Reticulated platelets in the evaluation of thrombopoietic disorders

The laboratory diagnosis of immune platelet destruction has relied predominantly on the presence or absence of megakaryocytes in bone marrow. Recently, examination of peripheral blood platelets for high RNA content (reticulated platelets) or for elevated levels of platelet-associated IgG have been suggested as less invasive diagnostic tests. We used thiazole orange fluorescence labeling to determine the percentage of circulating reticulated platelets and two antibodies with different specificities directed against human IgG to measure platelet-associated IgG by flow cytometry in 59 patients with either immune thrombocytopenic purpura (n = 23) or chemotherapy-induced thrombocytopenia (n = 36). The percentage of reticulated platelets in patients with immune thrombocytopenia was significantly increased (38.6% +/- 27.4% [mean +/- 1 SD]), compared with patients receiving chemotherapy and normal subjects (7.2% +/- 3.3% and 2.9% +/- 2.2%, respectively). However, 17% of patients with immune thrombocytopenia had reticulated platelet values in the range observed for normal subjects and for patients with chemotherapy. Although one third of patients with immune thrombocytopenia had very high platelet IgG levels, the majority could not be distinguished from patients receiving chemotherapy solely on this basis. Combining the reticulated platelet determination with the IgG data did not improve the sensitivity or specificity of the reticulated platelet determination alone. We conclude that a flow cytometric assay for reticulated platelets is a better discriminant than flow-measured platelet IgG for diagnosing immune platelet destruction. We further postulate that the subset (17%) of patients with immune destruction who have relatively low percentages of reticulated platelets may represent patients with an inappropriately low thrombopoietic response.