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Rapid recovery of platelet count following administration of liposome-encapsulated clodronate in a mouse model of immune thrombocytopenia

Authors :
Nico van Rooijen
Carolina Rubel
Marina S. Palermo
Carmen Stanganelli
Juana Cabrera
Fernanda Alves-Rosa
Martín A. Isturiz
Dora Cymberknop
Silvia Vanzulli
Source :
British Journal of Haematology. 116:357-366
Publication Year :
2002
Publisher :
Wiley, 2002.

Abstract

Summary. Immune thrombocytopenic purpura (ITP) is a haematological disorder characterized by increased platelet consumption. The destruction of platelets is mediated by the reticulo-endothelial system (RES), particularly by splenic and hepatic macrophages. Previously, we demonstrated in a mouse model of thrombocytopenia that the depletion of these cells by liposome-encapsulated clodronate (LIP-CLOD) induces the recovery of the platelet count. We now report that LIP-CLOD is capable of reversing the thrombocytopenia with minimal effects on both, functional RES integrity and platelet functionality. Our data indicate that thrombocytopenic mice treated with low doses of LIP-CLOD/body weight increase the platelet count to haemostatically safe values within 18 h of treatment. The predictable bleeding time was significantly decreased in these mice, suggesting that the circulating platelets have enhanced haemostatic capacity. Platelet functionality measured through the ADP-induced fibrinogen-binding assay showed normal platelet activation after treatment. Regarding immunological competence, mice treated with LIP-CLOD showed similar antibody titres against sheep red blood cells. However, antibody-dependent cell-mediated cytotoxicity carried out by splenocytes was reduced. All these data demonstrate that LIP-CLOD deserves consideration as a potential therapeutic approach in thrombocytopenic states in which the rapid increase of platelet count is the primary goal.

Details

ISSN :
00071048
Volume :
116
Database :
OpenAIRE
Journal :
British Journal of Haematology
Accession number :
edsair.doi...........2ac1c7acb6788d8a6488f27da0e6d6aa