Treatment Of Idiopathic Thrombocytopenic Purpura Research Articles

Investigating hypercoagulability during treatment for immune‐mediated thrombocytopenia: a pilot study

Thromboembolism has recently been described as a complication following treatment for idiopathic thrombocytopenic purpura (ITP). This pilot study was undertaken to determine whether dogs suffering from ITP experience hypercoagulability during treatment and recovery. Thromboelastograms (TEG) were performed on dogs with ITP within 24 hours of admission to the hospital, the first day the platelet count exceeded 40 × 10(9) /L (Day 1), and on Days 4, 7, and 14. All dogs had hypocoagulable TEG tracings on initial admission to the hospital, but developed TEG tracings suggestive of hypercoagulability during the study period as indicated by increased maximum amplitude. Dogs with ITP developed changes on TEG consistent with hypercoagulability during the study period. Many factors are likely to contribute to these changes. The clinical risk of thrombosis in these patients is unknown.

Renal impairment, hemoglobinuria, and hemoglobinemia among patients with idiopathic thrombocytopenic purpura

Renal impairment (RI) and events potentially leading to RI were reported in idiopathic thrombocytopenic purpura (ITP) patients with specific medications. This study was conducted to estimate the incidence rate (IR) of RI, hemoglobinuria and hemoglobinemia (HE) and characterize baseline risk factors in ITP and ITP-free patients. Incident ITP and matched non-ITP patients were identified from an electronic medical record database from 1990 to 2002. ITP patients were classified by the treatment first received (initiators) or ever received (users). All cohorts were followed for study outcomes. IRs were calculated and standardized by age and gender. A total of 881 ITP and 4,496 ITP-free patients yielded 3,044 and 16,006 person-years, respectively. The ITP cohort had a slightly higher prevalence of autoimmune diseases and infections than the ITP-free cohort. The IR (/10,000 person-years) for RI, hemoglobinuria and HE was 14.2, 35.7, and 7.1 in the ITP cohort; 10.0, 48.8, and 0 in the ITP-free cohort; and 18.3, 37.1, and 6.1 in untreated ITP patients, respectively. The risk of RI, HE or hemoglobinuria was not found to differ substantially between ITP and non-ITP patients or across ITP treatments.

Primary coronary intervention for acute ST-elevation myocardial infarction in a patient with immune thrombocytopenic purpura

The ideal treatment for acute myocardial infarction in patients with idiopathic thrombocytopenic purpura (ITP) is not well-known. A 42-year-old male patient with a previous diagnosis of chronic and refractory ITP was admitted with chest pain of four-hour onset. Findings of electrocardiography was consistent with acute anteroseptal myocardial infarction. He had no risk factors for coronary heart disease and was not receiving treatment for ITP, and his platelet count varied between 11,000 and 40,000/µl before presentation, without any event of bleeding. Transthoracic echocardiography showed hypokinesia of the anterior, middle, and apical segments. Cardiac enzyme levels were elevated and platelet count was 41,000/µl. Coronary angiography revealed total occlusion of the left anterior descending artery. Primary percutaneous coronary intervention (PCI) was performed, which included predilation and stenting of the lesion. There were no bleeding or ischemic complications during or after PCI and the patient was discharged on the fifth day without any symptoms. He was instructed to take 75 mg clopidogrel daily for two weeks. He was symptom-free at a control visit after this period, with normal left ventricular wall motion on echocardiography.

Pharmacokinetics and Hepatic Uptake of Eltrombopag, a Novel Platelet-Increasing Agent

Eltrombopag (ELT) is a novel thrombopoietin receptor agonist for the treatment of idiopathic thrombocytopenic purpura. Previous reports indicate that ELT is mainly eliminated in the liver, although its pharmacokinetic profile has not yet been clarified in detail. The purpose of the present study is to investigate the overall elimination mechanism of ELT. After intravenous administration of ELT to rats, approximately 40% of unchanged ELT was excreted into the bile in 72 h, whereas less than 0.02% of the dose was excreted in urine, indicating that liver is the major elimination organ for ELT. The total clearance was much lower than the hepatic blood flow rate and comparable with hepatic uptake clearance obtained from integration plot analysis. Coadministration of rifampicin, an organic anion transporter inhibitor, reduced both total clearance and hepatic uptake clearance of ELT. These results suggest that hepatic uptake is the rate-limiting process in the overall elimination of ELT. To further characterize the uptake mechanism, uptake of ELT by freshly isolated mouse hepatocytes was examined. The ELT uptake showed concentration and energy dependence and was inhibited by various compounds, including not only organic anions but also organic cations. Hepatic uptake clearance in vivo was reduced by coadministration of an organic cation, tetrapentylammonium. Finally, uptake of ELT was observed in human embryonic kidney 293 cells transfected with human hepatic transporters organic anion-transporting polypeptide (OATP) 1B1 and OATP2B1 and organic cation transporter OCT1. These results suggest that multiple transporters, including organic anion transporters and organic cation transporters, are involved in hepatic ELT uptake.

Fournier's Gangrene in a Patient Receiving Treatment for Idiopathic Thrombocytopenic Purpura

We report the case of a 68-year-old man who was diagnosed with Fournier's gangrene (FG), which developed during immunosuppresive treatment for idiopathic thrombocytopenic purpura (ITP). The patient was administered steroids for ITP but on the 36th day, he developed FG and septic shock. We initiated antibiotic treatment and drained a periproctal abscess immediately. On day 53, extensive drainage to progressive FG and a splenectomy was performed, following which both FG and thrombocytopenia improved. This is the first case of FG has developing in a ITP patient. It appears that high-dose immunoglobulin therapy and splenectomy should be considered earlier especially for a patient complicated with FG.

Efficacy of Amifostine in Treating Patients with Idiopathic Thrombocytopenia Purpura

Idiopathic Thrombocytopenic Purpura (ITP) is an autoimmune disease characterized by the production of antibodies against platelet surface antigens, resulting in platelet destruction. ITP is generally treated using glucocorticoids, splenectomy, immunosuppressants, platelet transfusions, and also rituxan and rituximab. However, as these treatments are not effective in some refractory ITP patients, especially the elderly, who are also at greater risk of cerebral hemorrhage, we have undertaken this study to find a safe and effective way of treating these patients. In a clinical protocol, we have examined the efficacy of the cytoprotective adjuvant, amifostine, on 24 ITP patients, consisting of 21 Chinese (age: 13-92 years), and 3 Caucasians (age: 46-73 years). In order to prevent the side effects associated with amifostine treatment, an alternative dosing and anti-emetic regimen was developed as part of this protocol, which significantly improved patient acceptance. The protocol consisted of daily intravenous infusions of amifostine 5 × 400 mg per week, for a total of 4-5 weeks. All the patients experienced a long-lasting and continuing remission, defined as platelet counts greater than 100,000. Two patients relapsed: one after an upper respiratory tract infection, and another due to Helicobacter pylori. However, both these patients had complete remission, after they were treated again with amifostine. In this clinical study, we report for the first time, the successful use of amifostine for ITP treatment in refractory patients. In conclusion, amifostine may have good therapeutic effect on ITP patients, especially in refractory and/or elderly. The long-term clinical outcome and the mechanism of action of this drug still need further investigation.

Efficacy of Lower Dose Rituximab by Adding Fresh Frozen Plasma for the Treatment of Idiopathic Thrombocytopenic Purpura

AbstractAbstract 4682 OBJECTIVE:To evaluate the effectiveness and safety of lower dose rituximab by adding fresh frozen plasma in the treatment of patients with idiopathic thrombocytopenic purpura (ITP). METHODS:A prospective study was performed at Subei People,Hospital Affiliated to Yang Zhou University involving the use of lower dose rituximab combining fresh frozen plasma in 15 patients who had previously been treated with steroids, intravenous immunoglobulin (IVIG) or splenectomy. Fifteen patients with refractory ITP which were unresponsive to or relapse after the above said treatment were treated with two hundreds millilitre of fresh frozen plasma (FFP) followed with rituximab (100 mg/m2 per week for four weeks) and oral Medrol (24mg per day). Whole blood cell count in all cases and B cells of CD19 (+)/CD20 (+) were detected in eight cases before and after rituximab therapy. RESULTS:Complete response (CR) was achieved in 7 patients (46.67%), response (R) in 13(86.67%), and non-response (NR) in 2 (13.33%). The median follow-up time was 4 weeks. The median response and CR time were 7 and 14 days, respectively. CD19 (+) CD20 (+) B cells significantly decreased (P < 0.01). There were no severe adverse effects during rituximab therapy. CONCLUSION:Lower dose rituximab by adding fresh frozen plasma is effective and safe for ITP. Our therapeutic regimen is superior to other relative studies; however, a randomized control trial is needed to confirm the results of our study. Disclosures:No relevant conflicts of interest to declare.

Duration of Corticosteroid Tapering as First Line Treatment In Idiopathic Thrombocytopenic Purpura.

AbstractAbstract 3688 Background:Idiopathic Thrombocytopenic Purpura (ITP) is a relatively common benign hematologic disorder. Management of ITP is difficult as many treatment regimens present risks that may pose more harm than the disease itself. Typically, corticosteroid is used as first line treatment, but there is currently no evidence-based guideline to direct the optimal duration of therapy. Objective:To investigate the effectiveness and relative safety of various lengths of corticosteroid therapy. Methods:In a retrospective cohort study, charts of all ITP patients seen in the general hematology clinic at the London Health Sciences Centre (LHSC) from January 1, 2004 to December 31, 2009 were reviewed. Results: A total of 312 patients with ITP were reviewed. 128 of the patients (52 male, 76 female), age range 4–94 at time of diagnosis, required corticosteroid treatment. Of those, 35 patients were treated with short term steroid regimen (< 8 weeks); 32 patients had 8–16 weeks of therapy, and 64 patients received long term steroid tapering regimen (>16 weeks). Based on results, 63%, 56% and 39% of patients achieved complete response in each group respectively. The follow-up duration from diagnosis ranged from 1 month to 29 years (with median of 1 year).Duration of Corticosteroid Therapy< 8 weeks n = 358–16 weeks n = 32> 16 weeks n = 64Complete Response22 (63%)18 (56%)25 (39%)Partial Response7 (20%)7 (22%)9 (14%)No Response6 (17%)7 (22%)30 (47%)Relapse after Response12 (41%)8 (32%)17 (50%)Side Effects13 (37%)13 (41%)26 (41%)Interestingly, the same proportion of patients experienced side effects as a result of steroid use in all groups. However, frequency of serious complications such as avascular necrosis and infections, occurred at a higher rate in the long term therapy group (9%) compared to 0% in short term therapy group. Conclusions:Rapid corticosteroid taper is as effective as a slow corticosteroid taper and has less serious side effects. Disclosures:No relevant conflicts of interest to declare.

Measurement of utility values in the UK for health states related to immune thrombocytopenic purpura

Objective:To measure utility values associated with immune (idiopathic) thrombocytopenic purpura (ITP), as perceived by the United Kingdom (UK) general public.Research design and methods:A multi-step process, including clinical trial data, literature review, and patient focus group, was used to develop ITP health states valued in a web survey. Six ITP health states were defined based on platelet levels, risk of bleeding and key adverse events/disease complications. Clinical trial data on bleeding and ITP-specific quality of life data were key sources for developing health-state descriptions. 359 respondents, randomly selected from a managed web panel in the UK, completed the web-based Time Trade-Off survey. Wilcoxon signed-rank test was used to compare differences between each pair of health states.Results:Sample characteristics (mean age: 47.9 ± 16.9 years; 54% female) were comparable to the UK general population. ITP health states were valued as significantly worse than perfect health. Experiencing bleeding episodes was a more important driver than low platelet levels in valuing a health state to be worse. Substantial disutilities were associated with surviving an intracranial haemorrhage. Mean (SD) utility values for each ITP health state are: HS1: platelets ≥50 × 109/L, no outpatient bleed: 0.863 ± 0.15; HS2: platelets ≥50 × 109/L, outpatient bleed: 0.734 ± 0.19; HS3: platelets <50 × 109/L, no outpatient bleed: 0.841 ± 0.19; HS4: platelets <50 × 109/L, outpatient bleed: 0.732 ± 0.19; HS5: intracranial haemorrhage (2–6 months): 0.038 ± 0.46; HS6: steroid treatment adverse events: 0.758 ± 0.20. Potential limitations relate to web user population characteristics and lack of comparative testing of web-based TTO methods.Conclusions:Results provide evidence that the UK general population associate substantial loss of value living with ITP, suggesting an important role for new ITP treatments. Utility values based on these health states may be useful in future cost-effectiveness studies of existing and/or new ITP treatments.

Eltrombopag: A Novel Oral Thrombopoietin Receptor Agonist

To review the pharmacology and pharmacokinetics and evaluate the safety and efficacy of eltrombopag for the treatment of chronic immune (idiopathic) thrombocytopenic purpura (ITP) and thrombocytopenia associated with hepatitis C virus (HCV) cirrhosis. A Cochrane Controlled Trial Register, clinicaltrials.gov, EMBASE, and MEDLINE search was performed (January 1966-March 2010) using the key terms eltrombopag and SB-497115-GR. Searches were limited to published English-language studies in humans and a reference review of the pertinent literature was conducted. Published pharmacokinetic data and safety and efficacy trials, case reports, and case series on the use of eltrombopag were selected for inclusion. Eltrombopag is a novel second-generation thrombopoietin receptor agonist that was approved by the Food and Drug Administration for the treatment of chronic ITP in patients who had an insufficient response to corticosteroids, intravenous immune globulin, or splenectomy. Eltrombopag has been shown to be superior to placebo in increasing platelet counts, with more patients achieving counts >50 x 10(3)/microL. One study has also shown eltrombopag to be effective in the treatment of thrombocytopenia associated with HCV cirrhosis. Eltrombopag has a boxed warning related to risk of hepatotoxicity, with criteria for discontinuation in patients with elevated liver enzyme levels or clinical signs of liver damage. As such, close monitoring of laboratory parameters is required, and patients must be registered with the PROMACTA CARES program. Eltrombopag is effective in increasing platelet counts in patients with chronic ITP and in patients with HCV cirrhosis. In the treatment of ITP, eltrombopag has been studied only for short durations and is more expensive than first-line oral corticosteroids; therefore, it should be considered a second-line agent. More studies are needed to identify a place in therapy for eltrombopag in the treatment of thrombocytopenia associated with HCV cirrhosis.

Nursing of idiopathic thrombocytopenic purpura treated with laparoscopic splenectomy and open splenectomy

Objective To compare the similarities and the differences of nursing care on patients with idiopathic thrombocytopenic purpura. Underwent laparoscope splenectomy and open splenectomy. Methods A total of 122 cases admitted from October 1996 to September 2008 were selected and investigated prospectively.Among them, 72 cases were underwent laparoscope spleneetomy, the other 50 cases were accepted open splenectomy. Indexes of the recovery after operation were compared. Results The mean operation time was longer in the laparoscopic splenectomy group than that in the open group ( 135.3 min vs 108.5 min,P ＜0. 05).The laparoscopic group decreased more significantly than the open group in blood loss ( 110 ml vs 185 ml),abdominal drainage volume ( 100 ml vs 230 ml), the off-bed ambulation time(26. 2 h vs 46.9 h), the anal aerofluxus time(28.9 h vs 68. 1 h) ,food intake time(32. 2 h vs 72.3 h), and post operative hospitalization (8.5 d vs 15. 1 d). Postoperative pain was significantly less in LS group ( P ＜ 0. 05 ). There were no differences in postoperative complication, treatment effectiveness and temperature between two groups (P ＞ 0. 05 ).Conclusions Laparoscope splenectomy, whereas of less traumatic and low morbidity, results in comparable effects as open splenectomy for the treatment of idiopathic thrombocytopenic purpura.. It has important significance to know both similarities and differences of clinical nursing care for patients undergoing the two ways of splenectomy, in order to enhance the nursing quality for peri-operative patients with splenectomy via laparoscope and promote their postoperative rehabilitation. Key words: Idiopathic Thrombocytopenic Purpura; Splenectomy; Laparoscope; Nursing Care

Patients' Benefit-Risk Preferences for Chronic Idiopathic Thrombocytopenic Purpura Therapies

Idiopathic thrombocytopenic purpura (ITP) primarily is a disorder of adults characterized by autoantibody-induced platelet destruction and reduced platelet production, leading to a low peripheral blood platelet count. The long-term management of many patients with chronic ITP is unsatisfactory, largely due to the variable efficacy and risks of severe adverse effects associated with current treatment options. To estimate patients' benefit-risk preferences for treatments for ITP. Patients' adverse event risk tolerance and the levels of benefit required to offset possible risks were evaluated using choice-format conjoint analysis. Subjects chose between pairs of hypothetical treatment alternatives defined by probability of achieving safe platelet levels, need for corticosteroids, mode of administration, risk of rebound, risk of elevated liver enzyme levels, and risk of thromboembolism. In this study, we demonstrate that patients have clear and measurable benefit-risk preferences that physicians should consider when discussing treatment options with their patients. Patients were willing to accept significant risks of adverse events in return for an increase in the probability of achieving safe platelet levels, to avoid corticosteroids, and for more convenient administration. Patients were willing to accept significant risks of rebound and elevated liver enzymes for improvements in outcomes. These results demonstrate that patients with ITP are willing to accept treatment-related risks in exchange for improvements in treatment efficacy and administration attributes and suggest the importance of considering a patient's benefit-risk preferences during discussions of therapeutic options.

Evaluación semicuantitativa de glucógeno megacariocítico para el diagnóstico de púrpura trombocitopénica idiopática

El objetivo del presente estudio fue determinar semicuantitativamente glucógeno megacariocítico y los parámetros afines como ayuda al diagnóstico y tratamiento de la púrpura trombocitopénica idiopática (PTI). Las pruebas se aplicaron a 100 pacientes con diagnóstico de PTI provenientes de diversos hospitales y clínicas y en 100 sujetos aparentemente sanos, quienes dieron su consentimiento informado de acuerdo a la Declaración de Helsinki. Se investigó la presencia de glucógeno en los megacariocitos del frotis de médula ósea usando el método del ácido peryódico de Schiff y exámenes complementarios de la hemostasia: recuento de plaquetas por el método de Rees-Ecker, volumen plaquetario medio (VPM) utilizando el analizador automático Sysmex XE-2100, tiempo de protrombina, tiempo parcial de tromboplastina (TPT), tiempo de sangría, fibrinógeno, hemoglobina y recuento de glóbulos rojos por los métodos usuales. Se concluye que los pacientes con PTI presentaban disminución de glucógeno megacariocítico (100%); alteraciones en algunos de los parámetros de la coagulación como: aumento del tiempo de sangría (98%), disminución del número de plaquetas (100%); manteniéndose los tiempos de protrombina, TPT y fibrinógeno, y aumento en el VPM (88%). Además, se encontró una correlación positiva y significativa entre los valores disminuidos de plaquetas y el VPM.

Medical treatments for idiopathic thrombocytopenic purpura during pregnancy

Idiopathic thrombocytopenic purpura (ITP) is a common hematologic disorder caused by immune-mediated thrombocytopenia. The magnitude of the maternal-fetal risk of ITP during pregnancy is controversial. Labour management of pregnant women with ITP remains controversial. Management of ITP during pregnancy is complex because of the disparity between maternal and fetal platelet counts. To assess the effectiveness and safety of corticosteroids, intravenous immunoglobulin, vinca alkaloids, danazol, dapsone, and any other types of pharmacological treatments for the treatment of idiopathic thrombocytopenic purpura during pregnancy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (February 2009), LILACS (1982 to 8 February 2009), ClinicalTrials.gov (8 February 2009), Current Controlled Trials (16 February 2009), Google Scholar (16 February 2009) and ongoing and unpublished trials cited in the reference lists of relevant articles. Randomised controlled trials (RCTs) on any medical treatments for idiopathic thrombocytopenia purpura during pregnancy. Two review authors independently evaluated methodological quality and extracted trial data. Any disagreement was resolved by discussion or by consulting a third review author. This review included one RCT in which 38 women (41 pregnancies) were randomised, with only 26 women (28 pregnancies) being analysed.This RCT comparing the effect of betamethasone (1.5 mg/day) with no medication found no statistically significant difference in neonatal thrombocytopenia (risk ratio (RR) 1.12, 95% confidence interval (CI) 0.62 to 2.05) and neonatal bleeding (RR 1.00, 95% CI 0.24 to 4.13). Review authors conducted an intention-to-treat analysis which showed similar findings: RR 1.18, 95% CI 0.57 to 2.45 and RR 1.05, 95% CI 0.24 to 4.61, respectively. Maternal death, perinatal mortality, postpartum haemorrhage and neonatal intracranial haemorrhage were not studied by this RCT. Current evidence indicates that compared to no medication, betamethasone did not reduce the risk of neonatal thrombocytopenia and neonatal bleeding in ITP during pregnancy. There is insufficient evidence to support the use of betamethasone for treating ITP. This Cohrane review does not provide evidence about other medical treatments for ITP during pregnancy. This systematic review also identifies the need for well-designed, adequately powered randomised clinical trials for this medical condition during pregnancy. Unless randomised clinical trials provide evidence of a treatment effect and the trade off between potential benefits and harms are established, policy-makers, clinicians, and academics should not use betamethasone for ITP in pregnant women. Any future trials on medical treatments for treating ITP during pregnancy should test a variety of important maternal, neonatal or both outcome measures, including maternal death, perinatal mortality, postpartum haemorrhage and neonatal intracranial haemorrhage.

Lung Resection for Treatment of Idiopathic Thrombocytopenic Purpura Associated With a Pulmonary Lymphoma

Most primary lymphomas of the lung arise from the mucosa-associated lymphoid tissue of the bronchus. Autoimmune phenomena are associated with non-Hodgkin's lymphoma; among them immune thrombocytopenia is one of the most rare. In this study we report an extremely rare case of a patient with primary pulmonary mucosa-associated lymphoid tissue lymphoma associated with autoimmune thrombocytopenic purpura, with rapid restoration of normal platelet count after lung resection.

Romiplostim for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a single technology appraisal

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of romiplostim for the treatment of adults with chronic immune or idiopathic thrombocytopenic purpura (ITP) based upon a review of the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission’s evidence came from two relatively high-quality randomised controlled trials (RCTs). The ERG found no evidence that any important data were missed or that data extraction was inaccurate. In both RCTs more patients in the romiplostim than in the placebo group achieved a durable platelet response [non-splenectomised patients: romiplostim 25/41 (61%), placebo 1/21 (5%), odds ratio (OR) 24.45, 95% confidence interval (CI) 3.34 to 179.18; splenectomised patients: romiplostim 16/42 (38%), placebo 0/21 (0%), OR 8.5 (95% CI 1.15 to 372)] and an overall platelet response [non-splenectomised patients: romiplostim 36/41 (88%), placebo 3/21 (14%), OR 34.74, 95% CI 7.77 to 155.38; splenectomised patients: romiplostim 33/42 (79%), placebo 0/21 (0%), OR 16.6 (95% CI 2.37 to 706]. The difference in mean period with a platelet response was 13.9 weeks (95% CI 10.5 to 17.4) in favour of romiplostim in the RCT of non-splectomised patients and 12.1 weeks (95% CI 8.7 to 15.6) in favour of romiplostim in the RCT of splectomised patients. The manufacturer’s economic model evaluated the cost-effectiveness of romiplostim compared with standard care. The ERG had concerns about the way the decision problem was addressed in the economic model and about the non-adjustment of findings for confounding factors. In non-splenectomised patients, using romiplostim as a first option treatment, the base-case incremental cost-effectiveness ratio (ICER) was £14,840 per quality-adjusted life-year (QALY). In splenectomised patients the ICER was £14,655 per QALY. Additional sensitivity analyses performed by the ERG identified two issues of importance: whether individuals entered the model on watch and rescue or on active therapy in the comparator arm (ICER £21,674 per QALY for non-splenectomised patients, £29,771 per QALY for splenectomised patients); whether it was assumed that any unused medicine would be wasted. Combining all of the separate sensitivity analyses, and assuming that watch and rescue was not the first-line treatment, increased the ICERs further (non-splenectomised £37,290 per QALY; splenectomised £131,017 per QALY). In conclusion, the manufacturer’s submission and additional work conducted by the ERG suggest that romiplostim has short-term efficacy for the treatment of ITP, but there is no robust evidence on long-term effectiveness or cost-effectiveness of romiplostim compared with relevant comparators.

Romiplostim for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a single technology appraisal

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of romiplostim for the treatment of adults with chronic immune or idiopathic thrombocytopenic purpura (ITP) based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from two relatively high-quality randomised controlled trials (RCTs). The ERG found no evidence that any important data were missed or that data extraction was inaccurate. In both RCTs more patients in the romiplostim than in the placebo group achieved a durable platelet response [non-splenectomised patients: romiplostim 25/41 (61%), placebo 1/21 (5%), odds ratio (OR) 24.45, 95% confidence interval (CI) 3.34 to 179.18; splenectomised patients: romiplostim 16/42 (38%), placebo 0/21 (0%), OR 8.5 (95% CI 1.15 to 372)] and an overall platelet response [non-splenectomised patients: romiplostim 36/41 (88%), placebo 3/21 (14%), OR 34.74, 95% CI 7.77 to 155.38; splenectomised patients: romiplostim 33/42 (79%), placebo 0/21 (0%), OR 16.6 (95% CI 2.37 to 706]. The difference in mean period with a platelet response was 13.9 weeks (95% CI 10.5 to 17.4) in favour of romiplostim in the RCT of non-splectomised patients and 12.1 weeks (95% CI 8.7 to 15.6) in favour of romiplostim in the RCT of splectomised patients. The manufacturer's economic model evaluated the cost-effectiveness of romiplostim compared with standard care. The ERG had concerns about the way the decision problem was addressed in the economic model and about the non-adjustment of findings for confounding factors. In non-splenectomised patients, using romiplostim as a first option treatment, the base-case incremental cost-effectiveness ratio (ICER) was 14,840 pounds per quality-adjusted life-year (QALY). In splenectomised patients the ICER was 14,655 pounds per QALY. Additional sensitivity analyses performed by the ERG identified two issues of importance: whether individuals entered the model on watch and rescue or on active therapy in the comparator arm (ICER 21,674 pounds per QALY for non-splenectomised patients, 29,771 pounds per QALY for splenectomised patients); whether it was assumed that any unused medicine would be wasted. Combining all of the separate sensitivity analyses, and assuming that watch and rescue was not the first-line treatment, increased the ICERs further (non-splenectomised 37,290 pounds per QALY; splenectomised 131,017 pounds per QALY). In conclusion, the manufacturer's submission and additional work conducted by the ERG suggest that romiplostim has short-term efficacy for the treatment of ITP, but there is no robust evidence on long-term effectiveness or cost-effectiveness of romiplostim compared with relevant comparators.

Subcutaneous anti‐D treatment of idiopathic thrombocytopenic purpura in children

We investigated the effect of subcutaneous anti-D IgG as platelet enhancing therapy in children with idiopathic thrombocytopenic purpura (ITP). Twenty-three children were treated with subcutaneous anti-D 50 microg/kg. The median platelet count increased from 7 x 10(9) to 31 x 10(9)/L on day 3 (P < 0.01). The median decline in hemoglobin was 1.3 g/dl. Two children experienced minor fever and chills within 24 hr of treatment. Pain at the injection site was common but self-limiting with no effect on activity level. These results suggest subcutaneous anti-D IgG 50 microg/kg as an effective and well-tolerated treatment option in childhood ITP.

Review Article: Second-generation thrombopoietin agents for treatment of chronic idiopathic thrombocytopenic purpura in adults

To review the pharmacology, pharmacokinetics, efficacy, and safety of two new thrombopoietic (TPO) receptor agonists, romiplostim and eltrombopag, in the treatment of chronic idiopathic thrombocytopenic purpura (ITP) in adults. A MEDLINE search was conducted (1966 to March 2009) using the search terms romiplostim, AMG 531, eltrombopag, SB-497115, idiopathic thrombocytopenic purpura. Articles on phases 1-3 clinical trials in patients with ITP were identified and reviewed. References from manufacturer information, and abstracts from recent hematology meetings, were also evaluated. Controlled clinical trials evaluating romiplostim and eltrombopag for treatment of chronic ITP in adults were selected from the data sources. All published relevant abstracts were also included. Limited randomized controlled trials and open-label ongoing long-term extension studies for romiplostim and eltrombopag, have shown that both TPO agonists are effective in improving the platelet count and reducing the bleeding episodes in adult patients with ITP unresponsive to at least one standard treatment. The most common adverse events associated with the drugs are mild to moderate headaches. The use of these agents has also been associated with rare but serious side-effects including bone marrow reticulin fibrosis, thrombotic events, and myeloid malignancies. Until more long-term follow-up data regarding the safety, as well as comparative studies that further define the role of TPO agonists versus other agents in the treatment of chronic ITP are available, these agents should be reserved for patients with ITP refractory or intolerant to standard therapy.

New treatments for idiopathic thrombocytopenic purpura: rethinking old hypotheses

Background: The efficacy of thrombopoietin (TPO) mimetics in patients with idiopathic thrombocytopenic purpura (ITP) reaffirms that impaired platelet production is an important mechanism. New strategies to reduce platelet destruction, like rituximab, are also effective. Objectives: To describe the efficacy and safety of rituximab and the TPO mimetics, romiplostim and eltrombopag, and how they relate to ITP pathogenesis. Methods: Narrative review summarizing full publications and meeting abstracts. Results/conclusions: A 4-week course of rituximab is associated with a platelet count response in 60% of patients with ITP, and durable responses have been observed. Subtle increases in infection have been reported. Romiplostim and eltrombopag are each associated with a 60 – 85% response while on treatment. Transient bone marrow reticulin with romiplostim and elevated liver enzymes with eltrombopag are rare side effects. The application of these agents in non-splenectomized patients requires further study.