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