Mechanisms of response to treatment in autoimmune thrombocytopenic purpura
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). "
ABSTRACT: Chronic immune thrombocytopenia (ITP) is a haematological disorder in which patients predominantly develop skin and mucosal bleeding. Early studies suggested ITP was primarily due to immune-mediated peripheral platelet destruction. However, increasing evidence indicates that an additional component of this disorder is immune-mediated decreased platelet production that cannot keep pace with platelet destruction. Evidence for increased platelet destruction is thrombocytopenia following ITP plasma infusions in normal subjects, in vitro platelet phagocytosis, and decreased platelet survivals in ITP patients that respond to therapies that prevent in vivo platelet phagocytosis; e.g., intravenous immunoglobulin G, anti-D, corticosteroids, and splenectomy. The cause of platelet destruction in most ITP patients appears to be autoantibody-mediated. However, cytotoxic T lymphocyte-mediated platelet (and possibly megakaryocyte) lysis, may also be important. Studies supporting suppressed platelet production include: reduced platelet turnover in over 80% of ITP patients, morphological evidence of megakaryocyte damage, autoantibody-induced suppression of in vitro megakaryocytopoiesis, and increased platelet counts in most ITP patients following treatment with thrombopoietin receptor agonists. This review summarizes data that indicates that the pathogenesis of chronic ITP may be due to both immune-mediated platelet destruction and/or suppressed platelet production. The relative importance of these two mechanisms undoubtedly varies among patients.British Journal of Haematology 06/2009; 146(6):585-96. DOI:10.1111/j.1365-2141.2009.07717.x · 4.96 Impact Factor
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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). "
ABSTRACT: There is currently no consensus on how best to manage refractory immune thrombocytopenic purpura (ITP). In part, this reflects the need for individualized treatment due to the wide spectrum of patients' requirements and responsiveness to therapies. The objective of this review is to provide a clinically useful guide to current management strategies. This article suggests investigations to identify factors that may exacerbate thrombocytopenia and underlie poor therapeutic responses, and highlights emerging therapies, including the thrombopoietic agents, which are anticipated to dramatically alter the natural history of "refractory" ITP. Morbidity, mortality and heath-related quality of life are also discussed.British Journal of Haematology 07/2008; 143(1):16-26. DOI:10.1111/j.1365-2141.2008.07275.x · 4.96 Impact Factor
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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. "
ABSTRACT: Immune thrombocytopaenic purpura (ITP) is an autoimmune bleeding disease that is rarely fatal. However, in many adults treatment is unsatisfactory, with as much morbidity from the immunosuppressive effects of treatment as from bleeding. Identifying the underlying disease process should help us to identify more targeted therapies and improve not only the treatment but also the quality of life of patients with this disorder.British Journal of Haematology 06/2006; 133(4):364-74. DOI:10.1111/j.1365-2141.2006.06024.x · 4.96 Impact Factor