Cyclosporine enhances platelet procoagulant activity

Tomasiak, Marian; Rusak, Tomasz; Gacko, Marek; Stelmach, Halina

doi:10.1093/ndt/gfl836

Cited by 28 publications

(25 citation statements)

References 35 publications

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“…In our study, there was an immediate and sustained decrease in platelet phosphatidylserine expression after administration of the immunosuppressive dosage of cyclosporine. Our findings are in contrast to the findings reported in a recent study of humans, which demonstrated that cyclosporine increased platelet phosphatidylserine expression . One possible explanation for the different results is that in our study, we evaluated the effects of cyclosporine administered in vivo, whereas the previous study in humans incubated platelets with cyclosporine in vitro.…”

Section: Discussioncontrasting

confidence: 99%

“…Upon platelet activation, phosphatidylserine is exposed on platelet surface membranes and binds to prothrombin, converting prothrombin to thrombin, and enhancing secondary hemostasis . Phosphatidylserine also is expressed during apoptosis of nucleated cells .…”

Section: Discussionmentioning

confidence: 99%

“…This is due partly to the perception that cyclosporine has a more favorable adverse effect profile when compared with other immunosuppressive agents . Recent studies in humans, however, have shown that cyclosporine can alter the platelet plasma membrane, increase the thrombogenic properties of platelets, and accelerate thrombin generation . Approximately 50% of dogs with IMHA have been shown to be in a hypercoagulable state, predisposing these patients to complications such as pulmonary thromboembolism (PTE) .…”

mentioning

confidence: 99%

“…A recent pilot study performed in our laboratory using a small number of dogs found increased platelet P‐selectin expression (an adhesion protein with procoagulant and proinflammatory properties) after administration of cyclosporine . The administration of cyclosporine also has been associated with increased platelet expression of phosphatidylserine, which acts as a catalyst for thrombin generation and accelerates thrombus formation . Cyclosporine also has been shown to increase production of thromboxane A 2 in humans .…”

mentioning

confidence: 99%

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The Effects of Cyclosporine on Platelet Function and Cyclooxygenase Expression in Normal Dogs

Thomason

Lunsford

Pinchuk

et al. 2012

Veterinary Internal Medicne

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Background: Cyclosporine has been shown to alter platelet plasma membranes and have a hypercoagulable effect in humans, leading to thromboembolic complications.Hypothesis/Objectives: Our hypothesis was that by modulating platelet reactivity, cyclosporine increases the risk of thromboembolic complications. The objective was to determine the effects of cyclosporine on primary hemostasis in normal dogs.Animals: Eight healthy, intact female dogs. Methods: A repeated-measures design utilized flow cytometry to evaluate platelet expression of platelet reactivity markers (P-selectin and phosphatidylserine) and COX-1 and COX-2 during the administration of 2 cyclosporine dosages (19 mg/kg q12h [immunosuppressive dosage] and 5 mg/kg q24h [atopy dosage]). Urine 11-dehydro-thromboxane-B 2 (11-dTXB 2 ) concentration was normalized to urine creatinine concentration, and platelet function was analyzed by PFA-100.Results: After a week of the immunosuppressive dosage, all platelet reactivity markers showed a significant decrease in mean fluorescent intensity (MFI). After the atopy dosage, only P-selectin and COX-2 MFI demonstrated a change from baseline, decreasing by 29% (P = .013) and 31% (P = .003), respectively. Urinary 11-dTXB 2 -to-creatinine ratio significantly increased at all time points during the immunosuppressive dosage, but no significant change occurred during administration of the atopy dosage. PFA-100 closure times using collagen/ADP cartridges increased by 62% (P = .008) with the immunosuppressive dosage and decreased by 45% with the atopy dosage (P = .035). No significant changes in closure times occurred with collagen/epinephrine cartridges.Conclusions and Clinical Importance: Our study suggests that, similar to what is observed in humans, cyclosporine alters the platelet plasma membrane and increases thromboxane production in dogs, especially at immunosuppressive dosages.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

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The Effects of Cyclosporine on Platelet Function and Cyclooxygenase Expression in Normal Dogs

Thomason

Lunsford

Pinchuk

et al. 2012

Veterinary Internal Medicne

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“…Calcineurin inhibitors cause arteriolar vasoconstriction probably through multiple mechanisms, including upregulation of endothelin and thromboxane and downregulation of vasodilators (such as prostaglandin and nitric oxide). Increased procoagulant activity may also play a role [38][39][40]. A recent experimental study showed that cyclosporine induces increased endothelial release of complement activating microparticles suggesting that blocking complement activation may help to alleviate the condition [41 && ].…”

Section: Calcineurin Inhibitor-associated Thrombotic Microangiopathymentioning

confidence: 99%

Thrombotic microangiopathy in renal allografts

Nádasdy¹

2014

Current Opinion in Organ Transplantation

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TMA is a serious complication of renal transplantation, usually with poor outcome. However, with improving understanding of underlying pathogeneses, more effective disease-specific therapeutic interventions can be designed. Appropriate treatment depends on the correct diagnosis, which relies primarily on renal allograft biopsy. Standardization of pathologic criteria and introduction of new molecular testing methods in renal biopsy specimens hopefully will improve diagnostic accuracy.

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