially safer. A chromogenic assay for thrombin was applied to 1:1 (50%), 2:1 (67%), and 4:1 (80%) contrast agent-whole blood mixtures, each containing enough contrast agent to render them unclottable. Thrombin generation occurred in the nonionic-whole blood mixtures and increased with time. No thrombin could be detected in any ioxaglate-whole blood mixtures. The authors conclude that this difference presents a novel hazard in that iopamidol, iohexol, and ioversol permit thrombin generation to occur while inhibiting the fibrin polymerization step of blood coagulation, thus posing a significant, albeit theoretical, threat to patient well-being.