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Blood, 15 October 2000, Vol. 96, No. 8, pp. 2834-2840
IMMUNOBIOLOGY
Treatment with liposome-encapsulated clodronate as a new
strategic approach in the management of immune thrombocytopenic purpura
in a mouse model
Fernanda Alves-Rosa,
Carmen Stanganelli,
Juana Cabrera,
Nico van
Rooijen,
Marina S. Palermo, and
Martín A. Isturiz
From the División Inmunología and
Medicina Nuclear, Instituto de Investigaciones Hematológicas,
Academia Nacional de Medicina, Buenos Aires, Argentina; Department of
Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit,
Amsterdam, The Netherlands.
Immune thrombocytopenic purpura (ITP) is an autoimmune disease
related to the presence of elevated levels of platelet-associated immunoglobulin, or autoantibodies. In recent years the importance of
macrophage Fc receptors in the uptake of platelets in ITP has been
confirmed. Although in patients with ITP the platelet destruction
occurs in liver and spleen, in this present experimental mouse model
the liver was the principal organ of sequestration of sensitized
platelets. The uptake in the spleen, bone marrow, lung, and kidneys was
negligible and not different from that in control animals. In addition,
the trapped platelets did not return to circulation, and new cells
derived from the platelet-storage pool or new thrombocytogenesis were
necessary to restore the platelet count. The depletion of splenic and
hepatic murine macrophages by liposome-encapsulated clodronate
(lip-clod) was studied as a new strategy for ITP treatment. Lip-clod
inhibits, in a dose-dependent manner, the antibody-induced
thrombocytopenia. Moreover, lip-clod treatment rapidly restored (24 hours) the platelet count in thrombocytopenic animals to hematologic
safe values, and despite additional antiplatelet antiserum treatment,
mice were able to maintain this level of platelets at least up to 48 hours. The bleeding times in lip-clod-treated animals was not
different from those in controls, demonstrating that the hemostasis was
well controlled in these animals. The results presented in this study
demonstrate that lip-clod treatment can be effective in the management
of experimental ITP.
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