First Author | Alves-Rosa F | Year | 2002 |
Journal | Br J Haematol | Volume | 116 |
Issue | 2 | Pages | 357-66 |
PubMed ID | 11841439 | Mgi Jnum | J:74602 |
Mgi Id | MGI:2158859 | Citation | Alves-Rosa F, et al. (2002) Rapid recovery of platelet count following administration of liposome-encapsulated clodronate in a mouse model of immune thrombocytopenia. Br J Haematol 116(2):357-66 |
abstractText | 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. |