Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production

Abstract

SummaryChronic 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 lymphocytemediated 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.

Fostamatinib for Persistent/Chronic Adult Immune Thrombocytopenia

“…The best demonstrated targets of the autoimmune response in ITP are certain glycoproteins (GP) on the surface of platelets ( Figure 1) [9]. Primary ITP has no known underlying causes; in contrast secondary ITP, by definition, has a number of clear precipitating factors, such as lymphoproliferative disease, common variable immunodeficiency, chronic viral and bacterial infections (i.e., hepatitis C, human immune deficiency virus, cytomegalovirus and Helicobacter pylori), and many drugs, including quinine or quinidine, heparin, penicillin, nonsteroidal anti-inflammatory drugs, anticonvulsants, antirheumatic and oral antidiabetic agents.…”

A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia

“…21 Because romiplostim and eltrombopag bind to different sites on the TPO-R and the 2 molecules have not yet been directly compared, the relevance of switching from one TPO-RA to the other in clinical practice has not been A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia Mehdi Khellaf, 1 Jean-François Viallard, 2 Mohamed Hamidou, 3 Stéphane Cheze, 4 Françoise Roudot-Thoraval, 5 François Lefrere, 6 Olivier Fain, 7 Sylvain Audia, 8 Jean-François Abgrall, 9 Jean-Marie Michot, 10 Charles Dauriac, 11 Sophie Lefort, 12 Emmanuel Gyan, 13 Mathilde Niault, 14 Jean-Marc Durand, 15 Laetitia Languille, 1 David Boutboul, 16 Philippe Bierling, 17 Marc Michel, 1 and Bertrand Godeau…”

“…[1][2][3][4][5][6] ITP pathophysiology has long been considered to be only a matter of accelerated platelet destruction by platelet-bound antibodies but there is strong evidence to show that it is also associated with impaired platelet production. [7][8][9][10][11] Most therapies commonly used to treat ITP (e.g. corticosteroids, intravenous immunoglobulins (IVIg), immunosuppressants and splenectomy) are mainly active by reducing the destruction of antibody-coated platelets.…”

Is ITP a thrombophilic disorder?

“…Currently, ITP is considered the hallmark of acquired bleeding disorders. Its pathogenesis has been clarified by demonstrating its autoimmune origin, with autoantibody against platelet membrane Gp IIb/IIIa and Gp Ib causing platelet destruction [3] and insufficient compensatory platelet production [4], thus resulting in decreased platelet count. Primary ITP, in which no underlying disease is evident, has an annual incidence of 1.6-3.2 cases per 100,000 adults.…”