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Published Online
on March 22, 2007

Stroke. 2007
Published online before print March 22, 2007, doi: 10.1161/STROKEAHA.106.479733
A more recent version of this article appeared on May 1, 2007
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Submitted on December 19, 2006
Accepted on January 2, 2007

Are Circulating Endothelial-Derived and Platelet-Derived Microparticles a Pathogenic Factor in the Cisplatin-Induced Stroke?

Daniel Periard MD*; Chantal M. Boulanger PhD; Stephan Eyer MD; Nicolas Amabile MD; Paul Pugin MD; Christiane Gerschheimer;; and Daniel Hayoz MD

From the Service of Angiology (D.P., D.H.), University Hospital, Lausanne, Switzerland; INSERM (C.M.B., N.A.), Centre de Recherche Cardiovasculaire, Hôpital Lariboisière, Paris, France; the Department of Internal Medicine (S.E.), University Hospital, Lausanne, Switzerland; the Department of Internal Medicine (P.P., D.H.), Hôpital Cantonal, Fribourg, Switzerland; and the Laboratory of Hemostasis (C.G.), University Hospital, Lausanne, Switzerland.

* To whom correspondence should be addressed. E-mail: Daniel.Periard{at}chuv.ch.

Background and Purpose--To evaluate whether cisplatin-induced stroke is mediated by vascular toxicity with release of prothrombotic endothelial and platelet-derived microparticles (MPs).

Methods--Endothelial (CD31+CD41-), platelets (CD31+CD41+) and prothrombotic (Annexin V+) circulating MPs were quantified by flow cytometry in 18 patients with cancer, before and 3 days after administration of cisplatin, and compared with 18 healthy controls. Thrombin-antithrombin complex and prothrombin fragments (F1+2) were measured as markers of the activation of the coagulation.

Results--In patients with cancer, baseline levels of circulating prothrombotic, endothelial and platelet-derived MPs were similar to healthy controls and decreased significantly after administration of cisplatin. High-baseline MPs levels were observed in 5 patients who received cisplatin for a second or third cycle. A high-baseline activation of the coagulation was observed in all patients without further increase after cisplatin infusion.

Conclusion--Cisplatin treatment is immediately followed by a decrease in circulating levels of endothelial and platelet-derived MPs. However, a transient increase in MPs is observed at the second and third infusion, and this may contribute to the cisplatin-induced stroke.


Key words: brain infarction • cancer & stroke • cisplatin • microparticles




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