Increased procoagulant activity of red blood cells in the presence of cisplatin.
BACKGROUND
Cisplatin based chemotherapy is a well recognized risk factor for coagulation disorders and thrombosis. The pathophysiological mechanisms by which cisplatin promote thrombosis are not well understood.


METHODS
Red blood cells (RBCs) were separated from peripheral blood of patients with breast cancer (n = 10) and healthy adults (n = 6) and treated with cisplatin. Coagulation time of RBCs was assessed by one step recalcification time and the productions of thrombin, intrinsic and extrinsic factor Xa were measured in the presence or absence of various concentrations of lactadherin. Exposed phosphatidylserine was stained with lactadherin and observed by confocal microscopy and flow cytometry.


RESULTS
Neither fresh RBCs nor RBCs treated without cisplatin had potent procoagulant activity. Cisplatin treatment increased procoagulant activity of RBCs in a cell number- and concentration-dependent manner. Exposed phosphatidylserine was stained with lactadherin and after cisplatin treatment, strong fluorescence was revealed by confocal microscopy. Lactadherin bound RBCs from patients with breast cancer increased from (1.9 +/- 0.5)% on control RBCs to (68.0 +/- 3.5)% on RBCs treated with 10 micromol/L cisplatin for 24 hours.


CONCLUSIONS
Cisplatin treatment increases procoagulant activity of RBCs, which have a strong association with exposure of phosphatidylserine. The increased procoagulant activity may contribute to the pathogenesis of thrombophilia during cisplatin based chemotherapy in breast cancer patients.
Lü
Cheng-fang
CF
Department of Hematology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Yu
Hong-juan
HJ
Hou
Jin-xiao
JX
Zhou
Jin
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D002945:Cisplatin / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques
D000970:Antineoplastic Agents; D002945:Cisplatin