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

Abstract

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-Endothelialand prothrombotic (Annexin V ϩ ) 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 1ϩ2 ) 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.

Vertebral Artery Occlusion After Chemotherapy

“…[1][2][3][5][6][7] In agreement with all the referred authors, it is concluded that once a vascular event has occurred, discontinuation of cisplatinbased chemotherapy is mandatory. 8 In this case cisplatin was changed for carboplatin.…”

“…Vascular events have been described as a rare complication in relation to anticancer drugs. 4 Specifically, some authors have reported events in relation to cisplatin, [1][2][3][5][6][7] as well as to the combination of cisplatin, etoposide, and bleomycin. 2,5,6 We have not found any other case in literature of occlusion of a big cerebral artery induced by chemotherapy.…”

“…1 The role of tumors as risk factors for vascular disorders has long been established. However, there is little evidence regarding the effects of chemotherapy.…”

Response to Letter by García Martín et al

“…3 The levels of circulating prothrombotic MPs were high, with 741 endothelial-derived MPs/L, and 2373 platelet-derived MPs/L, (compared with mean 460 and 1023 MPs/L in controls with cancer). High levels of thrombin-antithrombin complex (6.0 g/L, normal values 1.0 to 4.1 g/L) and fragments F 1ϩ2 of prothrombine (2.6 nmol/L, normal values 0.4 to 1.1 nmol/L) were found 3 days after the stroke.…”

“…2 We recently postulated a mechanism of direct endothelial cell lesion induced by cisplatin, with release of prothrombotic fragments of endothelial cell in the circulation, causing further platelet and coagulation activation. 3 We demonstrated that cisplatin induces in patients with cancer a rapid and brief decrease in the level of circulating endothelial or platelet-derived microparticles (MPs), followed by an increase of these MPs with successive cisplatin infusions. 3 These bimodal kinetics may be consecutive to a brief increase in MPs clearance by liver Kupfer cells activated by cisplatin, followed by a longer phase of procoagulant MP release due to endothelial cell death or apoptosis.…”