Differential effects of the iodinated contrast agents Ioxaglate, Iohexol and Iodixanol on thrombus formation and fibrinolysis.
BACKGROUND
Contrast media (CM) possess both pro-thrombotic and anticoagulant properties. Here we investigate the effect of three classes of CM; Iohexol, Iodixanol and Ioxaglate, on thrombus formation and fibrinolysis in vitro and evaluated the contribution of platelets to this process.


METHODS
Non-anticoagulated blood was mixed with CM or saline (50% or 20% (v/v)) for 1 min then citrated. Thrombi were produced in vitro under flow in a Chandler loop. Thrombus structure was visualized by immunohistochemistry using FITC-fibrin/ogen antibodies, and propidium iodide to identify nucleated blood cells. To measure fibrino/thrombolysis release of FITC-labeled fibrinogen, added prior to thrombus formation, was measured over 24 h. Platelet degranulation was analyzed by whole blood flow-cytometry.


RESULTS
No thrombi formed from blood incubated with Ioxaglate. Thrombi formed with Iohexol or Iodixanol weighed > OR = 10x more than saline controls (116+/-52 and 230+/-128 mg vs. 11+/-3 mg, respectively; p<0.0005), and were more resistant to thrombolysis as evidenced by the release of FITC over 24 h (19.1+/-8.9 and 31.9+/-17.2 U vs. 65.1+/-19.1 U, respectively; p<0.02). Thrombi formed with Iodixanol and Iohexol had larger, more diffuse platelet-rich head areas and tail regions composed of a more open fibrinogen/fibrin meshwork enclosing denser RBC rich areas compared to controls. Iodixanol and Ioxaglate did not increase platelet degranulation, but Iohexol caused a significant increase compared to the saline control (percentage of platelets expressing P-selectin 68.9+/-23.43% vs. 4.93+/-1.44%, respectively; p=0.001).


CONCLUSIONS
Thus thrombi formed with Iodixanol or Iohexol will be larger and more resistant to thrombolysis, whereas Ioxaglate may reduce the risk of thrombus formation.
Jones
Chris I
CI
The Department of Cardiac Sciences, University of Leicester, CSB Glenfield Hospital NHS Trust Groby Road, Leicester, LE3 9QP, UK. cij1@le.ac.uk
Goodall
Alison H
AH
D001792:Blood Platelets / Q000187:drug effects* / Q000473:pathology; D003287:Contrast Media / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007472:Iohexol / Q000009:adverse effects*; D007485:Ioxaglic Acid / Q000009:adverse effects*; D015539:Platelet Activation / Q000187:drug effects*; D013927:Thrombosis / Q000209:etiology* / Q000473:pathology; D014283:Triiodobenzoic Acids / Q000009:adverse effects*
D003287:Contrast Media; D014283:Triiodobenzoic Acids; D007472:Iohexol; C044834:iodixanol; D007485:Ioxaglic Acid