Thrombopoietin Agonists in Patients With Idiopathic Thrombocytopenic Purpura

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by reduced platelet counts (<100 × 109/L) and increased bleeding risk in the absence of other causes associated with thrombocytopenia().. It affects 2-4 per 100,000 individuals annually with an overall prevalence of about 10/100,000 individuals().

Manifestations of idiopathic thrombocytopenic purpura( ITP) can be localised haemorrhaging in skin or mucous membranes that are usually of little to no clinical consequence (petechiae, purpura, ecchymoses, epistaxis); more rarely, ITP can be associated with severe bleeding events such as intracranial haemorrhage (ICH). However, most ITP patients are asymptomatic in the presence of platelet counts greater than 50x109/L2.()

Idiopathic thrombocytopenia purpura is diagnosed in absence of secondary causes of immune mediated thrombocytopenia including autoimmune diseases (systemic lupus erthematosus , antiphospholipid antibody syndrome) lymphoproliferative disorders (chronic lymphocytic leukemia ) viral infection (hepatitis c virus , human immunodeficiency virus

The goal of treatment in patients with of idiopathic thrombocytopenic purpura is to maintain the platelet count at a level that reduces the risk of bleeding with minimal treatment-related toxic effects. Observation alone is recommended when no or mild bleeding is present and the platelet count is more than 30,000 per cubic millimeter in adults.23 Treatment in patients with a lower platelet count is indicated only if bleeding occurs or if the platelet count is very low. (For example, most experts would treat a non bleeding patient who had a platelet count of <10,000 per cubic millimeter().

Historically , the treatment of idiopathic thrombocytopenia purpura has been directed at inhibiting the production of anti platelet autoantibodies or opsonization of antibody coated platelets. However, impaired platelet production is increasingly recongnized as a contributor to thrombocytopenia in patients with idiopathic thrombocytopenia purpura.

New treatment guidelines have supported a shift from corticosteroids and splenectomy to newer medical treatments that mitigate the thrombocytopenia and avoid splenectomy. The thrombopoietin receptor agonists (TPO-RA), romiplostim, eltrombopag, and avatrombopag, have markedly altered the treatment of ITP()

Thrombopoietin (TPO) is the main cytokine that stimulates thrombopoiesis, and although platelet counts are low in ITP patients, no compensatory increase in TPO production occurs in these patients().

Thrombopoietin receptor agonists (TPO-RAs) are TPO mimetics that can bind to and activate TPO receptors, leading to megakaryocyte maturation, proliferation and differentiation and resulting in increased platelet production. Two major TPO-RAs, romiplostim and eltrombopag, have been investigated in several randomized controlled trials (RCTs) involving adult and pediatric ITP patients the results of which are encouraging. Currently, romiplostim and eltrombopag are recommended as second-line therapeutic options for adult ITP patients().