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Immune Thrombocytopenia: Where Are We Now?

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Platelets in Thrombotic and Non-Thrombotic Disorders

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Abstract

This review focuses on megakaryocyte development, regulation of platelet production, and the role of thrombopoietin (TPO) in relation to thrombocytopenia and correction of thrombocytopenia in immune thrombocytopenia (ITP). It appears that molecules (antibodies) and cells (T cells) that attack platelets are also directed against megakaryocytes and, thus, ITP is characterized by not only by accelerated platelet destruction but also by inhibition of platelet production. There is also a relative TPO deficiency, meaning that correction can often be achieved by administration of TPO receptor agonists. Current understanding of the pathology of ITP is extremely complicated. It seems that T helper cells (CD4) are required, even to make antibodies to platelets. However, initial studies of plasma infusion from ITP patients into normal subjects suggested that, in 10 of 26 cases, infusion of such plasma does not result in thrombocytopenia. It is possible that, in some of these outliers, all the antiplatelet antibody is on the platelets themselves and there is no free antibody in the plasma. However, clinical experience indicates that cytotoxic and other T cells are heavily involved and that there are almost no functions (receptors, cell to cell interactions, cytokine releases) of T cells that have not been demonstrated to be abnormal in ITP. Several studies with the beta T cell receptor, demonstrating important olioclonal and clonal abnormalities, have reinforced this.

Treatment of ITP remains very complicated and uncertain after a course of steroids (even there, the choice of dexamethasone versus prednisone has not been settled). Rituximab-based treatment and use of TPO receptor agonists have strong studies favoring their use, but other studies show limited likelihood of a good response in patients. It is easier to increase the platelet count in the short term than to achieve the “Holy Grail” of a cure.

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Acknowledgments

James Bussel has received research funding from Amgen, Cangene, GSK, Genzyme, InG of America, Immunomedics, Ligand, Eisai, Shionogi, and Sysmex; has participated in advisory boards for Amgen, GSK, Ligand, Shionogi, and Eisai; and had a 1-day consultation with Portola. G.C. is on the speakers' bureau and receives honoraria from GSK

Conflict of interest

Nichola Cooper receives salary and research funding from National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) Imperial College Healthcare NHS Trust and research support from the UK ITP patient support association, The National Organization for Rare Diseases (NORD), and Pfizer and has received honoraria for speaking at educational events and consultancy work from Amgen, GSK and Novartis.

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Authors and Affiliations

  1. Imperial College, Hammersmith Hospital, Ducane Road, London, W12 0HS, UK

    Nichola Cooper M.D.

  2. Weill Medical College of Cornell University, 525 East 68th Street, P-695, New York, NY, 10021, USA

    James Bussel

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  1. Nichola Cooper M.D.
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Correspondence to James Bussel .

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Editors and Affiliations

  1. Department of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia , Perugia, Italy

    Paolo Gresele

  2. Houston Methodist Hospital , Houston, Texas, USA

    Neal S. Kleiman

  3. Bloodworks Northwest, University of Washington , Seattle, Washington, USA

    José A. Lopez

  4. Sackler Inst of Pulmonary Pharmacol, King’s College London, London, United Kingdom

    Clive P. Page

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Cooper, N., Bussel, J. (2017). Immune Thrombocytopenia: Where Are We Now?. In: Gresele, P., Kleiman, N., Lopez, J., Page, C. (eds) Platelets in Thrombotic and Non-Thrombotic Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-47462-5_50

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