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Rapid recovery of platelet count following administration of liposome‐encapsulated clodronate in a mouse model of immune thrombocytopenia
Author(s) -
AlvesRosa Fernanda,
Stanganelli Carmen,
Cabrera Juana,
Cymberknop Dora,
Rubel Carolina,
Vanzulli Silvia,
Van Rooijen Nico,
Palermo Marina,
Isturiz Martín A.
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03281.x
Subject(s) - platelet , medicine , splenocyte , immune system , immunology , thrombocytopenic purpura , mean platelet volume , antibody , platelet activation , hemostasis , pharmacology
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.