Prospective evaluation of the clinical usefulness of an antigen-specific assay (MAIPA) in idiopathic thrombocytopenic purpura and other immune thrombocytopenias.
TL;DR: The experience suggests that MAIPA assays are useful in the laboratory assessment of thrombocytopenia, should be performed before therapy, and that some patients with 'nonimmune' thromBocy topenia may have genuine antiplatelet antibodies.
About: This article is published in Blood.The article was published on 1996-07-01 and is currently open access. It has received 186 citations till now. The article focuses on the topics: Antigen & Thrombocytopenic purpura.
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Queen Mary University of London1, National Health Service2, University of Toronto3, Manchester Royal Infirmary4, NewYork–Presbyterian Hospital5, University of New South Wales6, Hospital of the University of Pennsylvania7, University of Washington8, Boston Children's Hospital9, Hull York Medical School10, King's College London11, St James's University Hospital12, Scripps Research Institute13, Harvard University14
TL;DR: This consensus document aims to report on new data and provide consensus-based recommendations relating to diagnosis and treatment of ITP in adults, in children, and during pregnancy.
1,902 citations
TL;DR: This review identified the need for additional studies in many key areas of the therapy of ITP such as comparative studies of "front-line" therapy for ITP, the management of serious bleeding in patients withITP, and studies that will provide guidance about which therapy should be used as salvage therapy for patients after failure of a first-line intervention.
1,601 citations
TL;DR: The authors of this up-to-date review discuss the current understanding of pathophysiology and, in particular, the way in which autoantibodies against platelets are generated.
Abstract: Immune thrombocytopenic purpura, which may lead to bleeding, is typically caused by antibodies directed against the platelet glycoprotein IIb/IIIa complex. Since the management of the disorder is different for children and adults, the authors of this up-to-date review provide separate sections on the two age groups. Along with advances in management, they also discuss the current understanding of pathophysiology and, in particular, the way in which autoantibodies against platelets are generated.
1,255 citations
Journal Article•
TL;DR: This guideline aims to assess available diagnostic tests and therapies, and attempts to provide a rational approach to the diagnosis and treatment in adults, children and in pregnancy.
Abstract: Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by persistent thrombocytopenia (peripheral blood platelet count < 150 · 10 ⁄ l) due to autoantibody binding to platelet antigen(s) causing their premature destruction by the reticuloendothelial system, and in particular the spleen (Woods et al, 1984a,b). Although the basic underlying pathophysiology of ITP has been known for 50 years (Harrington et al, 1951), the literature shows that the investigation and management of patients with thrombocytopenia vary widely, and is not evidence-based, due to a lack of clinical trials and quality research. Despite major advances in our understanding of the molecular basis of many blood disorders, the diagnosis of ITP remains one of exclusion; there are currently no robust clinical or laboratory parameters that are able to establish the diagnosis of ITP with accuracy. This guideline aims to assess available diagnostic tests and therapies, and attempts to provide a rational approach to the diagnosis and treatment in adults, children and in pregnancy. Although natural history data are becoming available (Cohen et al, 2000; Djulbegovic & Cohen, 2001; Portielje et al, 2001), there are few randomized trials in ITP and many of the recommendations, like those of the American Society of Hematology (ASH) Panel (George et al, 1996), are based on expert opinion.
711 citations
TL;DR: The recent insights into the molecular and cellular pathways that are involved in IVIG-mediated immunosuppression are covered, with a particular focus on IVIG as a therapy for IgG-dependent autoimmune diseases.
Abstract: Intravenous immunoglobulin (IVIG) preparations comprise pooled IgG antibodies from the serum of thousands of donors and were initially used as an IgG replacement therapy in immunocompromised patients. Since the discovery, more than 30 years ago, that IVIG therapy can ameliorate immune thrombocytopenia, the use of IVIG preparations has been extended to a wide range of autoimmune and inflammatory diseases. Despite the broad efficacy of IVIG therapy, its modes of action remain unclear. In this Review, we cover the recent insights into the molecular and cellular pathways that are involved in IVIG-mediated immunosuppression, with a particular focus on IVIG as a therapy for IgG-dependent autoimmune diseases.
679 citations
References
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TL;DR: A new assay is described that takes advantage of monoclonal antibodies against major platelet membrane constituents (glycoproteins IIb/IIIa and Ib and HLA class I molecule) to investigate selectively platelet reactive antibodies against epitopes on different glycoprotein.
870 citations
TL;DR: Two patients who were demonstrated to have the platelet-reducing factor prior to splenectomy still had the factor present after platelet counts had returned to normal following removal of the spleen, and the thrombocytopenic factor was found in the globulin fraction.
636 citations
TL;DR: Direct evidence is concerns direct evidence that the ITP factor destroys autologous platelets and is most likely an antibody.
Abstract: There is good evidence that a humoral factor is involved in the pathogenesis of idiopathic thrombocytopenic purpura (ITP) , for children of mothers with ITP are sometimes thrombocytopenic a t birth,' and the plasma of some patients with ITP causes thrombocytopenia when infused into normal individuals.' That the I T P humoral factor may be an antibody, is suggested by similarities between I T P and thrombocytopenia caused by heterologous antibodies in animal^,^ ' and by drug antibodies or isoantibodies in Evidence for the immune nature of I T P has remained circumstantial, however, because there has been no satisfactory immunologic technique for characterizing the factor in I T P plasma that causes thrombocytopenia in homologous recipients and no proof that the I T P factor affects autologous platelets. The present report concerns direct evidence that the ITP factor destroys autologous platelets and is most likely an antibody. Although in vitro tests for antibody were negative with the I T P plasmas used, the ITP humoral factor appeared to be species specific, was adsorbed by platelets, and was found in the 7s gamma globulin fraction of plasma. The thrombocytopenic effects of I T P plasma were found to be quantitatively, as well as qualitatively, similar to those of known antiplatelet antibodies. Studies of experimental thrombocytopenia provided information on platelet production and reserve, on mechanisms of destruction of normal and immunologically altered platelets, and on the nature of the response to splenectomy and corticosteroid therapy in ITP.
313 citations
"Prospective evaluation of the clini..." refers methods in this paper
...An improvement in sensitivity may be achieved by further modification of the assay ([I] additional antigenic targets besides GPIIbnIIa and GP Ih/IX, [2] use of a polyspecific antiglobulin rather than anti-IgG alone, and [3] use of biotin-streptavidin conjugated antibodies) or by performance of the assay early before commencement of therapy....
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...With the benefit of follow-up, we further subdivided patients with an initial diagnosis of ITP according to (1) duration of the thrombocytopenia (A < 3 months, B > 3 months) and ( 2 ) the response to immunomodulatory treatment ([ 11 never treated, [2 ] therapy induced complete remission with and without subsequent relapse, and [3 ] refractory [no increment or platelet count < 20 X 109/L)....
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TL;DR: Evidence is obtained that the IIb-IIIa complex exists in the membrane of intact nonstimulated platelets and that complex integrity is not affected by external calcium ion concentration.
310 citations
TL;DR: It is concluded that clinically adaptable assays allow detection of autoantibodies in most patients with chronic ITP, confirming the presence of an autoimmune process.
299 citations