title: The ionic contrast medium ioxaglate interferes with thrombin-mediated feedback activation of factor V, factor VIII and platelets.
abstract: Clinical observation shows that radiographic contrast media (CM) may influence thrombus formation. In the search for the underlying mechanism, we have shown that the ionic CM ioxaglate is a potent inhibitor of thrombin generation in platelet-poor and platelet-rich plasma, whereas the influence of the non-ionic contrast medium iodixanol is minimal. Ioxaglate boosts the inhibitory effect of the platelet GPIIb/IIIa antagonist abciximab and the effects of ioxaglate and heparin are additive. Ioxaglate inhibits the clotting of fibrinogen and the activation of factors V and VIII, and of platelets by thrombin. It does not inhibit hydrolysis of small chromogenic thrombin substrates, nor does it influence the heparin-catalyzed inactivation of thrombin by antithrombin. We assume therefore that ioxaglate interferes with the binding of macromolecular substrates to the anionic exosite I of thrombin. The biological correlation to the observed antithrombotic effect of ioxaglate is then to be found in the inhibition of thrombin generation via inhibition of thrombin-mediated feedback activations.
authors.affiliation: Cardiovascular Research Institute (CARIM), Synapse BV, Maastricht University, Maastricht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Al Dieri
authors.forename: S
authors.initials: S
authors.lastname: Béguin
authors.forename: H C
authors.initials: HC
authors.lastname: Hemker
mesh_terms: D000077284:Abciximab; D000792:Angiography / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects*; D004347:Drug Interactions; D005165:Factor V / Q000378:metabolism*; D005169:Factor VIII / Q000378:metabolism*; D005246:Feedback; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D007485:Ioxaglic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D013917:Thrombin / Q000378:metabolism*; D013927:Thrombosis / Q000097:blood / Q000209:etiology
chemical_list: D000911:Antibodies, Monoclonal; D003287:Contrast Media; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D005165:Factor V; D005169:Factor VIII; D006493:Heparin; D013917:Thrombin; D000077284:Abciximab; D007485:Ioxaglic Acid