Are circulating endothelial-derived and platelet-derived microparticles a pathogenic factor in the cisplatin-induced stroke?
OBJECTIVE
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 (F(1+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.


CONCLUSIONS
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.
Periard
Daniel
D
Service of Angiology, University Hospital, Lausanne, Switzerland. Daniel.Periard@chuv.ch
Boulanger
Chantal M
CM
Eyer
Stephan
S
Amabile
Nicolas
N
Pugin
Paul
P
Gerschheimer
Christiane
C
Hayoz
Daniel
D
D000328:Adult; D000368:Aged; D017304:Annexin A5 / Q000097:blood; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets; D002945:Cisplatin / Q000009:adverse effects*; D022162:Cytoplasmic Vesicles; D004730:Endothelium, Vascular; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood; D040201:Platelet Membrane Glycoprotein IIb / Q000097:blood; D020521:Stroke / Q000097:blood / Q000139:chemically induced*
D017304:Annexin A5; D000970:Antineoplastic Agents; D015415:Biomarkers; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D040201:Platelet Membrane Glycoprotein IIb; D002945:Cisplatin