Low platelet counts alone do not cause bleeding in an experimental immune thrombocytopenic purpura in mice

Abstract

BACKGROUND AND OBJECTIVES: The physiopathogenesis of hemorrhagic phenomena in patients with autoimmune thrombocytopenic purpura is associated with low platelet levels. In the present work the relation between thrombocytopenia and bleeding was examined. The possible participation of endothelial cells in bleeding was also investigated. DESIGN AND METHODS: Immune thrombocytopenia and bleeding were studied in mice injected with anti-mouse and anti-human platelet polyclonal rabbit IgG. Platelet levels were measured at different times and bleeding signs were systematically recorded. ANOVA tests were used to compare platelet levels. Binding of anti-platelet antibodies to vascular endothelial cells was analyzed by immunohistochemistry. RESULTS: Three different doses of anti-platelet IgG caused the same low platelet levels, but bleeding occurred only with high doses of anti-platelet IgG irrespective of the platelet levels. No inflammation around blood vessels was observed in paraffin-embedded tissue sections of organs. Immunohistochemistry demonstrated anti-platelet antibodies bound to vascular endothelium. INTERPRETATION AND CONCLUSIONS: We showed lack of correlation between platelet counts and bleeding in a murine model. The binding of anti-platelet IgG to endothelial cells of small vessels is an indication that antibody-mediated endothelial activation, in addition to thrombocytopenia, could be participating in bleeding.