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Eltrombopag and the Bcl-xL Pathway in Idiopathic Thrombocytopenic Purpura (ITP)

2014-08-27 03:22:09 | BioPortfolio

Summary

The purpose of this study is to further evaluate the effects that eltrombopag has on platelets in subjects with chronic ITP. Eltrombopag is approved by the Food and Drug Administration (FDA) for the treatment of low platelets in patients with chronic ITP. It is being further studied by GlaxoSmithKline in other conditions associated with low platelets. This research study is being done because eltrombopag has been shown to increase platelet counts in a different way than other therapies for ITP. The investigators want to further study how eltrombopag affects subjects and their platelets to determine how the study drug should best be used in ITP treatment.

Description

The Bcl-xL/Bak balance has been identified as an intrinsic mechanism that is critical in determining platelet lifespan (Mason, Cell 2007). There is evidence that Bcl-xL protein expression in megakaryocytes is regulated by TPO-mediated activation of Akt pathways mediated by Jak2 and Stat 5 (possibly by Stat 3 as well). (e.g. Kozuma et al, J Thromb Haemost 2007). Little is known about the Bcl-xL / Bak axis in patients with ITP, or the effect of TPO-R stimulation on platelet survival in patients with ITP. The TPO effect may be a result of stimulation of TPO-R signalling in megakaryocytes altering the packaging of Bcl-xl into platelets, or be a direct effect of platelet TPO-R stimulation as described above.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Idiopathic Thrombocytopenic Purpura

Intervention

Promacta (eltrombopag)

Location

Weill Cornell Medical College
New York
New York
United States
10065

Status

Recruiting

Source

Weill Medical College of Cornell University

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:22:09-0400

Clinical Trials [634 Associated Clinical Trials listed on BioPortfolio]

Clinical Evaluation of Eltrombopag in Chronic Idiopathic Thrombocytopenic Purpura (ITP)

An open-label, dose-adjustment extension study to evaluate the safety and efficacy of eltrombopag for treatment of subjects with ITP who have previously been enrolled in the eltrombopag tr...

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EXTEND (Eltrombopag Extended Dosing Study)

An open-label, dose-adjustment, extension study to evaluate the safety and efficacy of eltrombopag for the treatment of subjects with idiopathic thrombocytopenic purpura (ITP) who have pre...

Platelet Function in Idiopathic Thrombocytopenic Purpura (ITP) Patients With Eltrombopag

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Association of FcγRIIIA Polymorphism and THPO Expression With Response to Eltrombopag in Refractory ITP Patients

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PubMed Articles [823 Associated PubMed Articles listed on BioPortfolio]

Clinical presentation in thrombotic thrombocytopenic purpura: Real-world data from two Mexican institutions.

Thrombotic thrombocytopenic purpura (TTP) is a hematologic disease that can be fatal if not treated early. We aimed to describe the clinical characteristics of Mexican patients with idiopathic TTP.

A Case of Multiple Cerebral Infarction Preceding Acute Exacerbation of Idiopathic Thrombocytopenic Purpura.

Although it was suggested that idiopathic thromobocytopenic purpura (ITP) can be a paradoxical cause of cerebral infarction, previous reports indicate that cerebral infarction associated with ITP occu...

Relapsed/refractory acquired thrombotic thrombocytopenic purpura in a patient with Sjögren syndrome: Case report and review of the literature.

Thrombotic thrombocytopenic purpura (TTP) is a rare, fatal disorder which could be caused by autoimmune diseases. However, TTP secondary to Sjögren syndrome (SS) is extremely rare.

Thrombotic thrombocytopenic purpura and hemophagocytic lymphohistiocytosis in an elderly man: A case report.

Thrombotic thrombocytopenic purpura (TTP) and hemophagocytic lymphohistiocytosis (HLH) are rare hematologic conditions and have high mortality. Both TTP and HLH result from deregulation of the immune ...

Prevention of relapse in patients with acquired thrombotic thrombocytopenic purpura undergoing elective surgery: a case series.

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Medical and Biotech [MESH] Definitions

Any form of purpura in which the PLATELET COUNT is decreased. Many forms are thought to be caused by immunological mechanisms.

Thrombocytopenia occurring in the absence of toxic exposure or a disease associated with decreased platelets. It is mediated by immune mechanisms, in most cases IMMUNOGLOBULIN G autoantibodies which attach to platelets and subsequently undergo destruction by macrophages. The disease is seen in acute (affecting children) and chronic (adult) forms.

Immunoglobulin preparations used in intravenous infusion, containing primarily IMMUNOGLOBULIN G. They are used to treat a variety of diseases associated with decreased or abnormal immunoglobulin levels including pediatric AIDS; primary HYPERGAMMAGLOBULINEMIA; SCID; CYTOMEGALOVIRUS infections in transplant recipients, LYMPHOCYTIC LEUKEMIA, CHRONIC; Kawasaki syndrome, infection in neonates, and IDIOPATHIC THROMBOCYTOPENIC PURPURA.

A systemic non-thrombocytopenic purpura caused by HYPERSENSITIVITY VASCULITIS and deposition of IGA-containing IMMUNE COMPLEXES within the blood vessels throughout the body, including those in the kidney (KIDNEY GLOMERULUS). Clinical symptoms include URTICARIA; ERYTHEMA; ARTHRITIS; GASTROINTESTINAL HEMORRHAGE; and renal involvement. Most cases are seen in children after acute upper respiratory infections.

An ADAMTS protease that contains eight thrombospondin (TS) motifs. It cleaves VON WILLEBRAND FACTOR to control vWF-mediated THROMBOSIS. Mutations in the ADAMTS13 gene have been identified in familial cases of PURPURA, THROMBOTIC THROMBOCYTOPENIC and defects in ADAMTS13 activity are associated with MYOCARDIAL INFARCTION; BRAIN ISCHEMIA; PRE-ECLAMPSIA; and MALARIA.

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