***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . Idiopathic thrombocytopenic purpura ( ITP ) is an autoimmune disorder characterized by persistent thrombocytopenia ( peripheral blood platelet count < 150 · 10 ⁄ l ) due to autoantibody binding to platelet antigen(s ) causing their premature destruction by the reticuloendothelial system , and in particular the spleen ( Woods et al , 1984a , b ) . Although the basic underlying pathophysiology of ITP has been known for 50 years ( Harrington et al , 1951 ) , the literature shows that the investigation and management of patients with thrombocytopenia vary widely , and is not evidence -based , due to a lack of clinical trials and quality research . Despite major advances in our underst and ing of the molecular basis of many blood disorders , the diagnosis of ITP remains one of exclusion ; there are currently no robust clinical or laboratory parameters that are able to establish the diagnosis of ITP with accuracy . This guideline aims to assess available diagnostic tests and therapies , and attempts to provide a rational approach to the diagnosis and treatment in adults , children and in pregnancy . Although natural history data are becoming available ( Cohen et al , 2000 ; Djulbegovic & Cohen , 2001 ; Portielje et al , 2001 ) , there are few r and omized trials in ITP and many of the recommendations , like those of the American Society of Hematology ( ASH ) Panel ( George et al , 1996 ) , are based on expert opinion Romiplostim is a thrombopoietin receptor agonist that increases platelet counts in patients with chronic immune thrombocytopenia ( ITP ) .  Thrombopoietin receptor agonists are reported to increase the risk for reticulin fiber deposition within bone marrow . This report describes bone marrow findings from  romiplostim-treated rats , a retrospective analysis of reticulin observed in romiplostim ITP clinical trials , and a prospect i ve clinical study of the effects of romiplostim on bone marrow morphology . In rats , romiplostim produced a dose-dependent increase in bone marrow fibrosis that resolved after treatment withdrawal . Of 271 ITP patients in romiplostim clinical trials , 10 were reported to have  reticulin deposition ; reticulin grade was increased in 4 of 5 patients with both pretreatment and on-treatment bone marrow results . Reticulin grade often decreased soon after romiplostim discontinuation . In the prospect i ve study , reticulin grade during romiplostim treatment remained within the normal range for all patients and was increased in only 1 of 6 patients with pretreatment and on-treatment bone marrow results . This report suggests that romiplostim produces reversible , dose-dependent bone marrow changes in rats and produces modest increases in bone marrow reticulin in some ITP patients that decrease when therapy is discontinued . These studies were registered at www . clinical trials.gov as # NCT00102323 , # NCT00102336 , # NCT00861224 , and # NCT00116688 BACKGROUND Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of thrombocytopenia . We aim ed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period . METHODS We undertook a phase 3 , double-blind , placebo-controlled study in adults with previously treated immune thrombocytopenia of more than 6 months ' duration who had baseline platelet counts lower than 30,000 per μL. Patients were r and omly allocated ( in a 2:1 ratio ) treatment with local st and ard of care plus 50 mg eltrombopag or matching placebo once daily for 6 months . R and omisation was done central ly with a computer-generated r and omisation schedule and was stratified by baseline platelet count ( ≤ 15,000 per μL ) , use of treatment for immune thrombocytopenia , and splenectomy status . Patients , investigators , and those assessing data were masked to allocation . Dose modifications were made on the basis of platelet response . Patients were assessed for response to treatment ( defined as a platelet count of 50,000 - 400,000 per μL ) weekly during the first 6 weeks and at least once every 4 weeks thereafter ; the primary endpoint was the odds of response to eltrombopag versus placebo . Analysis was by intention to treat . This study is registered at Clinical Trials.gov , number NCT00370331 . FINDINGS Between Nov 22 , 2006 , and July 31 , 2007 , 197 patients were r and omly allocated to treatment groups and were included in the intention-to-treat analysis ( 135 eltrombopag , 62 placebo ) . 106 ( 79 % ) patients in the eltrombopag group responded to treatment at least once during the study , compared with 17 ( 28 % ) patients in the placebo group . The odds of responding were greater in patients in the eltrombopag group compared with those in the placebo group throughout the 6-month treatment period ( odds ratio 8·2 , 99 % CI 3·59 - 18·73 ; p<0·0001 ) . 37 ( 59 % ) patients receiving eltrombopag reduced concomitant treatment versus ten ( 32 % ) patients receiving placebo ( p=0·016 ) . 24 ( 18 % ) patients receiving eltrombopag needed rescue treatment compared with 25 ( 40 % ) patients receiving placebo ( p=0·001 ) . Three ( 2 % ) patients receiving eltrombopag had thromboembolic events compared with none in patients on placebo . Nine ( 7 % ) eltrombopag-treated patients and two ( 3 % ) in the placebo group had mild increases in alanine aminotransferase concentration , and five ( 4 % ) eltrombopag-treated patients ( vs none allocated to placebo ) had increases in total bilirubin . Four ( 7 % ) patients taking placebo had serious bleeding events , compared with one ( < 1 % ) patient treated with eltrombopag . INTERPRETATION Eltrombopag is effective for management of chronic immune thrombocytopenia , and could be particularly beneficial for patients who have not responded to splenectomy or previous treatment . These benefits should be balanced with the potential risks associated with eltrombopag treatment . FUNDING GlaxoSmithKline Eltrombopag ( SB-497 115 ) is a first-in-class , oral , small-molecule , nonpeptide agonist of the thrombopoietin receptor ( TpoR ) , being developed as a treatment for thrombocytopenia of various etiologies . In this phase 1 placebo-controlled clinical trial in 73 healthy male subjects , eltrombopag was administered as once-daily oral capsules for 10 days at doses of 5 , 10 , 25 , 30 , 50 , and 75 mg . The pharmacokinetics of eltrombopag were dose dependent and linear , and eltrombopag increased platelet counts in a dose-dependent manner . There were no apparent differences in the incidence or severity of adverse events in subjects receiving active or placebo study medication . These observations indicate that eltrombopag is a once-daily , oral TpoR agonist with demonstrated thrombopoietic activity in human subjects , encouraging further studies in patients with thrombocytopenia 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 ( 0.2 to 10 microg per kilogram of body weight ) . In phase 2 , 21 patients were r and omly assigned to receive six weekly subcutaneous injections of AMG 531 ( 1 , 3 , or 6 microg per kilogram ) or placebo . The primary objective was to assess the safety of AMG 531 ;  the secondary objective was to evaluate platelet counts during and after treatment . RESULTS No major adverse events that could be attributed directly to AMG 531 occurred during the treatment period ; 4 of 41 patients had transient post-treatment worsening of thrombocytopenia . In phase 1 , a platelet count that was within the targeted range ( 50,000 to 450,000 per cubic millimeter ) and at least twice the baseline count was achieved in 4 of 12 patients given 3 , 6 , or 10 mug of AMG 531 per kilogram . Overall , a platelet count of at least 50,000 per cubic millimeter was achieved in 7 of 12 patients , including 3 with counts exceeding 450,000 per cubic millimeter . Increases in the platelet count were dose-dependent ; mean peak counts were 163,000 , 309,000 , and 746,000 per cubic millimeter with 3 , 6 , and 10 microg of AMG 531 per kilogram [ corrected ] , respectively . In phase 2 , the targeted platelet range was achieved in 10 of 16 patients treated with 1 or 3 mug of AMG 531 per kilogram per week for 6 weeks . Mean peak counts were 135,000 , 241,000 , and 81,000 per cubic millimeter in the groups that received the 1-mug dose , the 3-mug dose , and placebo , respectively . CONCLUSIONS AMG 531 caused no major adverse events and increased platelet counts in patients with ITP . ( Clinical Trials.gov number , NCT00111475 [ Clinical Trials.gov ] . ) BACKGROUND Romiplostim , a thrombopoietin mimetic , increases platelet counts in patients with immune thrombocytopenia , with few adverse effects . METHODS In this open-label , 52-week study , we r and omly assigned 234 adult patients with immune thrombocytopenia , who had not undergone splenectomy , to receive the st and ard of care ( 77 patients ) or weekly subcutaneous injections of romiplostim ( 157 patients ) . Primary end points were incidences of treatment failure and splenectomy . Secondary end points included the rate of a platelet response ( a platelet count > 50 × 10(9 ) per liter at any scheduled visit ) , safety outcomes , and the quality of life . RESULTS The rate of a platelet response in the romiplostim group was 2.3 times that in the st and ard-of-care group ( 95 % confidence interval [ CI ] , 2.0 to 2.6 ; P<0.001 ) . Patients receiving romiplostim had a significantly lower incidence of treatment failure ( 18 of 157 patients [ 11 % ] ) than those receiving the st and ard of care ( 23 of 77 patients [ 30 % ] , P<0.001 ) ( odds ratio with romiplostim , 0.31 ; 95 % CI , 0.15 to 0.61 ) . Splenectomy also was performed less frequently in patients receiving romiplostim ( 14 of 157 patients [ 9 % ] ) than in those receiving the st and ard of care ( 28 of 77 patients [ 36 % ] , P<0.001 ) ( odds ratio , 0.17 ; 95 % CI , 0.08 to 0.35 ) . The romiplostim group had a lower rate of bleeding events , fewer blood transfusions , and greater improvements in the quality of life than the st and ard-of-care group . Serious adverse events occurred in 23 % of patients ( 35 of 154 ) receiving romiplostim and 37 % of patients ( 28 of 75 ) receiving the st and ard of care . CONCLUSIONS Patients treated with romiplostim  had a higher rate of a platelet response , lower incidence of treatment failure and splenectomy , less bleeding and fewer blood transfusions , and a higher quality of life than patients treated with the st and ard of care . ( Clinical Trials.gov number , NCT00415532 . ) The objective of this study was to evaluate the tolerability , pharmacodynamics , and pharmacokinetics of AMG 531 , a novel thrombopoietin receptor lig and , after a single intravenous or subcutaneous injection in healthy subjects 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 
    Output:
    
There was currently no evidence to support that TPO receptor agonists are effective in chronic ITP .
Compared to placebo or SOC , despite significantly increased platelet response , there was no evidence to demonstrate that TPO receptor agonists did improve significant bleeding events in chronic ITP .
Although long-term studies are lacking , current data demonstrated adverse effects of TPO receptor agonists were similar to that of placebo and SOC