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The Cochrane Database of Systematic... Mar 2021Atypical haemolytic uraemic syndrome (aHUS) is a rare disorder characterised by thrombocytopenia, microangiopathic haemolytic anaemia, and acute kidney injury. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atypical haemolytic uraemic syndrome (aHUS) is a rare disorder characterised by thrombocytopenia, microangiopathic haemolytic anaemia, and acute kidney injury. The condition is primarily caused by inherited or acquired dysregulation of complement regulatory proteins with ~40% of those affected aged < 18 years. Historically, kidney failure and death were common outcomes, however, improved understanding of the condition has led to discovery of novel therapies.
OBJECTIVES
To evaluate the benefits and harms of interventions for aHUS.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies for randomised controlled studies (RCTs) up to 3 September 2020 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. MEDLINE(OVID) 1946 to 27 July 2020 and EMBASE (OVID) 1974 to 27 July 2020 were searched for non-RCTs.
SELECTION CRITERIA
All randomised and non-randomised clinical trials comparing an intervention with placebo, an intervention with supportive therapy, or two or more interventions for aHUS were included. Given the rare nature of the condition in question, prospective single-arm studies of any intervention for aHUS were also included.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted pre-specified data from eligible studies and evaluated risk of bias using a newly developed tool based on existing Cochrane criteria. As statistical meta-analysis was not appropriate, qualitative analysis of data was then performed.
MAIN RESULTS
We included five single-arm studies, all of which evaluated terminal complement inhibition for the treatment of aHUS. Four studies evaluated the short-acting C5 inhibitor eculizumab and one study evaluated the longer-acting C5 inhibitor ravulizumab. All included studies within the review were of non-randomised, single-arm design. Thus, risk of bias is high, and it is challenging to draw firm conclusions from this low-quality evidence. One hundred patients were included within three primary studies evaluating eculizumab, with further data reported from 37 patients in a secondary study. Fifty-eight patients were included in the ravulizumab study. After 26 weeks of eculizumab therapy there were no deaths and a 70% reduction in the number of patients requiring dialysis. Complete thrombotic microangiopathic (TMA) response was observed in 60% of patients at 26 weeks and 65% at two years. After 26 weeks of ravulizumab therapy four patients had died (7%) and complete TMA response was observed in 54% of patients. Substantial improvements were seen in estimated glomerular filtration rate and health-related quality of life in both eculizumab and ravulizumab studies. Serious adverse events occurred in 42% of patients, and meningococcal infection occurred in two patients, both treated with eculizumab.
AUTHORS' CONCLUSIONS
When compared with historical data, terminal complement inhibition appears to offer favourable outcomes in patients with aHUS, based upon very low-quality evidence drawn from five single-arm studies. It is unlikely that an RCT will be conducted in aHUS and therefore careful consideration of future single-arm data as well as longer term follow-up data will be required to better understand treatment duration, adverse outcomes and risk of disease recurrence associated with terminal complement inhibition.
Topics: Antibodies, Monoclonal, Humanized; Atypical Hemolytic Uremic Syndrome; Bias; Complement Inactivating Agents; Glomerular Filtration Rate; Humans; Non-Randomized Controlled Trials as Topic; Quality of Life; Thrombotic Microangiopathies
PubMed: 33783815
DOI: 10.1002/14651858.CD012862.pub2 -
Expert Review of Hematology Feb 2022Immune thrombocytopenia, also known as immune thrombocytopenic purpura (ITP), has emerged as a significant COVID-19-associated complication. This study analyzes the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Immune thrombocytopenia, also known as immune thrombocytopenic purpura (ITP), has emerged as a significant COVID-19-associated complication. This study analyzes the published literature of case reports and case series regarding COVID-19 infection associated with ITP.
METHODOLOGY
In this systematic review and meta-analysis, a systematic search was conducted through PubMed, Web of Science, and Medline through Clarivate and EBSCO to include the eligible studies. The authors utilized Review Manager 5.4 to conduct quantitative data synthesis for the condition of interest analysis.
RESULTS
A total of 13 eligible case reports and case series with 42 patients were included in this study; 54.8% of them were male. The pooled mean age of all participants was (59.5 ± 19) years with a median age of 63 years. The estimated mean time from diagnosis with COVID-19 to ITP development was 18.1 ± 21 days and the mean time to recovery from ITP was 5.8 ± 4.8 days. The pooled random effect of mean platelet count in the included six studies was 14.52, CI [8.79, 20.25].
CONCLUSION
Our analysis shows that ITP secondary to COVID-19 infection is slightly more prevalent among males (54.8%). Elderly patients were more vulnerable to the disease. Most cases developed ITP within 2-3 weeks after COVID-19 infection and recovered in less than one week from ITP.
Topics: Adult; Aged; COVID-19; Humans; Male; Middle Aged; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
PubMed: 35025706
DOI: 10.1080/17474086.2022.2029699 -
Frontiers in Immunology 2020Transplant-associated thrombotic microangiopathy (TA-TMA) is a dangerous and life-threatening complication in patients undergoing hematopoietic stem cell transplantation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Transplant-associated thrombotic microangiopathy (TA-TMA) is a dangerous and life-threatening complication in patients undergoing hematopoietic stem cell transplantation (HSCT). Eculizumab has been used in the treatment of TA-TMA, and several studies have confirmed the benefit of Eculizumab in patients with TA-TMA. However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Eculizumab for TA-TMA.
MATERIALS AND METHODS
We searched PubMed and Embase for studies on the efficacy and safety of Eculizumab in TA-TMA patients. Efficacy outcomes consisted of overall response rate (ORR), complete response rate (CRR), and survival rate at the last follow-up (SR). Safety outcomes were adverse events (AEs), including infection, sepsis, impaired liver function, infusion reactions, and death.
RESULTS
A total of 116 patients from six studies were subjected to meta-analysis. The pooled estimates of ORR, CRR, and SR for TA-TMA patients were 71% (95% CI: 58-82%), 32% (95% CI: 11-56%), and 52% (95% CI: 40-65%), respectively. Only one patient presented with a severe rash, and infection was the most common AEs. The main causes of death were infection and GvHD.
CONCLUSION
Current evidence suggests that Eculizumab improves SR and ORR in patients with TA-TMA and that Eculizumab is well tolerated. However, the number of studies is limited, and the findings are based mainly on data from observational studies. Higher quality randomized controlled trials and more extensive prospective cohort studies are needed.
Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal, Humanized; Child; Child, Preschool; Complement Inactivating Agents; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Middle Aged; Observational Studies as Topic; Survival Rate; Thrombotic Microangiopathies; Treatment Outcome; Young Adult
PubMed: 33552043
DOI: 10.3389/fimmu.2020.564647 -
Journal of Thrombosis and Thrombolysis May 2022Reports of thrombotic response after receiving COVID-19 Adenoviral-Vector Based Vaccines raise concerns about vaccine-induced thrombotic thrombocytopenia (VITT);... (Review)
Review
Reports of thrombotic response after receiving COVID-19 Adenoviral-Vector Based Vaccines raise concerns about vaccine-induced thrombotic thrombocytopenia (VITT); therefore, we conduct this systematic review to report susceptible demographics outcomes, commonalities, and prognosis of reporting cases. We identified published articles by searching PubMed, SCOPUS, and Web of Science from December 2020 till May 2021, with an updated search in September 2021. All case reports and case series reporting thrombotic response after receiving COVID-19 Adenoviral-Vector Based Vaccines were eligible for including. In addition, two authors independently extracted data and assessed the quality of the included studies. A total of 157 patients with thrombotic events after the ChAdOx1 nCoV-19 vaccine and 16 patients with thrombotic events after Ad26.COV2. S vaccine was included in our study. 72% of the ChAdOx1 nCoV-19 cases were females, while in Ad26.COV2.S subgroup, all reported patients were females. The commonest presentations were deep vein thrombosis 20 (12.7%) and cerebral venous sinus thrombosis 18 (11.5%) in the ChAdOx1 nCoV-19 subgroup while cerebral venous sinus thrombosis 14 (87.5%) and pulmonary embolism 2 (12.5%) in the Ad26.COV2. S subgroup. In this study, we described the certain demographics associated with VITT and the clinical presentations of those cases in the ChAdOx1 nCoV-19 and Ad26.COV2. S vaccines. Young individuals, particularly females, may be more susceptible to VITT, and future studies should seek to confirm this association. In addition, the clinical presentation of VITT commonly includes cerebral thrombi, pulmonary embolism, and deep venous thrombosis, but other presentations are also possible, highlighting the importance of clinical vigilance in recent vaccine recipients.
Topics: Ad26COVS1; COVID-19; COVID-19 Vaccines; ChAdOx1 nCoV-19; Female; Humans; Male; Pulmonary Embolism; SARS-CoV-2; Sinus Thrombosis, Intracranial; Thrombocytopenia; Thrombosis; Vaccines
PubMed: 35157188
DOI: 10.1007/s11239-021-02626-w -
PLoS Neglected Tropical Diseases Aug 2021Coagulation mechanisms are reported to be affected in dengue illness and evidenced by prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT).... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Coagulation mechanisms are reported to be affected in dengue illness and evidenced by prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT). The main aim of this systematic review and meta-analysis is to determine the magnitude of coagulation abnormalities among patients with dengue fever infection.
METHOD
This systematic review and meta-analysis were conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The Joana Brigg's Institute (JBI) critical appraisal checklist was used for quality appraisal. STATA version 11 software was used for meta-analysis. The magnitude of coagulation abnormalities among dengue fever patients was determined by using a random-effects model. Subgroup and sensitivity analysis were performed to investigate the possible source of heterogeneity. Egger weighted regression tests were used to check the presence of publication bias among the included articles.
RESULT
Forty-two studies with a total of 12,221 dengue fever patients were eligible for meta-analysis in this study. Of which 22, 15, and 26 studies were used to determine the magnitude of prolonged APTT, PT, and thrombocytopenia, respectively. The magnitude of prolonged APTT and PT among patients with dengue fever infection were 42.91% (95% CI: 30.95, 54.87) I2 = 99.1% and 16.48% (95% CI: 10.95, 22.01) I2 = 97.0%, respectively. Besides, the magnitude of thrombocytopenia among dengue fever patients was 70.29% (95% CI: 62.69, 77.89) I2 = 99.3%. The magnitude of prolonged APTT in children and adults was 51.21% (95% CI: 24.54, 77.89) and 44.89% (95% CI: 28.32, 61.45), respectively. Similarly, the overall magnitude of prolonged PT in children and adults were 13.40% (95% CI: 6.09, 20.71) and 18.73% (95% CI: 7.49, 29.96), respectively.
CONCLUSION
The result of this study showed that there is a high magnitude of prolonged APTT and PT in dengue fever patients. Therefore, screening and early correction of coagulation abnormalities may be helpful to reduce further complications in those patients.
Topics: Adult; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Child; Dengue; Humans; Partial Thromboplastin Time; Prothrombin Time; Thrombocytopenia
PubMed: 34407078
DOI: 10.1371/journal.pntd.0009666 -
Pediatric Critical Care Medicine : a... Jan 2022To present the recommendations and consensus statements with supporting literature for plasma and platelet transfusions in critically ill neonates and children...
Plasma and Platelet Transfusions Strategies in Neonates and Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass or Neonates and Children Supported by Extracorporeal Membrane Oxygenation: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.
OBJECTIVES
To present the recommendations and consensus statements with supporting literature for plasma and platelet transfusions in critically ill neonates and children undergoing cardiac surgery with cardiopulmonary bypass or supported by extracorporeal membrane oxygenation from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.
DESIGN
Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children.
SETTING
Not applicable.
PATIENTS
Critically ill neonates and children following cardiopulmonary bypass or supported by extracorporeal membrane oxygenation.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
A panel of nine experts developed evidence-based and, when evidence was insufficient, expert-based statements for plasma and platelet transfusions in critically ill neonates and children following cardiopulmonary bypass or supported by extracorporeal membrane oxygenation. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed one good practice statement, two recommendations, and three expert consensus statements.
CONCLUSIONS
Whereas viscoelastic testing and transfusion algorithms may be considered, in general, evidence informing indications for plasma and platelet transfusions in neonatal and pediatric patients undergoing cardiac surgery with cardiopulmonary bypass or those requiring extracorporeal membrane oxygenation support is lacking.
Topics: Anemia; Blood Component Transfusion; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Child; Critical Care; Critical Illness; Erythrocyte Transfusion; Evidence-Based Medicine; Extracorporeal Membrane Oxygenation; Hemorrhage; Humans; Infant, Newborn; Plasma; Platelet Transfusion
PubMed: 34989703
DOI: 10.1097/PCC.0000000000002856 -
Archives of Academic Emergency Medicine 2020Multiple lines of evidence have attested that decreased numbers of platelets may serve as a surrogate marker for poor prognosis in a wide range of infectious diseases.... (Review)
Review
INTRODUCTION
Multiple lines of evidence have attested that decreased numbers of platelets may serve as a surrogate marker for poor prognosis in a wide range of infectious diseases. Thus, to provide a well-conceptualized viewpoint demonstrating the prognostic value of thrombocytopenia in COVID-19, we performed a meta-analysis of pertinent literature.
METHODS
The keywords "platelet" OR "thrombocytopenia" AND "COVID-19" OR "coronavirus 2019" OR "2019-nCoV" OR "SARS-CoV-2" were searched in National Library of Medicine Medline/PubMed and Scopus between December 30, 2019, and May 9, 2020 in English without any restriction. The initial search results were first screened by title and abstract, and then full texts of relevant articles representing information on the platelet count (main outcome) with a clinically validated definition of COVID-19 severity were finally selected. To assess the existence of bias in the included studies, the funnel plot and egger plot along with egger tests were used. Also, the heterogeneity among the included studies was tested using the Chi-square test.
RESULTS
The results of our meta-analysis of 19 studies, totaling 3383 COVID-19 patients with 744 (21.9%) severe cases, revealed that non-severe cases have a significantly higher number of platelets and showed that the probability of the emergence of thrombocytopenia is significantly higher in the severe cases with the pooled mean difference of -21.5 (%95 CI: -31.57, -11.43).
CONCLUSION
Decreased number of platelets more commonly associates with severe COVID-19; however, whether the emergence of thrombocytopenia may result in diseases severity or the severity of the disease may decrease platelets, is open to debate.
PubMed: 33134971
DOI: No ID Found -
International Journal of Infectious... Jun 2022To meta-analyse the clinical manifestations, diagnosis, treatment, and mortality of vaccine-induced immune thrombotic thrombocytopenia (VITT) after adenoviral vector... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To meta-analyse the clinical manifestations, diagnosis, treatment, and mortality of vaccine-induced immune thrombotic thrombocytopenia (VITT) after adenoviral vector vaccination.
METHODS
Eighteen studies of VITT after ChAdOx1 nCoV-19 or Ad26.COV2.S vaccine administration were reviewed from PubMed, Scopus, Embase, and Web of Science. The meta-analysis estimated the summary effects and between-study heterogeneity regarding the incidence, manifestations, sites of thrombosis, diagnostic findings, and clinical outcomes.
RESULTS
The incidence of total venous thrombosis after ChAdOx1 nCoV-19 vaccination was 28 (95% CI 12-52, I=100%) per 100,000 doses administered. Of 664 patients included in the quantitative analysis (10 studies), the mean age of patients with VITT was 45.6 years (95% CI 43.8-47.4, I=57%), with a female predominance (70%). Cerebral venous thrombosis (CVT), deep vein thrombosis (DVT)/pulmonary thromboembolism (PE), and splanchnic vein thrombosis occurred in 54%, 36%, and 19% of patients with VITT, respectively. The pooled incidence rate of CVT after ChAdOx1 nCoV-19 vaccination (23 per 100,000 person-years) was higher than that reported in the pre-pandemic general population (0.9 per 100,000 person-years). Intracranial haemorrhage and extracranial thrombosis accompanied 47% and 33% of all patients with CVT, respectively. The antiplatelet factor 4 antibody positivity rate was 91% (95% CI 88-94, I=0%) and the overall mortality was 32% (95% CI 24-41, I=69%), and no significant difference was observed between heparin- and non-heparin-based anticoagulation treatments (risk ratio 0.84, 95% CI 0.47-1.50, I=0%).
CONCLUSIONS
Patients with VITT after SARS-CoV-2 vaccination most frequently presented with CVT following DVT/PE and splanchnic vein thrombosis, and about one-third of patients had a fatal outcome. This meta-analysis should provide a better understanding of VITT and assist clinicians in identifying VITT early to improve outcomes and optimise management.
Topics: Ad26COVS1; COVID-19; COVID-19 Vaccines; ChAdOx1 nCoV-19; Female; Humans; Male; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; SARS-CoV-2; Thrombocytopenia; Thrombosis; Vaccines; Venous Thrombosis
PubMed: 35339716
DOI: 10.1016/j.ijid.2022.03.034 -
Blood Advances Oct 2020Heparin-induced thrombocytopenia (HIT) is a prothrombotic adverse drug reaction occurring in <0.1% to 7% of patients receiving heparin products depending on the patient... (Meta-Analysis)
Meta-Analysis
Heparin-induced thrombocytopenia (HIT) is a prothrombotic adverse drug reaction occurring in <0.1% to 7% of patients receiving heparin products depending on the patient population and type of heparin. Management of HIT is highly dependent on a sequence of tests for which clinicians may or may not have the results when care decisions need to be made. We conducted systematic reviews of the effects of management strategies in persons with acute HIT, subacute HIT A or B, and remote HIT. We searched Medline, EMBASE, and the Cochrane Database through July 2019 for previously published systematic reviews and primary studies. Two investigators independently screened and extracted data and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. We found primarily noncomparative studies and case series assessing effects of treatments, which led to low to very low certainty evidence. There may be little to no difference in the effects between nonheparin parenteral anticoagulants and direct oral anticoagulants in acute HIT. The benefits of therapeutic-intensity may be greater than prophylactic-intensity anticoagulation. Using inferior vena cava filters or platelet transfusion may result in greater harm than not using these approaches. Evidence for management in special situations, such as for patients undergoing cardiovascular interventions or renal replacement therapy, was also low to very low certainty. Additional research to evaluate nonheparin anticoagulants is urgently needed, and the development of novel treatments that reduce thrombosis without increasing hemorrhage should be a priority.
Topics: Anticoagulants; Hemorrhage; Heparin; Humans; Thrombocytopenia; Thrombosis
PubMed: 33095876
DOI: 10.1182/bloodadvances.2020002963 -
The Journal of Arthroplasty May 2024The aim of this study was to investigate the safety of early surgery in hip fracture patients who took clopidogrel and/or aspirin. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this study was to investigate the safety of early surgery in hip fracture patients who took clopidogrel and/or aspirin.
METHODS
A systematic search was conducted using databases, including PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science, for studies relating to early arthroplasty or internal fixation for femoral neck fractures, intertrochanteric fractures, and subtrochanteric fractures in patients taking clopidogrel and/or aspirin. A total of 20 observational studies involving 3,077 patients were included in this meta-analysis, and analyzed in groups of early surgery versus delayed surgery, and clopidogrel and/or aspirin versus nonantiplatelet agents.
RESULTS
Patients in the clopidogrel and/or aspirin group who underwent early surgery had significantly more intraoperative blood loss than those in the non-antiplatelet group (mean difference = 17.96, 95% confidence interval [CI] [4.37, 31.55], P = .01), and patients in the clopidogrel and/or aspirin group had a lower overall incidence of complications after early surgery than those in the delayed surgery group (odds ratio = 0.26, 95% CI [0.14, 0.29], P < .001) and a shorter length of hospital stay (odds ratio = 0.26, 95% CI [0.14, 0.29], P < .001). There was no significant difference in postoperative mortality and other related indicators.
CONCLUSIONS
Early surgery in hip fracture patients taking clopidogrel and/or aspirin appears to be safe based on the available evidence and needs to be clarified by higher quality studies. However, the increased risk of cardiovascular events associated with discontinuation of clopidogrel or clopidogrel combined with aspirin dual antiplatelet therapy requires attention in the perioperative period.
Topics: Humans; Clopidogrel; Aspirin; Platelet Aggregation Inhibitors; Hip Fractures; Femoral Neck Fractures; Observational Studies as Topic
PubMed: 37972664
DOI: 10.1016/j.arth.2023.11.012