Nonionic contrast media. Procoagulants or clotting innocents?

Compared with ionic contrast media, nonionic contrast media cause fewer adverse reactions, including hemodynamic and electrophysiologic complications, and are better tolerated by patients. However, concern as to whether nonionic agents are associated with more thromboembolic complications has been raised in recent years. This article reviews in-vitro and in-vivo coagulation studies with nonionic contrast media, including the authors' current study using blood samples from percutaneous transluminal coronary angioplasty (PTCA) patients.

Articles for this review were selected on the basis of providing viewpoints representative of both sides of the clotting controversy involving nonionic contrast media. In addition, articles were selected that, in toto, include the several relevant aspects of thrombosis during PTCA: whole blood clotting, angiography catheters, angiography syringes, rheology, and vascular endothelium. The preliminary work described used platelet adhesion/aggregation to a collagen-coated surface under controlled conditions of heparinized, whole blood flow. Adhesion/aggregation was quantified by digital analysis of real-time images obtained by epifluorescence videomicroscopy. In parallel studies, changes in markers (membrane glycoproteins) of platelet activation were measured using whole blood flow cytometry.

Although nonionic contrast media are weaker anticoagulants than ionic contrast media, no convincing evidence demonstrates that they are procoagulant. On the contrary, in-vitro studies suggest that ionic media may weaken the antithrombotic properties of vascular endothelium by direct endothelial injury. Certain clinical trials of PTCA patients substantially challenge the use of nonionics. Yet, Grabowski et al found no evidence of platelet activation by ioxaglate or iohexol in preliminary work. This result was obtained with two of the most sensitive platelet assays available: flowing whole blood aggregometry and whole blood flow cytometry. Attention should be given to the adequacy of heparinization in future clinical studies.

Nonionic contrast media are not procoagulant in vitro in the hands of most research groups. The focus of current controversy, therefore, is whether there is a clinical and in-vivo difference in thrombotic events seen with nonionic versus ionic media during PTCA. Elements in this controversy include platelet activation, blood-foreign surface (catheter and syringe) interaction, rheology, vascular endothelium, and adequacy of heparinization.