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The Cochrane Database of Systematic... Jan 2009Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are related conditions with similar clinical features of variable severity. Survival of... (Review)
Review
BACKGROUND
Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are related conditions with similar clinical features of variable severity. Survival of patients with HUS and TTP has improved greatly over the past two decades with improved supportive care for patients with HUS and by the use of plasma exchange (PE) with fresh frozen plasma (FFP) for patients with TTP. Separate pathogenesis of these two disorders has become more evident, but management overlaps.
OBJECTIVES
To evaluate the benefits and harms of different interventions for HUS and TTP separately, in patients of all ages.
SEARCH STRATEGY
We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), conference proceedings, reference lists of articles and text books and contact with investigators were used to identify relevant studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) evaluating any interventions for HUS or TTP in patients of all ages.
DATA COLLECTION AND ANALYSIS
Three authors independently extracted data and evaluated study reporting quality using standard Cochrane criteria. Analysis was undertaken using a random effects model and results expressed as risk ratio (RR) and 95% confidence intervals (CI).
MAIN RESULTS
For TTP, we found six RCTs (331 participants) evaluating PE with FFP as the control. Interventions tested included antiplatelet therapy (APT) plus PE with FFP, FFP transfusion and PE with cryosupernatant plasma (CSP). Two studies compared plasma infusion (PI) to PE with FFP and showed a significant increase in failure of remission at two weeks (RR 1.48, 95% 1.12 to 1.96) and all-cause mortality (RR 1.91, 95% 1.09 to 3.33) in the PI group. Seven RCTs were undertaken in children with HUS. None of the assessed interventions used (FFP transfusion, heparin with or without urokinase or dipyridamole, shiga toxin binding protein and steroids) were superior to supportive therapy alone, for all-cause mortality, neurological/extrarenal events, renal biopsy changes, proteinuria or hypertension at the last follow-up visit. Bleeding was significantly higher in those receiving anticoagulation therapy compared to supportive therapy alone (RR 25.89, 95% CI 3.67 to 182.83).
AUTHORS' CONCLUSIONS
PE with FFP is still the most effective treatment available for TTP. For patients with HUS, supportive therapy including dialysis is still the most effective treatment. All studies in HUS have been conducted in the diarrhoeal form of the disease. There were no RCTs evaluating the effectiveness of any interventions on patients with atypical HUS who have a more chronic and relapsing course.
Topics: Cyclophosphamide; Hemolytic-Uremic Syndrome; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Mycophenolic Acid; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Randomized Controlled Trials as Topic
PubMed: 19160220
DOI: 10.1002/14651858.CD003595.pub2 -
Hematology, Transfusion and Cell Therapy 2023To evaluate the efficacy and safety of romiplostim (thrombopoietin-receptor agonist) in the treatment of pediatric immune thrombocytopenia (ITP). (Review)
Review
OBJECTIVE
To evaluate the efficacy and safety of romiplostim (thrombopoietin-receptor agonist) in the treatment of pediatric immune thrombocytopenia (ITP).
METHODS
Searches were conducted in MEDLINE, EMBASE, LILACS, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov (from January 2011 to August 2021). Randomized controlled trials (RCTs), double-blind, comparing romiplostim with a placebo in pediatric persistent or chronic ITP were included. The primary outcome was the overall response rate (platelets ≥ 50 × 10/L) in the absence of rescue therapy for at least two consecutive weeks. The secondary endpoints were the minimization of clinically significant bleeding and the necessity for rescue treatments and the maximization of safety (incidence of overall adverse events) and durable response (maintaining platelet counts for at least twelve weeks).
RESULTS
Two double-blind randomized placebo-controlled trials (84 participants) were included in this systematic review. Our data showed that, compared to the placebo group, the proportion of patients achieving durable platelet response was significantly higher in the romiplostim group (p = 0.003, RR = 6.34, 95%CI = 1.89 - 21.23), as was the overall response in the romiplostim group (p = 0.002, RR = 3.62, 95%CI = 1.63 - 8.03). Significant bleeding incidents (p = 0.49), overall adverse events (p = 0.71) and the need for rescue treatment (p = 0.13) were not statistically different between the romiplostim and placebo groups.
CONCLUSIONS
Romiplostim might improve both durable and overall platelet response in children and adolescents with ITP, compared to a placebo. More clinical trials are needed to evaluate the efficacy and safety of romiplostim and to compare it with other second-line treatments that are being used in pediatric ITP.
PubMed: 36273985
DOI: 10.1016/j.htct.2022.09.1275 -
Haematologica Jun 2009Eradication of H. pylori improves thrombocytopenia in some patients with immune thrombocytopenic purpura by mechanisms that remain obscure. Platelet count responses may... (Review)
Review
Eradication of H. pylori improves thrombocytopenia in some patients with immune thrombocytopenic purpura by mechanisms that remain obscure. Platelet count responses may occur independently of H. pylori infection as a result of the immune modulating effects of macrolide antimicrobials or the removal of other commensal bacteria. We performed a systematic review of the literature to determine the effect of H. pylori eradication therapy in patients with immune thrombocytopenic purpura by comparing the platelet response in patients who were, and who were not infected with H. pylori. MEDLINE, EMBASE, Cochrane central registry and abstracts from the American Society of Hematology (from 2003) were searched in duplicate and independently without language or age restrictions. Eleven studies, 8 from Japan, were included enrolling 282 patients with immune thrombocytopenic purpura who received eradication therapy; 205 were H. pylori-positive and 77 were H. pylori-negative. The odds of achieving a platelet count response following eradication therapy were 14.5 higher (95% confidence interval 4.2 to 83.0) in patients with H. pylori infection (51.2% vs. 8.8%). No study reported bleeding or quality of life. Adverse events were reported in 12 patients. H. pylori eradication therapy was of little benefit for H. pylori-negative patients. These findings strengthen the causal association between H. pylori infection and immune thrombocytopenia in some patients. Randomized trials are needed to determine the applicability of H. pylori eradication therapy across diverse geographical regions.
Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Treatment Outcome
PubMed: 19483158
DOI: 10.3324/haematol.2008.005348 -
Biomedical Reports Mar 2024Thrombopoietin receptor agonists (TPO-RAs) have a role in second-line immune thrombocytopenic purpura (ITP) treatment, binding to and activating thrombopoietin receptors...
Thrombopoietin receptor agonists use and risk of thrombotic events in patients with immune thrombocytopenic purpura: A systematic review and meta‑analysis of randomized controlled trials.
Thrombopoietin receptor agonists (TPO-RAs) have a role in second-line immune thrombocytopenic purpura (ITP) treatment, binding to and activating thrombopoietin receptors on megakaryocyte membranes in the bone marrow. This promotes megakaryocyte maturation and increases platelet production. Despite a 2-6% incidence of thrombotic events during TPO-RA treatment, it remains uncertain whether TPO-RAs elevate thrombosis rates. A comprehensive search of electronic databases was conducted using the relevant search criteria. To assess the risk of bias, the included studies were assessed using the revised Cochrane Risk of Bias Assessment Tool 2.0, and a meta-analysis was performed using RevMan 5.4.1. A total of 1,698 patients with ITP were included from randomized controlled trials (RCTs). There were 26 thromboembolic events in the TPO-RAs group and 4 in the control group. However, there was no significant difference in the incidence of thrombotic events between the two groups [odds ratio (OR)=1.76, 95% confidence interval (CI): 0.78-4.00, P=0.18], even if the duration of treatment was >12 weeks (OR=2.46, 95% CI: 0.81-7.43, P=0.11). Subgroup analysis showed that none of the four drugs significantly increased the incidence of thrombotic events (romiplostim: OR=0.92, 95% CI: 0.14-6.13, P=0.93; eltrombopag: OR=2.32, 95% CI: 0.64-8.47, P=0.20; avatrombopag: OR=4.15, 95% CI: 0.20-85.23, P=0.36; and hetrombopag: OR=0.76, 95% CI: 0.03-18.76, P=0.87). There was also no significant difference in the results of the double-blinded placebo-controlled RCTs (OR=1.21, 95% CI: 0.41-3.58, P=0.73). Compared to patients with ITP who did not receive TPO-RA treatment, those receiving TPO-RA treatment did not exhibit a significantly increased risk of thrombotic events.
PubMed: 38357229
DOI: 10.3892/br.2024.1732 -
Haematologica Jan 2008Clinical definitions and terminology vary greatly in clinical studies on idiopathic thrombocytopenic purpura (ITP). An objective assessment of this heterogeneity may be... (Review)
Review
Clinical definitions and terminology vary greatly in clinical studies on idiopathic thrombocytopenic purpura (ITP). An objective assessment of this heterogeneity may be of interest, providing a basis for standardizing ITP terminology. A systematic review of the recent literature on ITP in adults was carried out. The following items were extracted from the articles for comparison: platelet count cut-off values to decide treatment and type of response; timing for evaluating the response to treatment; evaluation of bleeding symptoms; criteria to define initial, chronic and refractory forms. A total of 79 papers, among those published or referenced from 2000 to 2006, were considered eligible. No consensus among the different authors was found on several issues, including:platelet count for definition of ITP; grading of severity; definition of chronic ITP; platelet threshold to start treatment; platelet count to define response to treatment and timing for evaluating the response to therapy. There was only major consensus for the length of disease duration required to diagnose chronic ITP, the criteria for splenectomy and the definition of refractory ITP. Confusing terminology and an unacceptable heterogeneity of clinical definitions used for management decisions and to describe outcomes were evident in recent ITP literature. This makes it very difficult to compare different studies and to share data and clinical experiences. A standardization of terminology and definitions used in ITP is urgently needed.
Topics: Adult; Blood Platelets; Chronic Disease; Diagnosis, Differential; Hematology; Humans; Immunoglobulins, Intravenous; Middle Aged; Platelet Count; Prognosis; Purpura, Thrombocytopenic, Idiopathic; Risk; Splenectomy; Terminology as Topic; Treatment Outcome
PubMed: 18166791
DOI: 10.3324/haematol.11582 -
Thrombosis Research Jun 2022With the advent of COVID-19 vaccines, hospitalization rates and progression to severe COVID-19 disease have reduced drastically. Most of the adverse events reported by... (Review)
Review
INTRODUCTION
With the advent of COVID-19 vaccines, hospitalization rates and progression to severe COVID-19 disease have reduced drastically. Most of the adverse events reported by the vaccine recipients were minor. However, autoimmune hematological complications such as vaccine-induced immune thrombotic thrombocytopenia (VITT), immune thrombocytopenic purpura (ITP) and TTP have also been reported post-COVID-19 vaccination. Given this, we sought to reflect on the existing cases of TTP, whether de novo or relapsing, reported after COVID-19 vaccination to further gain insight into any association, if present, and outcomes.
METHODS
We searched PubMed, Embase, and Ebsco databases for published individual case reports on the occurrence or relapse of TTP after receiving any COVID-19 vaccine. A total of 23 articles (27 patients) were included in this qualitative analysis.
RESULTS
The mean age for the patients who developed de novo TTP post-COVID-19 vaccination was 51.3 years. TTP episodes were seen mostly after BNT162b2 vaccine, followed by mRNA-1273 vaccine. All patients with immune TTP except one received plasma exchange (PLEX) and steroids. One patient passed away after two days of hospitalization, likely due to a sudden cardiovascular event.
CONCLUSION
Our review underscores the importance of in-depth anamnesis before vaccination and outlines characteristics of predisposed individuals. Evaluation of post-vaccine thrombocytopenia must include the possibility of TTP given the associated fatality with this condition.
Topics: 2019-nCoV Vaccine mRNA-1273; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Humans; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; Purpura, Thrombotic Thrombocytopenic; SARS-CoV-2; Thrombosis; Vaccination
PubMed: 35533526
DOI: 10.1016/j.thromres.2022.04.020 -
International Journal of Surgery... Sep 2017An accessory spleen (AS) is a lobule of splenic tissue found in ectopic locations. Identification of AS is particularly important in patients with immune... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
An accessory spleen (AS) is a lobule of splenic tissue found in ectopic locations. Identification of AS is particularly important in patients with immune thrombocytopenia (ITP) requiring splenectomy as unrecognized AS can later cause refractory symptoms. The AS can also be a source of significant intraabdominal hemorrhage. The aim of this meta-analysis was to systematically analyze the data on the prevalence, number, location, and morphometry of AS.
MATERIALS AND METHODS
An extensive search of the major electronic databases was conducted to identify all studies that reported relevant data on the AS. No date or language restrictions were applied. Data on the study type, the prevalence of AS, location, morphometry and number of AS per patient were extracted from the eligible studies and pooled into a meta-analysis.
RESULTS
A total of 81 studies (n = 22,487 subjects) were included into the quantitative analysis. The overall pooled prevalence of AS was 14.5% (95%CI: 12.4-16.7), while the pooled prevalence of AS in ITP patients was 16.7% (95%CI: 12.1-21.7). The majority of accessory spleens were located in the splenic hilum (62.1% [95%CI:51.5-76.3]). Moreover, 26% of ITP patients with an AS have more than one.
CONCLUSIONS
The findings of this study provide an evidence-based foundation of anatomical knowledge about the AS. Surgeons should take particular caution in identifying an AS, as unnoticed AS during splenectomy can lead to recurrence of hematological diseases or can be a potential source of bleeding in the future.
Topics: Adult; Choristoma; Female; Humans; Prevalence; Purpura, Thrombocytopenic, Idiopathic; Spleen; Splenectomy
PubMed: 28716661
DOI: 10.1016/j.ijsu.2017.07.045 -
Biology Dec 2020There have been increasing reports of skin manifestations in COVID-19 patients. We conducted a systematic review and included manuscripts describing patients with... (Review)
Review
There have been increasing reports of skin manifestations in COVID-19 patients. We conducted a systematic review and included manuscripts describing patients with positive RT-PCR coronavirus testing from nasopharyngeal swabs who also developed cutaneous manifestations. A total of 655 patients were selected, with different types of skin rashes: Erythematous maculopapular ( = 250), vascular ( = 146), vesicular ( = 99), urticarial ( = 98), erythema multiforme/generalized pustular figurate erythema/Stevens-Johnson syndrome ( = 22), ocular/periocular ( = 14), polymorphic pattern ( = 9), generalized pruritus ( = 8), Kawasaki disease ( = 5), atypical erythema nodosum ( = 3), and atypical Sweet syndrome ( = 1). Chilblain-like lesions were more frequent in the younger population and were linked to a milder disease course, while fixed livedo racemosa and retiform purpura appeared in older patients and seemed to predict a more severe prognosis. For vesicular rashes, PCR determined the presence of herpesviruses in the vesicle fluid, which raised the possibility of herpesvirus co-infections. The erythema-multiforme-like pattern, generalized pustular figurate erythema and Stevens-Johnson syndrome were most frequently linked to hydroxychloroquine intake. A positive PCR determination of SARS-COV-2 from conjunctival swabs suggest that eye discharge can also be contagious. These cutaneous manifestations may aid in identifying otherwise asymptomatic COVID-19 carriers in some cases or predict a more severe evolution in others.
PubMed: 33291502
DOI: 10.3390/biology9120449 -
American Journal of Hematology Nov 2009Splenectomy is a common therapy for adults with chronic idiopathic thrombocytopenic purpura (ITP). Thisstudy was designed to estimate both the short-term surgical... (Meta-Analysis)
Meta-Analysis Review
Splenectomy is a common therapy for adults with chronic idiopathic thrombocytopenic purpura (ITP). Thisstudy was designed to estimate both the short-term surgical non-response rate and the long-term relapse rate after laparoscopic splenectomy. A systematic review was conducted of articles published between January 1, 1991 and January 1, 2008. Selection criteria included: chronic ITP, study enrollment in 1990 or later, > or =12 months of follow-up, > or =15 patients with ITP, > or =75% of patients at least 14 years of age, not HIV positive, not undergoing a second splenectomy, and type of performed splenectomy clearly reported. Data were pooled across studies to estimate rates. We identified 170 articles, of which 23 met our inclusion criteria (all observational studies). These studies represent 1,223 laparoscopic splenectomies (71 or 5.6% were converted to open splenectomy during surgery). The pooled short-term surgical non-response rate among the 18 studies reporting data was 8.2% (95% CI 5.4-11.0). The pooled long-term relapse rate across all 23 studies was 43.6 per 1,000 patient years (95% CI 28.2-67.2). This translates to an approximate failure rate of 28% at 5 years for all patients undergoing splenectomy. Studies with shorter durations of follow-up had significantly higher pooled relapse rates than studies with longer follow-up (P = 0.04). Laparoscopicsplenectomy is effective for most patients. Splenectomy may have higher initial relapse rates, particularly, in the first 2 years after surgery, and the rate may decline over time. Am. J. Hematol. 2009. (c) 2009 Wiley-Liss, Inc.
Topics: Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Humans; Laparoscopy; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; Recurrence; Splenectomy; Time Factors; Treatment Failure; Young Adult
PubMed: 19714591
DOI: 10.1002/ajh.21501 -
BMC Pediatrics Nov 2019We have recognized 15 children with jSLE and the antecedent of IgA vasculitis (HSP). This association is not broadly present in the literature.
BACKGROUND
We have recognized 15 children with jSLE and the antecedent of IgA vasculitis (HSP). This association is not broadly present in the literature.
AIM
To know the age and gender distribution of children with IgA vasculitis (HSP), compare it to our IgA vasculitis (HSP) + jSLE cases, and identify prognostic factors to develop jSLE within our case series, IgA vasculitis (HSP) vs. IgA vasculitis (HSP) + jSLE.
METHODS
A systematic review was carried out to know the age and gender distribution of children with IgA vasculitis (HSP). The information obtained plus data from 110 children with IgA vasculitis (HSP) from the Instituto Nacional de Pediatría were used to compare groups and identify prognostic factors. We performed a case-control study in patients < 18 years, consisting of 15 cases retrospectively identified with IgA vasculitis (HSP) + jSLE, and 110 IgA vasculitis (HSP) control subjects.
RESULTS
The information of 12,819 IgA vasculitis (HSP) subjects from the systematic review and 110 IgA vasculitis (HSP) controls was obtained and compared to our 15 IgA vasculitis (HSP) + jSLE cases. The mean age of IgA vasculitis (HSP) was 7.1-years vs. 10.4-years of IgA vasculitis (HSP) + jSLE at the HSP diagnosis. Female to male ratio of IgA vasculitis (HSP) was 1:1.33 vs. 1:0.25 of IgA vasculitis (HSP) + jSLE. Patients with IgA vasculitis (HSP) + jSLE had lower levels of Hemoglobin (Hb) compared to patients with IgA vasculitis (HSP) 109 g/L vs. 141 g/L. For the development of jSLE, we found older age and lower levels of Hb as prognostic factors with OR [95% CI]: 1.37 [1.06, 1.89] and 5.39 [2.69, 15.25], respectively.
CONCLUSION
IgA vasculitis (HSP) + jSLE patients are older and have lower levels of Hb than patients with IgA vasculitis (HSP). It is necessary to confirm these findings through a prospective study.
Topics: Adolescent; Age Distribution; Case-Control Studies; Child; Child, Preschool; Female; Hemoglobins; Humans; IgA Vasculitis; Lupus Erythematosus, Systemic; Male; Prognosis; Retrospective Studies; Sex Distribution
PubMed: 31771531
DOI: 10.1186/s12887-019-1829-4