Platelet kinetics in patients with idiopathic thrombocytopenic purpura and moderate thrombocytopenia

SummaryImmune thrombocytopenia (ITP) is a common autoimmune disease characterized by low platelet counts and an increased risk of bleeding. Antibody-mediated platelet destruction has been the prevailing hypothesis to explain ITP pathogenesis, supported by the efficacy of B-cell depletion therapy; however, the recent success of thrombopoietin receptor agonists lends support to the notion that platelet production is also insufficient. Best practice for the management of chronic ITP has not yet been established because data from comparative trials are lacking. Despite renewed interest in novel drugs capable of increasing platelet counts, ultimate treatment goals for ITP patients must be kept in mind: to improve patients' health and well-being. In this article, the pathophysiology of ITP is reviewed and key remaining questions about mechanism are explored. A rational approach to the management of ITP in adults is outlined, acknowledging evidence and evidence gaps, and highlighting the need for clinically important endpoints in future clinical trials.

Section: Relative Impairment In Platelet Productionmentioning

confidence: 86%

Pathophysiology and management of chronic immune thrombocytopenia: focusing on what matters

Toltl

Arnold

2010

“…Increased platelet destruction, whether immunological (ITP) or consumptive (e.g., consumptive coagulopathy, haemolytic uremia syndrome, vasculitis), was characterized by accelerated platelet turnovers with corresponding increases in megakaryocyte mass. Table I shows platelet turnover data based on autologous thrombokinetic measurements from seven studies involving 218 patients with untreated ITP (Branehog, 1975;Branehog et al, 1975;Stoll et al, 1985;du P Heyns et al, 1986;Ballem et al, 1987;Isaka et al, 1990;Louwes et al, 1999). These results showed that increased platelet production rates are uncommon in ITP patients, with most exhibiting either depressed or normal platelet production rates.…”

Section: Platelet Turnover In Itp Patientsmentioning

confidence: 99%

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

Nugent

McMillan

Nichol³

et al. 2009

237

158

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.

“…With the introduction of 111 In, a radioisotope with characteristics more suitable for the study of platelet kinetics and distribution, the small numbers of autologous platelets in ITP could be adequately labelled and total-body scintigraphy performed (Thakur et al, 1976). Using 111 In it became evident that there was considerable heterogeneity in platelet turnover between patients, with a substantial proportion having platelet production within normal limits even though the mean cell life of platelets was significantly reduced compared with that in healthy subjects (Stoll et al, 1985;Heyns et al, 1986;Ballem et al, 1987). If platelet destruction were the only mechanism to cause thrombocytopenia, then platelet production would be expected to increase to offset low platelet counts.…”

Section: Antiplatelet Autoantibodies and Their Role In The Pathogenesmentioning

confidence: 99%

ITP: a historical perspective

Stasi

Newland

2011

SummaryA clinical syndrome of bleeding and purpura consistent with a diagnosis of immune thrombocytopenia (ITP) was described by Werlhof long before platelets were identified as the cellular component of blood playing an essential role in primary haemostasis. Although a role for the spleen was suggested nearly a century ago, the pathophysiology of ITP has remained elusive for many decades. During this time Werlhof's disease was renamed idiopathic thrombocytopenic purpura, from which the acronym ITP originally derives. The second half of the 20th century brought recognition of the autoimmune components of ITP, and hence the need for a new standard nomenclature, which has recently been accepted. ITP currently stands for Immune Thrombocytopenia, a name that more appropriately reflects the low platelet count rather than purpura as the main feature of the disease, as well as to defining its underlying nature. Advances in our knowledge of the disease have paralleled the availability of new therapeutic agents, and we are now entering an era of pathophysiologically-based treatment options.