Article

Mechanisms of response to treatment in autoimmune thrombocytopenic purpura.

University of Washington Seattle, Seattle, Washington, United States
New England Journal of Medicine (Impact Factor: 54.42). 05/1989; 320(15):974-80. DOI: 10.1056/NEJM198904133201505
Source: PubMed

ABSTRACT To determine the mechanisms of an increase in the platelet count after therapy for autoimmune thrombocytopenic purpura, we determined the survival time and localization of radiolabeled autologous platelets and measured platelet-associated immunoglobulin levels before and after prednisone therapy or splenectomy in 19 patients with the disease. Eleven of 12 patients (92 percent) responded to prednisone with a mean threefold increase in the platelet count, resulting from increased platelet production (P less than 0.005); platelet survival was unchanged. Treatment with steroids failed in only one patient, whose pretreatment platelet production was already above normal. After splenectomy, 6 of 10 patients had a mean fourfold rise in the platelet count that correlated with increased platelet survival (P less than 0.005), together with improved platelet recovery (the percentage of platelets circulating in the blood immediately after the injection). Platelet production was unchanged. Base-line 111In-labeled platelet localization in the liver was normal in five patients in whom splenectomy was effective and increased to above normal in two of three in whom it was ineffective. Total platelet localization in the liver and spleen decreased by more than half after successful splenectomy (P less than 0.001), whereas it decreased by less than 25 percent after unsuccessful splenectomy. Platelet-associated immunoglobulin levels neither predicted nor correlated with treatment responses to prednisone or splenectomy. We conclude that prednisone improves platelet counts primarily by increasing platelet production, whereas the effect of splenectomy is to prolong platelet survival. Baseline measurements of platelet turnover and of platelet localization in the liver may be helpful in predicting the response to prednisone or splenectomy, respectively.

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    • "Clinical response of ITP patients to therapy that inhibits phagocytosis The importance of platelet destruction in ITP is further supported by the demonstration that splenectomy results in a complete, unmaintained remission in about two-thirds of ITP patients (Branehog, 1975; Gernsheimer et al, 1989; Louwes et al, 2001). In addition, agents such as intravenous IgG, anti- D and corticosteroids, which work, in part, by interfering with phagocytosis, may result in a temporary normalization of the platelet count (Cines & McMillan, 2005). "
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    • "However, there is now substantial evidence indicating that impaired thrombopoiesis contributes to the thrombocytopenia of ITP. In the late 1980s, studies of platelet kinetics using radiolabelled autologous (instead of allogeneic) platelet transfusions indicated that platelet survival in ITP was longer than previously thought (up to 3 d), and that turnover or production of new platelets was not increased (Stoll et al, 1985; Ballem et al, 1987; Gernsheimer et al, 1989). In support of this, ultrastructural studies of the bone marrow revealed that megakaryocytes are often damaged and apoptotic in ITP, and patient plasma containing antiplatelet antibodies inhibits megakaryocyte differentiation in vitro (Chang et al, 2003; Houwerzijl et al, 2004). "
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    • "However, in the early 1980s, the survival time of circulating autologous platelets in several studies using 111-indium showed that platelet survival was longer than expected (near normal). Therefore platelet turnover, and by inference platelet production, was found either to be decreased or at best normal in approximately two-thirds of patients with ITP (Heyns et al, 1982, 1986; Stoll et al, 1985; Ballem et al, 1987; Gernsheimer et al, 1989). This finding is presumed to be due to a direct effect of antibody on megakaryocyte maturation or platelet release. "
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