ITP: a historical perspective

Abstract

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.

Is ITP a thrombophilic disorder?

“…In 1882, Bizzozzero identified a new independent line of cells specialized in hemostasis, and denominated these new particles "platelets" [1]. Shortly after, thrombocytopenia begun to be associated with bleeding and heterogeneous disorders characterized by low platelet count and bleeding were lumped into a new category as idiopathic thrombocytopenic purpura, a disease now reclassified with more stringent criteria under the term immune thrombocytopenia (ITP) [2].…”

“…Vascular events (any event occurring during the observation period) occurred in 6.9% of patients in the ITP cohort and in 4.0% of patients in the comparison cohort. The adjusted incidence rate ratio (IRR) of any vascular, venous, and arterial event was 1 . These findings suggested that ITP may be associated with an increased frequency in all vascular morbidities.…”

In vivo effects of eltrombopag on platelet function in immune thrombocytopenia: no evidence of platelet activation

“…1,2 Thrombopoietin receptor (TPO-R) agonists have recently been developed for the treatment of patients with ITP, and can dramatically increase platelet counts and reduce bleeding symptoms in the majority of patients, including some with severe refractory thrombocytopenia. [3][4][5] Eltrombopag, is an oral, small-molecule TPO-R agonist that interacts with the transmembrane domain of the receptor in a noncompetitive manner with endogenous TPO, thereby activating intracellular signal transduction pathways and leading to enhanced megakaryocyte differentiation, proliferation, and platelet production.…”

ITP: hematology’s Cosette from Les Misérables

“…Others have astutely summarized the intriguing history of ITP consisting of fascinating observations and game-changing discoveries, an approximate incidence of 6 per 100 000, and good paradigms for its treatment following the licensing of thrombopoietin mimetic agents. 1,2 However, any patient with leukemiasincluding chronic myeloid leukemia or even the rarer acute promyelocytic leukemiapresenting to hematology clinics in the developed world today is likely to be offered a more definitive and targeted treatment as part of a randomized clinical trial in a cooperative group than if he or she has newly diagnosed ITP. There are no collaborative clinical groups or registries for prospectively diagnosing, observing (as spontaneous remissions though rare in adults often occur in children), and treating newly diagnosed ITP patients as part of a clinical trial.…”

“…1 Histone deacetylases are a family of enzymes that remove acetyl groups from histone N-terminal tails, thereby contributing to chromatin condensation and the modulation of gene expression and of other chromatin-based processes. 2 In addition, HDACs also can deacetylate an increasing number of nonhistone proteins, impinging on diverse cellular processes.…”