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Journal of Thrombosis and Haemostasis :... Mar 2015The burden of severe bleeding in adults and children with immune thrombocytopenia (ITP) has not been established. (Review)
Review
BACKGROUND
The burden of severe bleeding in adults and children with immune thrombocytopenia (ITP) has not been established.
OBJECTIVES
To describe the frequency and severity of bleeding events in patients with ITP, and the methods used to measure bleeding in ITP studies.
PATIENTS/METHODS
We performed a systematic review of all prospective ITP studies that enrolled 20 or more patients. Two reviewers searched Medline, Embase, CINAHL and the Cochrane registry up to May 2014. Overall weighted proportions were estimated using a random effects model. Measurement properties of bleeding assessment tools were evaluated.
RESULTS
We identified 118 studies that reported bleeding (n = 10 908 patients). Weighted proportions for intracerebral hemorrhage (ICH) were 1.4% for adults (95% confidence interval [CI], 0.9-2.1%) and 0.4% for children (95% CI, 0.2-0.7%; P < 0.01), most of whom had chronic ITP. The weighted proportion for severe (non-ICH) bleeding was 9.6% for adults (95% CI, 4.1-17.1%) and 20.2% for children (95% CI, 10.0-32.9%; P < 0.01) with newly-diagnosed or chronic ITP. Methods of reporting and definitions of severe bleeding were highly variable in primary studies. Two bleeding assessment tools (Buchanan 2002 for children; Page 2007 for adults) demonstrated adequate inter-rater reliability and validity in independent assessments.
CONCLUSIONS
ICH was more common in adults and tended to occur during chronic ITP; other severe bleeds were more common in children and occurred at all stages of disease. Reporting of non-ICH bleeding was variable across studies. Further attention to ITP-specific bleeding measurement in clinical trials is needed to improve standardization of this important outcome for patients.
Topics: Adult; Age Factors; Cerebral Hemorrhage; Child; Hemorrhage; Humans; Platelet Count; Predictive Value of Tests; Prognosis; Purpura, Thrombocytopenic, Idiopathic; Risk Assessment; Risk Factors; Severity of Illness Index
PubMed: 25495497
DOI: 10.1111/jth.12813 -
The Journal of International Medical... Oct 2020We reviewed relevant research on rituximab (RTX) treatment for pediatric immune thrombocytopenia (ITP) to elucidate the efficacy and safety of RTX. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We reviewed relevant research on rituximab (RTX) treatment for pediatric immune thrombocytopenia (ITP) to elucidate the efficacy and safety of RTX.
METHODS
Prospective clinical trials of RTX for the treatment of pediatric ITP were collected by searching the PubMed, Cochrane Library, Web of Science, and OVID: EMBASE databases and ClinicalTrials.gov. We examined rates of overall response (OR), complete response (CR), partial response (PR), sustained response (SR), relapse (R), and adverse drug reaction (ADR). The Methodological Index for Nonrandomized Studies scale was used, and sensitivity analyses were performed.
RESULTS
For five studies, including 100 patients, the pooled OR, CR, PR, SR, R, and ADR rates were 52% (95% CI: 0.36-0.77, = 78%), 52% (95% CI: 0.41-0.67, = 45%), 18% (95% CI: 0.10-0.33, = 33%), 43% (95% CI: 0.29-0.63, = 0%), 25% (95% CI: 0.06-0.96, = 52%), and 30% (95% CI: 0.15-0.58, = 64%), respectively.
CONCLUSION
There is evidence, albeit low quality, that RTX may be a better second-line therapy than splenectomy for children with ITP; however, its efficacy and safety need to be validated by further high-quality clinical trials, such as randomized controlled trials.
Topics: Child; Humans; Minors; Prospective Studies; Purpura, Thrombocytopenic, Idiopathic; Rituximab; Thrombocytopenia
PubMed: 33115308
DOI: 10.1177/0300060520962348 -
American Journal of Kidney Diseases :... Feb 2009Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are related conditions with similar clinical features of variable severity. The objective... (Review)
Review
BACKGROUND
Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are related conditions with similar clinical features of variable severity. The objective of this systematic review is to evaluate the benefits and harms of available interventions for HUS and TTP.
SELECTION CRITERIA FOR STUDIES
MEDLINE (1966 to June 2006), EMBASE (1980 to June 2006), the Cochrane Central Register, conference proceedings, and reference lists were searched to find randomized controlled trials (RCTs) of any intervention for HUS or TTP in patients of all ages selected for inclusion for this systematic review.
INTERVENTIONS
Trials that compared an intervention with placebo, an intervention with supportive therapy, or one or more different interventions for HUS or TTP.
OUTCOMES
For TTP trials, failure of remission at 2 weeks or less and at 1 month or longer, all-cause mortality rate, and relapse rate. For HUS trials, all-cause mortality, chronic reduced kidney function, and persistent proteinuria or hypertension at last follow-up.
RESULTS
For TTP in adults, we found 6 RCTs of 331 patients. Two trials compared plasma infusion with plasma exchange using fresh frozen plasma and showed failure of remission at 2 weeks (2 trials, 140 patients; relative risk, 2.87; 95% confidence interval, 1.41 to 5.84), and all-cause mortality (relative risk, 1.91; 95% confidence interval, 1.09 to 3.33) occurred more frequently in the plasma infusion group. Three trials compared plasma exchange using cryosupernatant plasma with plasma exchange using fresh frozen plasma, and a meta-analysis of these trials showed no difference. Seven RCTs in 476 young children with postdiarrheal HUS have been conducted. None of the evaluated interventions (fresh frozen plasma transfusion, heparin with or without urokinase or dipyridamole, Shiga toxin-binding protein, and steroid) were superior to supportive therapy alone for any outcomes.
LIMITATIONS
Limitations of this review include the small number and suboptimal quality of reporting of included trials, possibility of publication bias, small number of participants with atypical HUS, and failure to report results for patients with atypical and typical HUS separately.
CONCLUSIONS
No additional therapy has been shown to increase efficacy over plasma exchange for TTP. No intervention has been shown to be superior to supportive therapy in patients with postdiarrheal HUS.
Topics: Hemolytic-Uremic Syndrome; Humans; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Randomized Controlled Trials as Topic
PubMed: 18950913
DOI: 10.1053/j.ajkd.2008.07.038 -
The Journal of Pediatrics Apr 2010To determine the incidence of immune thrombocytopenic purpura (ITP) after measles-mumps-rubella (MMR) immunization compared with natural measles and rubella, its... (Review)
Review
OBJECTIVE
To determine the incidence of immune thrombocytopenic purpura (ITP) after measles-mumps-rubella (MMR) immunization compared with natural measles and rubella, its clinical course and outcome, and the risk of recurrence after repeat MMR vaccination.
STUDY DESIGN
We performed a systematic review of the Ovid MEDLINE (1950 to present) bibliographic database. We selected studies that reported cases of thrombocytopenia in a known number of children who were immunized with MMR vaccine before development of ITP. We also extracted data from the same and other studies regarding bleeding manifestations and the resolution of MMR-associated thrombocytopenia or thrombocytopenic purpura within 6 months. Finally, we studied the risk of ITP recurrence after MMR immunization or reimmunization.
RESULTS
On the basis of 12 studies, the incidence of MMR-associated ITP ranged from 0.087 to 4 (median 2.6) cases per 100,000 vaccine doses. Severe bleeding manifestations were rare, and MMR-associated thrombocytopenia resolved within 6 months from diagnosis in 93% of the children. MMR vaccination of unimmunized patients with ITP and revaccination of patients with prior ITP did not lead to recurrence of thrombocytopenia.
CONCLUSIONS
MMR-associated ITP is rare, self-limited, and non-life threatening, and susceptible children with ITP should be immunized with MMR at the recommended ages.
Topics: Humans; Incidence; Measles-Mumps-Rubella Vaccine; Practice Guidelines as Topic; Purpura, Thrombocytopenic; Risk Factors; Vaccination
PubMed: 20097358
DOI: 10.1016/j.jpeds.2009.10.015 -
Frontiers in Pharmacology 2024Treatment of glomerulonephritis presents several challenges, including limited therapeutic options, high costs, and potential adverse reactions. As a recognized Chinese... (Review)
Review
Treatment of glomerulonephritis presents several challenges, including limited therapeutic options, high costs, and potential adverse reactions. As a recognized Chinese patent medicine, poly-glycosides (TWP) have shown promising benefits in managing autoimmune diseases. To evaluate clinical effectiveness and safety of TWP in treating glomerulonephritis, we systematically searched PubMed, Cochrane Library, Web of Science, and Embase databases for controlled studies published up to 12 July 2023. We employed weighted mean difference and relative risk to analyze continuous and dichotomous outcomes. This meta-analysis included 16 studies that included primary membranous nephropathy (PMN), type 2 diabetic kidney disease (DKD), and Henoch-Schönlein purpura nephritis (HSPN). Analysis revealed that additional TWP administration improved patients' outcomes and total remission rates, reduced 24-h urine protein (24hUP) and decreased relapse events. The pooled results demonstrated the non-inferiority of TWP to glucocorticoids in achieving total remission, reducing 24hUP, and converting the phospholipase A2 receptor (PLA2R) status to negative. For DKD patients, TWP effectively reduced 24hUP levels, although it did not significantly improve the estimated glomerular filtration rate (eGFR). Compared to valsartan, TWP showed comparable improvements in 24hUP and eGFR levels. In severe cases of HSPN in children, significant clinical remission and a reduction in 24hUP levels were observed with the addition of TWP treatment. TWP did not significantly increase the incidence of adverse reactions. Therefore, TWP could offer therapeutic benefits to patients with PMN, DKD, and severe HSPN, with a minimal increase in the risk of side effects.
PubMed: 38841368
DOI: 10.3389/fphar.2024.1339153 -
Expert Opinion on Pharmacotherapy Apr 2023In this paper, we systematically review the efficacy and safety of thrombopoietin receptor agonists (TPORAs) for treatment of persistent and chronic immune... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
In this paper, we systematically review the efficacy and safety of thrombopoietin receptor agonists (TPORAs) for treatment of persistent and chronic immune thrombocytopenia (ITP) in children and adults.
METHODS
We searched PubMed, MEDLINE, ScienceDirect, Scopus, EMbase and the Cochrane Library to collect randomized controlled trials (RCTs) of TPO-RAs which including avatrombopag hetrombopag eltrombopag and romiplostim treated persistent and chronic ITP from their earliest records to February 2022.
RESULTS
We included 15 RCTs with a total of 1563 patients. There were ten trials of adults and five trials of children. The results of meta-analysis showed that in adult patients, patients treated with TPO-RAs had longer duration of platelet response, higher platelet response rate, lower use of rescue therapy, and lower incidence of bleeding events, and similar incidence of adverse events compared with placebo. Except for the incidence of any bleeding, the results in children were consistent with those in adults. The network meta-analysis of data on overall platelet response rates in adults showed that avatrombopag was more effective than eltrombopag and hetrombopag.
CONCLUSIONS
TPO-RAs has better efficacy and higher safety in the treatment of ITP. And the overall response rate of avatrombopag in adults was higher than that in eltrombopag and hetrombopag.
Topics: Humans; Adult; Child; Purpura, Thrombocytopenic, Idiopathic; Receptors, Thrombopoietin; Hydrazines; Benzoates; Hemorrhage; Recombinant Fusion Proteins
PubMed: 37010022
DOI: 10.1080/14656566.2023.2198089 -
Pediatric Dermatology Sep 2021Vulvar vitiligo (VV) and vulvar lichen sclerosus (VLS), both feature skin and mucosal hypo-/depigmentation. The aim of this study was to describe the clinical and... (Review)
Review
Vulvar vitiligo (VV) and vulvar lichen sclerosus (VLS), both feature skin and mucosal hypo-/depigmentation. The aim of this study was to describe the clinical and dermoscopic features of VV and VLS in the pediatric population, providing diagnostic clues, and to define their association. We performed a systematic literature review of the clinical and dermoscopic features of pediatric VV and VLS. An observational study was conducted on children affected by VLS associated with VV, referred to the Dermatology Unit of the Sant'Orsola Polyclinic in Bologna, Italy. Medical history, age at diagnosis, ethnicity, clinical and dermoscopic features, and symptoms were recorded for all patients. 124 cases of VLS and 10 cases of VV were reviewed. Clinical manifestations included hypo-/depigmented patches in both conditions, while ecchymosis/purpura and fissures/erosion were observed in VLS. Symptoms including pruritus, pain, or burning were reported only by VLS patients. In our study five patients with VLS associated with VV were retrieved. Clinical features included well-demarcated depigmented patches in VV and translucent areas, erythema, ecchymoses/purpura, and labial fusion in VLS. Dermoscopy showed white structureless areas with a whipped cream-like appearance, linear or dotted vessels, white chrysalis-like structures, erosion and red-purpuric blotches in VLS and reduced pigment network or pigment absence, intralesional spots of residual pigmentation and telangiectasias in VV. Symptoms were present in all patients. Both VV and VLS show hypo-/depigmented patches. In the presence of associated symptoms, possible VLS should be investigated with clinical and dermoscopic examination to achieve a prompt diagnosis.
Topics: Child; Female; Humans; Lichen Sclerosus et Atrophicus; Observational Studies as Topic; Skin; Vitiligo; Vulvar Lichen Sclerosus
PubMed: 34561885
DOI: 10.1111/pde.14771 -
Journal of the American Academy of... Oct 2008Acute hemorrhagic edema is an uncommon leukocytoclastic small-vessel vasculitis of young children. (Review)
Review
BACKGROUND
Acute hemorrhagic edema is an uncommon leukocytoclastic small-vessel vasculitis of young children.
OBJECTIVE
To determine clinical features and outcome of acute hemorrhagic edema of young children.
METHODS
Seven new cases are reported. A search of the literature revealed 287 published cases.
RESULTS
The 294 children (boys, 67%) ranged in age between 2 and 60 months (median, 11 months) and were in good general condition. In 195 children the disease developed after a simple acute infection. The exanthemata included large, round, red to purpuric plaques predominantly over the cheeks, ears, and extremities and mostly tender edema of the distal extremities, ears, and face. Involvement of body systems other than skin was rare. The children recovered spontaneously without sequelae.
LIMITATIONS
Results of this review must be viewed with an understanding of the limitations of the analysis process, which incorporated data exclusively from single case reports or case series.
CONCLUSIONS
Acute hemorrhagic edema of young children is a very benign vasculitis. Physicians might rapidly develop the skills necessary to diagnose this condition.
Topics: Biopsy; Cellulitis; Child; Child, Preschool; Diagnosis, Differential; Eosinophilia; Female; Humans; IgA Vasculitis; Infant; Male; Skin; Vasculitis, Leukocytoclastic, Cutaneous
PubMed: 18656284
DOI: 10.1016/j.jaad.2008.06.005 -
Health Technology Assessment... Oct 2004To examine the clinical effectiveness and cost-effectiveness of two alternative antiplatelet agents, clopidogrel and modified-release (MR)-dipyridamole, relative to... (Review)
Review
Clinical effectiveness and cost-effectiveness of clopidogrel and modified-release dipyridamole in the secondary prevention of occlusive vascular events: a systematic review and economic evaluation.
OBJECTIVES
To examine the clinical effectiveness and cost-effectiveness of two alternative antiplatelet agents, clopidogrel and modified-release (MR)-dipyridamole, relative to prophylactic doses of aspirin for the secondary prevention of occlusive vascular events.
DATA SOURCES
Electronic databases.
REVIEW METHODS
A total of 2906 titles and abstracts were rigorously screened and 441 studies were assessed in detail. Two RCTs were identified. For the assessment of cost-effectiveness, eight reviews were identified. The results were presented in structured tables and as a narrative summary. No additional clinical effectiveness data were presented in either of two company submissions. All economic evaluations (including accompanying models) included in the company submissions were assessed. Following this analysis, if the existing models (company or published) were not sufficient, a de novo model or modified versions of the models were developed.
RESULTS
In the CAPRIE trial the point estimate for the primary outcome, i.e. ischaemic stroke, myocardial infarction (MI) or vascular death, favoured clopidogrel over aspirin, but the boundaries of the confidence intervals raise the possibility that clopidogrel is not more beneficial than aspirin. In terms of the secondary outcomes reported, there was a non-significant trend in favour of clopidogrel over aspirin but the boundaries of the confidence intervals on the relative risks all crossed unity. There was no difference in the number of patients ever reporting any bleeding disorder in the clopidogrel group compared with the aspirin group. The incidences of rash and diarrhoea were statistically significantly higher in the clopidogrel group than the aspirin group. Patients in the aspirin group had a higher incidence of indigestion/nausea/vomiting than patients in the clopidogrel group. Haematological adverse events were rare in both the clopidogrel and aspirin groups. No cases of thrombotic thrombocytopenic purpura were reported in either group. Treatment with MR-dipyridamole alone did not significantly reduce the risk of any of the primary outcomes reported in ESPS-2 compared with treatment with aspirin. ASA-MR-dipyridamole was significantly more effective than aspirin alone in patients with stroke or transient ischaemic attacks (TIAs) at reducing the outcome of stroke and marginally more effective at reducing stroke and/or death. Treatment with ASA-MR-dipyridamole did not statistically significantly reduce the risk of death compared to treatment with aspirin. The number of strokes was statistically significantly reduced in the ASA-MR-dipyridamole group compared with the MR-dipyridamole group. In terms of the other primary outcomes, stroke and/or death and death, the results favoured treatment with ASA-MR-dipyridamole but the findings were not statistically significant. There was no difference in the number of bleeding complications between the ASA-MR-dipyridamole and aspirin groups. The incidence of bleeding complications was significantly lower in the MR-dipyridamole treatment group. More patients in the MR-dipyridamole treatment groups experienced headaches compared to patients receiving treatment with aspirin alone. The York model assessed the cost-effectiveness of differing combinations of treatment strategies in four patient subgroups, under a number of different scenarios. The results of the model were sensitive to the assumptions made in the alternative scenarios, in particular the impact of therapy on non-vascular deaths.
CONCLUSIONS
Clopidogrel was marginally more effective than aspirin at reducing the risk of ischaemic stroke, MI or vascular death in patients with atherosclerotic vascular disease, however, it did not statistically significantly reduce the risk of vascular death or death from any cause compared with aspirin. There was no statistically significant difference in the number of bleeding complications experienced in the clopidogrel and aspirin groups. MR-dipyridamole in combination with aspirin was superior to aspirin alone at reducing the risk of stroke and marginally more effective at reducing the risk of stroke and/or death. Compared with treatment with MR-dipyridamole alone, MR-dipyridamole in combination with aspirin significantly reduced the risk of stroke. Treatment with MR-dipyridamole in combination with aspirin did not statistically significantly reduce the risk of death compared with aspirin. Compared with treatment with MR-dipyridamole alone, bleeding complications were statistically significantly higher in patients treated with aspirin and MR-dipyridamole in combination with aspirin. Due to the assumptions that have to be made, no conclusions could be drawn about the relative effectiveness of MR-dipyridamole, alone or in combination with aspirin, and clopidogrel from the adjusted indirect comparison. The following would apply for a cost of up to GBP20,000-40,000 per additional quality-adjusted life-year. For the stroke and TIA subgroups, ASA-MR-dipyridamole would be the most cost-effective therapy given a 2-year treatment duration as long as all patients were not left disabled by their initial (qualifying) stroke. For a lifetime treatment duration, ASA-MR-dipyridamole would be considered more cost-effective than aspirin as long as treatment effects on non-vascular deaths are not considered and all patients were not left disabled by their initial stroke. In patients left disabled by their initial stroke, aspirin is the most cost-effective therapy. Clopidogrel and MR-dipyridamole alone would not be considered cost-effective under any scenario. For the MI and peripheral arterial disease subgroups, clopidogrel would be considered cost-effective for a treatment duration of 2 years. For a lifetime treatment duration, clopidogrel would be considered more cost-effective than aspirin as long as treatment effects on non-vascular deaths are not considered. It is suggested that the combination of clopidogrel and aspirin should be evaluated for the secondary prevention of occlusive vascular events. Also randomised, direct comparisons of clopidogrel and MR-dipyridamole in combination with aspirin are required to inform the treatment of patients with a history of stroke and TIA, plus trials that compare treatment with clopidogrel and MR-dipyridamole for the secondary prevention of vascular events in patients who demonstrate a genuine intolerance to aspirin.
Topics: Aspirin; Clopidogrel; Cost-Benefit Analysis; Delayed-Action Preparations; Diarrhea; Dipyridamole; Drug Costs; Drug Eruptions; Dyspepsia; Evidence-Based Medicine; Hemorrhage; Humans; Ischemia; Models, Econometric; Nausea; Platelet Aggregation Inhibitors; Research Design; Risk Factors; Ticlopidine; Treatment Outcome; Vascular Diseases; Vomiting
PubMed: 15461876
DOI: 10.3310/hta8380 -
The Lancet. Haematology Feb 2015Rituximab is commonly used as a treatment for primary immune thrombocytopenia to induce and maintain remission. The benefit of adding rituximab to standard-of-care... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rituximab is commonly used as a treatment for primary immune thrombocytopenia to induce and maintain remission. The benefit of adding rituximab to standard-of-care treatment is uncertain.
METHODS
We did a systematic review and meta-analysis of randomised controlled trials assessing the efficacy and safety of rituximab for treatment of adults with primary immune thrombocytopenia. We searched Medline, Embase, and the Cochrane database in duplicate and independently from inception up to July 31, 2014, for relevant studies. Primary outcomes were the proportion of patients achieving a complete platelet count response and a partial platelet count response (as defined in primary studies) that was maintained until the end of follow-up. We also assessed bleeding, infection, and infusion reactions.
FINDINGS
Our database search returned 468 abstracts, of which five trials (with total of 463 patients) were eligible for analysis. No patients had splenectomy at the time of enrolment. Median follow-up was 6 months (IQR 6-12). Complete response (>100 × 10(9) platelets per L without rescue therapy) was more common with rituximab than with standard of care (weighted proportions: 46·8% vs 32·5%; relative risk [RR] 1·42, 95% CI 1·13-1·77; p=0·0020). Partial response was not significantly different between groups (57·6% vs 46·7%; RR 1·26, 95% CI 0·95-1·67; p=0·11). Rituximab was not associated with a reduction in bleeding (9·2% vs 5·2%; RR 1·34, 95% CI 0·63-2·87; p=0·44) or an increase in infections (20·1% vs 12·1%; RR 1·40, 95% CI 0·87-2·26; p=0·17).
INTERPRETATION
Rituximab can improve complete platelet count responses by 6 months in patients with immune thrombocytopenia. Evidence for sustained responses beyond 6-12 months is limited. Clinicians must consider the goals of treatment before prescribing rituximab.
FUNDING
None.
Topics: Humans; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Randomized Controlled Trials as Topic; Remission Induction; Rituximab; Standard of Care; Treatment Outcome
PubMed: 26687612
DOI: 10.1016/S2352-3026(15)00003-4