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

Chronic 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.

Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP.

Chronic immune thrombocytopenic purpura (ITP) is characterized by low platelet counts and mucocutaneous bleeding. In previous studies romiplostim (AMG531), a thrombopoiesis-stimulating protein, increased platelet counts in most patients with chronic ITP. This ongoing, long-term open-label, single-arm study investigated safety and efficacy in patients who completed a previous romiplostim study and had platelet counts less than or equal to 50 [corrected] x 10(9)/L.

Impact of chronic Immune Thrombocytopenic Purpura (ITP) on health-related quality of life: a conceptual model starting with the patient perspective.

Background: Immune thrombocytopenic purpura (ITP), a condition characterized by autoimmune-mediated platelet destruction and suboptimal platelet production, is associated with symptoms such as bruising, epistaxis, menorrhagia, mucosal bleeding from the gastrointestinal and urinary tracts and, rarely central nervous system bleeding. The aim of this research is to develop a conceptual model to describe the impact of ITP and its treatment on patients' health-related quality of life (HRQoL).

Methods: A literature search and focus groups with adult ITP patients were conducted to identify areas of HRQoL affected by ITP.

Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial.

Background: Chronic immune thrombocytopenic purpura (ITP) is characterised by accelerated platelet destruction and decreased platelet production. Short-term administration of the thrombopoiesis-stimulating protein, romiplostim, has been shown to increase platelet counts in most patients with chronic ITP. We assessed the long-term administration of romiplostim in splenectomised and non-splenectomised patients with ITP.

Pharmacodynamics and pharmacokinetics of AMG 531, a thrombopoiesis-stimulating peptibody, in healthy Japanese subjects: a randomized, placebo-controlled study.

AMG 531 is a novel thrombopoiesis-stimulating peptibody being investigated for the treatment of chronic immune thrombocytopenic purpura. This double-blind, phase I study evaluated the safety, pharmacodynamics, and pharmacokinetics of AMG 531 in healthy Japanese men. Thirty subjects were randomly assigned 4:1 (AMG 531/placebo) to receive 1 dose of AMG 531 (0.

Self-reported health-related quality of life in adults with chronic immune thrombocytopenic purpura.

Adult chronic immune thrombocytopenic purpura (ITP) is a disorder manifested by varying degrees of purpura and mucosal bleeding, rarely including intracranial hemorrhage. Therapy is aimed at increasing the patient's platelet count to safe levels and includes a wide variety of treatments. While the diagnosis, treatment, and prognosis of chronic ITP have been extensively discussed, the effect of ITP and its treatment on patient quality of life has not been evaluated in adults.

A disease-specific measure of health-related quality of life in adults with chronic immune thrombocytopenic purpura: psychometric testing in an open-label clinical trial.

Background: The Immune Thrombocytopenic Purpura Patient Assessment Questionnaire (ITP-PAQ) was developed to assess disease-specific quality of life (QoL) in adults with ITP. It is a 44-item questionnaire that includes scales for physical health (symptoms, fatigue/sleep, bother, and activity), emotional health (psychological and fear), overall QoL, social activity, women's reproductive health, and work. A previous study reported preliminary evidence of its reliability and validity.

A disease-specific measure of health-related quality of life for use in adults with immune thrombocytopenic purpura: its development and validation.

Background: No validated disease-specific measures are available to assess health-related quality of life (HRQoL) in adult subjects with immune thrombocytopenic purpura (ITP). Therefore, we sought to develop and validate the ITP-Patient Assessment Questionnaire (ITP-PAQ) for adult subjects with ITP.

Methods: Information from literature reviews, focus groups with subjects, and clinicians were used to develop 50 ITP-PAQ items.

An open-label, unit dose-finding study of AMG 531, a novel thrombopoiesis-stimulating peptibody, in patients with immune thrombocytopenic purpura.

Abstract The objective of this open label, phase 1-2, multicentre trial was to evaluate the safety of AMG 531, a novel thrombopoiesis-stimulating peptibody, and its effect on platelet counts in adults with immune thrombocytopenic purpura. Four patients were assigned to each of four unit-dose cohorts: 30, 100, 300 or 500 microg, administered subcutaneously on days 1 and 15 (or day 22 if the day 15 platelet count was >50 x 10(9)/l). Safety was assessed by adverse event (AE) monitoring, clinical laboratory studies and antibody assays.

AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP.

Background: Most current treatments for chronic immune thrombocytopenic purpura (ITP) act by decreasing platelet destruction. In a phase 1-2 study, we administered a thrombopoiesis-stimulating protein, AMG 531, to patients with ITP.

Methods: In phase 1, 24 patients who had received at least one treatment for ITP were assigned to escalating-dose cohorts of 4 patients each and given two identical doses of AMG 531 (0.

AMG 531: an investigational thrombopoiesis-stimulating peptibody.

Thrombopoietin (TPO) regulates megakaryopoiesis and the generation of platelets. Recombinant TPO has been investigated in clinical studies for use in thrombocytopenia with limited success. A new peptibody, AMG 531, has been shown to increase platelet counts in preclinical and Phase 1 and Phase 2 studies and to be generally safe and tolerable in those studies.

Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand.

Objective: The objective of this study was to evaluate the tolerability, pharmacodynamics, and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand, after a single intravenous or subcutaneous injection in healthy subjects.

Methods: This was a first-in-human randomized, double-blind, placebo-controlled study with 48 subjects. Six subjects in each cohort were sequentially randomized in a 2:1 ratio to receive a single injection of AMG 531 or placebo.

Prospective screening of 205 patients with ITP, including diagnosis, serological markers, and the relationship between platelet counts, endogenous thrombopoietin, and circulating antithrombopoietin antibodies.

Immune thrombocytopenia purpura (ITP) is characterized by destruction of circulating platelets and the presence of antiplatelet antibodies. Many of the current immunomodulatory therapies act by reducing platelet destruction and usually do not have a lasting effect. This prospective, exploratory study characterized patients with ITP by identifying their demographic and comorbid clinical factors, use of treatments, serologic markers of autoimmunity, and possible relationships between platelet counts, concentrations of endogenous thrombopoietin (eTPO), and the presence of circulating anti-TPO antibodies.