Variable Effects of Radiological Contrast Media on Thrombus Growth in a Rabbit Jugular Vein Thrombosis Model

Levi, M; Biemond, Bart J.; Sturk, Auguste; Hoek, J A; Cate, J. W. Ten

doi:10.1055/s-0038-1646393

Cited by 18 publications

(5 citation statements)

References 20 publications

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“…Nevertheless, several lines of evidence suggest that true differences in thrombotic risk exist between contrast agents. Using a rabbit jugular vein thrombosis model, Levi et al demonstrated that ionic contrast agents were associated with less thrombus growth than nonionic contrast agents (27). In this study, % thrombus growth in 3 h was approximately 15% and 35% in animals receiving ioxaglate (low osmolar ionic) and ioxithalamate (high osmolar ionic), respectively, compared to approximately 100% in animals receiving the nonionic agent, iopamidol.…”

Section: Discussionmentioning

confidence: 52%

Effects of Radiographic Contrast Agents on Thrombin Formation and Activity

Fay

Parker²

1998

Thromb Haemost

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SummaryClinical trials suggest that the risk of thrombosis during coronary angioplasty is lower with ionic contrast agents than with nonionic contrast agents. However, the molecular mechanisms underlying this effect are unknown. This study examined the effects of contrast agents on thrombin formation and its interaction with substrates, inhibitors, and ligands to define potential mechanisms by which contrast agents affect thrombus formation. Two ionic agents, diatrizoate and ioxaglate, and one nonionic agent, ioversol, were studied. Ionic agents inhibited factor X activation by the tissue factor-factor VIIa complex more potently than ioversol (53 ± 3.7, 43.0 ± 1.9, and 26.5 ± 2.4% inhibition by diatrizoate, ioxaglate, and ioversol, respectively, at concentrations of 5%). Ionic contrast agents were potent inhibitors of prothrombinase function, inhibiting thrombin formation by >75% at contrast concentrations of 0.6% (p <0.005). Ioversol inhibited prothrombinase to a significantly lesser extent than ionic agents. Clotting assays suggested that ioxaglate was the most potent inhibitor of thrombin generation in plasma despite having the least effect on fibrin polymerization. Contrast agents inhibited binding of thrombin to fibrin, with ionic agents producing a more potent effect than ioversol (p <0.02). However, contrast agents did not inhibit thrombin-mediated platelet activation, had only a minor effect on inhibition of thrombin by antithrombin III, and did not affect thrombin-hirudin interactions. In summary, these studies identify specific mechanisms by which radiographic contrast agents inhibit thrombin formation and function – i.e. inhibition of tissue factor-dependent factor Xa generation, inhibition of the prothrombinase complex, and inhibition of thrombin binding to fibrin. These findings may help to explain the reduced risk of thrombosis during coronary angioplasty associated with ionic contrast agents.

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Section: Discussionmentioning

confidence: 52%

Effects of Radiographic Contrast Agents on Thrombin Formation and Activity

Fay

Parker²

1998

Thromb Haemost

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“…In a rabbit jugular vein thrombosis model, the injection of a non-ionic CM surprisingly provoked an increase in thrombus growth in comparison to the saline control. Significant inhibition of thrombus growth was observed with ionic CM [31]. In a canine model of arterial injury resulting from balloon dilatation.…”

Section: Experimental Thrombosis Modelsmentioning

confidence: 93%

Thrombotic risk associated with the use of iodinated contrast media in interventional cardiology: pathophysiology and clinical aspects

Idée

Corot

1999

Fundamemntal Clinical Pharma

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A review of the current knowledge of the anti-thrombotic properties of iodinated contrast media (CM) has been conducted. CM are classified according to their chemical structure, either ionic or non-ionic (monomeric or dimeric). Numerous in vitro and in vivo data show that, although all CM have anti-coagulant properties, ionic molecules are more potent than non-ionic and, furthermore, do not activate resting platelets, unlike non-ionic agents. These properties may lead to a decrease in thrombus formation during interventional procedures. Several clinical trials have shown that CM may play a role in the occurrence of acute thrombotic complications but also in delayed ischaemic events during interventional procedures. A recent meta-analysis showed that, compared to non-ionic monomers, ionic low-osmolar CM reduce the rate of coronary artery abrupt closure, but no significant difference was found with respect to ischaemic complications. Ionic CM lead to a lower deposit of thrombotic materials on catheters and guide-wires. To date, clinical data comparing ionic CM and non-ionic dimers are scarce, significantly heterogeneous and, unlike experimental data, they do not show differences between both classes of CM. Further studies are required to better understand the precise mechanisms of such interactions and to analyse the effect of CM when new antiplatelet agents or new procedures (stenting) are used, to comply with new clinical strategies.

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“…Other studies have failed to demonstrate an increased inci dence of thrombosis during venography [421 or changes in plasminogen or antiplasmin lev els [43] when iohexol was used as the contrast agent. Although there are no previous studies of the effects of iothalamate on clot structure, investigations of other high osmolar, ionic contrast agents, such as diatrizoate [5,43] and ioxitalamate [2] have demonstrated inhibi tion of fibrin polymerization [5], inhibition of thrombus growth [2] and inhibition of platelet aggregation [5], The preservation of force development at concentrations of iohexol adequate to inhibit collagen-induced aggregation is intriguing. Collagen is an indirect agonist of platelet ag gregation.…”

Section: Discussionmentioning

confidence: 99%

“…Radiographie contrast media have been re ported to alter coagulation, fibrinolysis and platelet function [1], Ionic agents have sig nificant anticoagulant effects [2]. Nonionic agents have less anticoagulant properties, and coronary artery thromboembolic events have been reported in association with their use [3,4].…”

Section: Introductionmentioning

confidence: 99%

Effects of Ionic and Nonionic Contrast Media on Clot Structure, Platelet Function and Thrombolysis Mediated by Tissue Plasminogen Activator in Plasma Clots

Carr

Carr²,

Merten³

1995

Pathophysiol Haemos Thromb

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Various radiographic contrast agents have anticoagulant or prothrombotic properties. Ionic agents are reported to have greater antithrombotic potential while nonionic agents are considered more thrombogenic. Some agents alter fibrin structure and bind to platelets in purified systems. This study compared the effects of iohexol, a nonionic agent, and iothalamate, an ionic agent, on fibrin assembly, clot structure, platelet function and clot dissolution in plasma. Plasma gels containing increasing concentrations of iothalamate were composed of thinner fibers with decreased fiber mass/ length ratios (μ) and reduced gel turbidity. Such clots were more rigid and more resistant to fibrinolysis induced by tissue plasminogen activator (tPA). Gel elastic modula increased from 10,000 to 27,000 dyn/cm² as iothalamate concentration increased from 0 to 20 mM. 50% lysis time increased from 800 to 1,250 s with the addition of 10 mM iothalamate. At 20 mM, iothalamate had no effect on ADP-induced platelet aggregation but prolonged the lag phase seen with collagen-induced aggregation. Platelet force development increased from 15,300 to 20,400 dyn with 20 m_M iothalamate. The effects of iohexol were similar. Gel optical density dropped from 0.50 to 0.32, μ fell from 3.3 to 2.2 × 10¹³ D/cm, and elastic modulus rose from 11,000 to 24,000 dyn/cm² as iohexol concentration was increased from 0 to 20 mM. Clots formed in the presence of 60 mM iohexol and tPA did not dissolve in 72 h while control clot 50% lysis time was 450 s. At concentrations ≥ 40 mM, iohexol completely blocked collagen-induced platelet aggregation. Platelet force development increased from 7,660 to 19,600 with 40 mM iohexol. Contrast media possess profound fibrin-altering activities in plasma. Fibrin formed in the presence of some agents may be significantly more resistant to fibrinolysis.

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Variable Effects of Radiological Contrast Media on Thrombus Growth in a Rabbit Jugular Vein Thrombosis Model

Cited by 18 publications

References 20 publications

Effects of Radiographic Contrast Agents on Thrombin Formation and Activity

Effects of Radiographic Contrast Agents on Thrombin Formation and Activity

Thrombotic risk associated with the use of iodinated contrast media in interventional cardiology: pathophysiology and clinical aspects

Effects of Ionic and Nonionic Contrast Media on Clot Structure, Platelet Function and Thrombolysis Mediated by Tissue Plasminogen Activator in Plasma Clots

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