title: An analysis of mechanisms underlying the antifibrinolytic properties of radiographic contrast agents.
abstract: BACKGROUND
  Radiographic contrast agents inhibit fibrinolysis, although by poorly defined pathways. The purpose of this study was to define specific mechanisms by which contrast agents inhibit clot lysis.
  
  
  RESULTS
  Diatrizoate (high osmolar ionic agent), ioxaglate (low osmolar ionic), and ioversol (nonionic) were studied in vitro. Diatrizoate inhibited clot lysis by 81.3+/-0.6% vs. control (p<0.001). Ioxaglate inhibited clot lysis by 41.7+/-11.9%, which was of borderline significance (p=0.07). Ioversol did not significantly inhibit clot lysis (14.9+/-11.5% decrease vs. control; p>0.3). Inhibition of fibrinolysis was not explained by the high osmolarities of contrast agents, by their iodine content, or by their effects on the amidolytic activities of t-PA, urokinase, or plasmin. However, plasminogen activation by t-PA, urokinase, or streptokinase was significantly inhibited by contrast agents. Diatrizoate, ioxaglate, and ioversol inhibited plasminogen binding to plasma clots by 51+/-4% (p<0.001), 30.1+/-4% (p<0.01), and 19.4+/-7% (p=0.07), respectively. Plasma clots formed in the presence of contrast agents were resistant to lysis by plasmin. Diatrizoate produced the most potent effect, inhibiting clot lysis by 40+/-5.7% (p<0.03). Contrast agents did not inhibit plasminogen binding to fibrin or plasmin-mediated fibrinolysis if they were added after clot formation. Contrast agents altered clot turbidity, an index of fibrin structure, if present during clot formation, but not if added to preformed clots. Contrast agents did not affect plasminogen activator inhibitor-1 or alpha(2)-antiplasmin function.
  
  
  CONCLUSIONS
  Contrast agents inhibit clot lysis by inhibiting plasminogen activation and by disrupting interactions of plasminogen and plasmin with fibrin by altering fibrin structure. Significant variation in antifibrinolytic properties exists between different contrast agents.
authors: Department of Internal Medicine (Cardiology), University of Michigan Medical School, Ann Arbor, MI 48109-0644, USA.
authors: P M
authors: PM
authors: Farrehi
authors: Y
authors: Y
authors: Zhu
authors: W P
authors: WP
authors: Fay
mesh_terms: D000933:Antifibrinolytic Agents / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D003287:Contrast Media / Q000494:pharmacology*; D003973:Diatrizoate / Q000494:pharmacology; D005337:Fibrin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D005341:Fibrinolysin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007485:Ioxaglic Acid / Q000494:pharmacology; D010958:Plasminogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D014283:Triiodobenzoic Acids / Q000494:pharmacology; D000979:alpha-2-Antiplasmin / Q000187:drug effects / Q000378:metabolism
chemical_list: D000933:Antifibrinolytic Agents; D003287:Contrast Media; D017395:Plasminogen Activator Inhibitor 1; D014283:Triiodobenzoic Acids; D000979:alpha-2-Antiplasmin; D003973:Diatrizoate; D005337:Fibrin; D010958:Plasminogen; D005341:Fibrinolysin; C054871:ioversol; D007485:Ioxaglic Acid