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Transfusion Medicine Reviews Apr 2016Optimal selection of blood donors is critical for ensuring the safety of blood products. The current selection process is concerned principally with the safety of the... (Meta-Analysis)
Meta-Analysis Review
Optimal selection of blood donors is critical for ensuring the safety of blood products. The current selection process is concerned principally with the safety of the blood donor at the time of donation and of the recipient at the time of transfusion. Recent evidence suggests that the characteristics of the donor may affect short- and long-term transfusion outcomes for the transfused recipient. We conducted a systematic review with the primary objective of assessing the association between blood donor characteristics and red blood cell (RBC) transfusion outcomes. We searched MEDLINE, EMBASE, and Cochrane Central databases and performed manual searches of top transfusion journals for all available prospective and retrospective studies. We described study characteristics, methodological quality, and risk of bias and provided study-level effect estimates and, when appropriate, pooled estimates with 95% confidence intervals using the Mantel-Haenszel or inverse variance approach. The overall quality of the evidence was graded using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. From 6121 citations identified by our literature search, 59 studies met our eligibility criteria (50 observational, 9 interventional). We identified the evaluation of association of 17 donor characteristics on RBC transfusion outcome. The risk of bias and confounding of the included studies was high. The quality of evidence was graded as very low to low for all 17 donor characteristics. Potential associations were observed for donor sex with reduced survival at 90 days and 6 months in male recipients that receive donated blood from females (hazard ratio 2.60 [1.09, 6.20] and hazard ratio 2.40 [1.10, 5.24], respectively; n = 1), Human Leukocyte Antigen - antigen D Related (HLA-DR) selected transfusions (odds ratio [OR] 0.39 [0.15, 0.99] for the risk of transplant alloimmunization, n = 9), presence of antileukocyte antibodies (OR 5.84 [1.66, 20.59] for risk of transfusion-related acute lung injury, n = 4), and donor RBC antigens selection (OR 0.20 [0.08, 0.52] for risk of alloimmunization, n = 4). Based on poor quality evidence, positive antileukocyte antibodies, female donor to male recipients, HLA-DR selected RBC transfusion, or donor RBC antigen selection may affect RBC transfusion outcome. Our findings that donor characteristics may be associated with transfusion outcomes warrant establishing vein-to-vein data infrastructure to allow for large robust evaluations. PROSPERO registration number: CRD42013006726.
Topics: Age Factors; Bias; Blood Donors; Donor Selection; Erythrocyte Transfusion; Evidence-Based Medicine; Female; HLA Antigens; Hospital Mortality; Humans; Isoantibodies; Male; Observational Studies as Topic; Research Design; Sex Factors; Survival Analysis; Treatment Outcome; Viremia
PubMed: 26920039
DOI: 10.1016/j.tmrv.2016.01.002 -
JAMA Apr 2014The association between red blood cell (RBC) transfusion strategies and health care-associated infection is not fully understood. (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
The association between red blood cell (RBC) transfusion strategies and health care-associated infection is not fully understood.
OBJECTIVE
To evaluate whether RBC transfusion thresholds are associated with the risk of infection and whether risk is independent of leukocyte reduction.
DATA SOURCES
MEDLINE, EMBASE, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, Cochrane Database of Sytematic Reviews, ClinicalTrials.gov, International Clinical Trials Registry, and the International Standard Randomized Controlled Trial Number register were searched through January 22, 2014.
STUDY SELECTION
Randomized clinical trials with restrictive vs liberal RBC transfusion strategies.
DATA EXTRACTION AND SYNTHESIS
Twenty-one randomized trials with 8735 patients met eligibility criteria, of which 18 trials (n = 7593 patients) contained sufficient information for meta-analyses. DerSimonian and Laird random-effects models were used to report pooled risk ratios. Absolute risks of infection were calculated using the profile likelihood random-effects method.
MAIN OUTCOMES AND MEASURES
Incidence of health care-associated infection such as pneumonia, mediastinitis, wound infection, and sepsis.
RESULTS
The pooled risk of all serious infections was 11.8% (95% CI, 7.0%-16.7%) in the restrictive group and 16.9% (95% CI, 8.9%-25.4%) in the liberal group. The risk ratio (RR) for the association between transfusion strategies and serious infection was 0.82 (95% CI, 0.72-0.95) with little heterogeneity (I2 = 0%; τ2 <.0001). The number needed to treat (NNT) with restrictive strategies to prevent serious infection was 38 (95% CI, 24-122). The risk of infection remained reduced with a restrictive strategy, even with leukocyte reduction (RR, 0.80 [95% CI, 0.67-0.95]). For trials with a restrictive hemoglobin threshold of <7.0 g/dL, the RR was 0.82 (95% CI, 0.70-0.97) with NNT of 20 (95% CI, 12-133). With stratification by patient type, the RR was 0.70 (95% CI, 0.54-0.91) in patients undergoing orthopedic surgery and 0.51 (95% CI, 0.28-0.95) in patients presenting with sepsis. There were no significant differences in the incidence of infection by RBC threshold for patients with cardiac disease, the critically ill, those with acute upper gastrointestinal bleeding, or for infants with low birth weight.
CONCLUSIONS AND RELEVANCE
Among hospitalized patients, a restrictive RBC transfusion strategy was associated with a reduced risk of health care-associated infection compared with a liberal transfusion strategy. Implementing restrictive strategies may have the potential to lower the incidence of health care-associated infection.
Topics: Cross Infection; Erythrocyte Transfusion; Humans; Mediastinitis; Pneumonia; Randomized Controlled Trials as Topic; Risk; Sepsis; Surgical Wound Infection
PubMed: 24691607
DOI: 10.1001/jama.2014.2726 -
Transfusion Sep 2015Invasive Fusarium infection is relatively refractory to available antifungal agents. Invasive fusariosis (IF) occurs almost exclusively in the setting of profound... (Review)
Review
BACKGROUND
Invasive Fusarium infection is relatively refractory to available antifungal agents. Invasive fusariosis (IF) occurs almost exclusively in the setting of profound neutropenia and/or systemic corticosteroid use. Treatment guidelines for IF are not well established, including the role of granulocyte transfusions (GTs) to counter neutropenia.
STUDY DESIGN AND METHODS
We conducted a systematic review, identifying IF cases where GTs were used as adjunctive therapy to antifungal agents and also report a single-center case series detailing our experience (1996-2012) of all IF cases treated with antifungal agents and GTs. In the systematic review cases, GTs were predominantly collected from nonstimulated donors whereas, in the case series, they were universally derived from dexamethasone- and granulocyte-colony-stimulating factor-stimulated donors.
RESULTS
Twenty-three patients met inclusion criteria for the systematic review and 11 for the case series. Response rates after GTs were 30 and 91% in the review and case series, respectively. Survival to hospital discharge remained low at 30 and 45%, respectively. Ten patients in the systematic review and three in the case series failed to achieve hematopoietic recovery and none of these survived. In the case series, donor-stimulated GTs generated mean "same-day" neutrophil increments of 3.35 × 10(9) ± 1.24 × 10(9) /L and mean overall posttransfusion neutrophil increments of 2.46 × 10(9) ± 0.85 × 10(9) /L. Progressive decrements in neutrophil response to GTs in two cases were attributed to GT-related HLA alloimmunization.
CONCLUSION
In patients with IF, donor-stimulated GTs may contribute to high response rates by effectively bridging periods of neutropenia or marrow suppression. However, their utility in the absence of neutrophil recovery remains questionable.
Topics: Female; Fusariosis; Granulocytes; Humans; Leukocyte Transfusion; Male
PubMed: 25857209
DOI: 10.1111/trf.13099 -
Annals of Palliative Medicine Oct 2021To investigate the prevention of platelet transfusion refractoriness (PTR) by platelet antigen gene matching using literature search and meta-analysis. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To investigate the prevention of platelet transfusion refractoriness (PTR) by platelet antigen gene matching using literature search and meta-analysis.
METHODS
PubMed (2000.1-2021.8), Embase (2000.1-2021.8), Cochrane (2010.1-2021.8), and the Chinese Biomedical Literature Database CBM (2010.1-2021.8) were selected as the search database platform. The keywords (HLA/Human leukocyte antigen), (HPA/Human platelet alloantigens), (genotyping/cross-match), platelet transfusion (PLT), and (CCI/Corrected Count Increment) were used for the joint search. After the literature was screened for inclusion and exclusion criteria, the Cochrane intervention handbook was used for bias risk assessment, and Revman 5.3.5 software was used for analysis to obtain the statistical forest plot and funnel plot.
RESULTS
The preliminary results revealed 255 publications, and seven (297 patients in total) were finally included in the quantitative analysis. A total of five publications reported comparison of the 1 h CCI index of HLA or HPA gene matching and PLT after random selection, and the heterogeneity test showed statistical difference (I2=49%, P=0.10). The combined statistical analysis results were: (MD =8.57, 95% CI: 7.30-9.80, Z=13.30, P<0.00001), and while six publications reported the effective rate index of PLT, and the heterogeneity test showed no statistical difference (I2=43%, P=0.12). The fixed effect mode was used to compare the effective rate of the two intervention methods (OR =4.90, 95% CI: 3.50-6.86, Z=9.23, P<0.00001).
DISCUSSION
HLA or HPA gene matching can improve the increment after PLT and reduce the incidence of ineffective PLT.
Topics: Antigens, Human Platelet; Blood Platelets; HLA Antigens; Humans; Platelet Transfusion; Thrombocytopenia
PubMed: 34763457
DOI: 10.21037/apm-21-2603 -
International Journal of Laboratory... Sep 2022Involvement of the central nervous system (CNS) by acute leukemias (ALs) has important implications for risk stratification and disease outcome. The clinical laboratory... (Review)
Review
BACKGROUND
Involvement of the central nervous system (CNS) by acute leukemias (ALs) has important implications for risk stratification and disease outcome. The clinical laboratory plays an essential role in assessment of cerebrospinal fluid (CSF) specimens from patients with ALs at initial diagnosis, at the end of treatment, and when CNS involvement is clinically suspected. The two challenges for the laboratory are 1) to accurately provide a cell count of the CSF and 2) to successfully distinguish blasts from other cell types. These tasks are classically performed using manual techniques, which suffer from suboptimal turnaround time, imprecision, and inconsistent inter-operator performance. Technological innovations in flow cytometry and hematology analyzer technology have provided useful complements and/or alternatives to conventional manual techniques.
AIMS
We performed a PRISMA-compliant systematic review to address the medical literature regarding the development and current state of the art of CSF blast identification using flow cytometry and laboratory hematology technologies.
MATERIALS AND METHODS
We searched the peer reviewed medical literature using MEDLINE (PubMed interface), Web of Science, and Embase using the keywords "CSF or cerebrospinal" AND "blasts(s)".
RESULTS
108 articles were suitable for inclusion in our systematic review. These articles covered 1) clinical rationale for CSF blast identification; 2) morphology-based CSF blast identification; 3) the role of flow cytometry; 4) use of hematology analyzers for CSF blast identification; and 5) quality issues. /L, which is much lower than the original machine count and platelet transfusion was warranted.
DISCUSSION
1) Clinical laboratory testing plays a central role in risk stratification and clinical management of patients with acute leukemias, most clearly in pediatric ALs; 2) studies focused on other patient populations, including adults and patients with AML are less prevalent in the literature; 3) improvements in instrumentation may provide better performance for the classification of CSF specimens.
CONCLUSION
Current challenges include: 1) more precisely characterizing the natural history of AL involvement of the CNS, 2) improvements in automated cell count technology of low cellularity specimens, 3) defining the role of flow MRD testing of CSF specimens and 4) improved recognition of specimen quality by clinicians and laboratory personnel.
Topics: Adult; Cerebrospinal Fluid; Child; Flow Cytometry; Hematology; Humans; Leukemia; Leukocyte Count; Technology
PubMed: 35785436
DOI: 10.1111/ijlh.13869 -
Revista Paulista de Pediatria : Orgao... May 2019Through a systematic review, this essay aimed at revising the concepts of severe pertussis, updating the epidemiology, pathophysiology, clinical presentation, antibiotic...
OBJECTIVE
Through a systematic review, this essay aimed at revising the concepts of severe pertussis, updating the epidemiology, pathophysiology, clinical presentation, antibiotic therapy and auxiliary therapeutic options for symptomatology and complications.
DATA SOURCES
This review considered publications from the last 30years in the databases US National Library of Medicine (PubMed), Scientific Electronic Library Online (SciELO), Literatura Latino-americana e do Caribe em Ciências da Saúde (LILACS), Cochrane, Google Scholar, as well as protocols of the Ministry of Health and recommendations of the Centers for Disease Control and Prevention, related to childhood pertussis (whooping cough), with emphasis on its severe form. This research was based on keywords derived from the terms "pertussis", "azithromycin", "antitussives", "leukocyte reduction" in Portuguese and English. Duplicate studies and those with unavailable full-text were excluded.
DATA SYNTHESIS
Among 556 records found, 54 were selected for analysis. Pertussis, as a reemerging disease, has affected all age groups, evidencing the transient immunity conferred by infection and vaccination. Severe cases occur in neonates and infants, with secondary viral and bacterial complications and malignant pertussis, a longside hyperleukocytosis, respiratory failure and shock. Macrolides continue to be the chosen antibiotics, while antitussives for coughing remain without efficacy. The prompt treatment in Intensive Care Units improved the prognostic in severe cases, and transfusion was promising among procedures for leukoreduction.
CONCLUSIONS
Approaching severe pertussis in childhood remains a challenge for diagnostic and therapy, as the available therapeutic options are still unsatisfactory. Strategies of prevention are expected to reduce the occurrence of severe cases, while new studies should confirm the role of auxiliary therapies.
Topics: Anti-Bacterial Agents; Child, Preschool; Combined Modality Therapy; Global Health; Humans; Infant; Infant, Newborn; Severity of Illness Index; Whooping Cough
PubMed: 31116241
DOI: 10.1590/1984-0462/;2019;37;3;00006 -
Vox Sanguinis Nov 2022Sickle cell disease (SCD) patients are commonly treated with red blood cell (RBC) transfusion. Pretransfusion tests commonly involve limited serological antibody... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Sickle cell disease (SCD) patients are commonly treated with red blood cell (RBC) transfusion. Pretransfusion tests commonly involve limited serological antibody testing. RBC alloimmunization to RBC antigens is a frequently encountered complication seen in chronically transfused patients. Genetic factors such as the human leukocyte antigen (HLA) are known to influence and regulate immune responses. HLAs are highly polymorphic and play an essential role in regulating immune responses, including RBC alloimmunization. The aim of this study was to conduct a systematic review and meta-analysis to evaluate the association between HLA Class II allelic polymorphisms with the possible risk of developing RBC alloantibodies.
MATERIALS AND METHODS
Four databases were systematically searched for relevant studies between the years 2000 and 2021 following the PRISMA guidelines. Four articles met the eligibility and quality criterion, and three alleles, HLA-DRB1*04, HLA-DRB1*15 and HLA-DQB1*03, that were found to be potentially associated with an increased risk in alloantibody formation were included.
RESULTS
The primary outcome measure was alloimmunization by RBC antigen exposure in multiply transfused SCD patients. The total estimate of alloimmunization of the SCD patients was 2.33 (95% CI, 1.58-3.44), demonstrating susceptibility to RBC alloantibody formation. Heterogeneity between the studies was insignificant, suggesting the differences associated with random sampling errors. The results showed that SCD patients carry an increased risk of producing RBC alloantibodies.
CONCLUSION
A strategy to prevent RBC alloimmunization is genotyping for genetically susceptible SCD patients receiving multiple transfusions. Early identification of genetic variants that can potentially increase the risk of RBC alloimmunization could aid in the screening process and selection of phenotypically matched RBC units.
Topics: Humans; Isoantibodies; Anemia, Sickle Cell; Erythrocytes; Erythrocyte Transfusion; Anemia, Hemolytic, Autoimmune; Immunity
PubMed: 36102140
DOI: 10.1111/vox.13351 -
The Cochrane Database of Systematic... Apr 2016Despite modern antimicrobials and supportive therapy bacterial and fungal infections are still major complications in people with prolonged disease-related or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite modern antimicrobials and supportive therapy bacterial and fungal infections are still major complications in people with prolonged disease-related or treatment-related neutropenia. Transfusions of granulocytes have a long history of usage in clinical practice to support and treat severe infection in high-risk groups of patients with neutropenia or neutrophil dysfunction. However, there is considerable current variability in therapeutic granulocyte transfusion practice, and uncertainty about the beneficial effect of transfusions given as an adjunct to antibiotics on mortality. This is an update of a Cochrane review first published in 2005.
OBJECTIVES
To determine the effectiveness and safety of granulocyte transfusions compared to no granulocyte transfusions as adjuncts to antimicrobials for treating infections in people with neutropenia or disorders of neutrophil function aimed at reducing mortality and other adverse outcomes related to infection.
SEARCH METHODS
We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 2). MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 11 February 2016.
SELECTION CRITERIA
RCTs comparing people with neutropenia or disorders of neutrophil dysfunction receiving granulocyte transfusions to treat infection with a control group receiving no granulocyte transfusions. Neonates are the subject of another Cochrane review and were excluded from this review. There was no restriction by outcomes examined, language or publication status.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by the Cochrane Collaboration.
MAIN RESULTS
We identified 10 trials that met the inclusion criteria with a total of 587 participants. We also identified another ongoing trial. These trials were conducted between 1975 and 2015. None of the studies included people with neutrophil dysfunction. The studies differed in the type of infections they included. Six studies included both children and adults, however data were not reported separately for children and adults. The two newest studies gave granulocyte colony stimulating factor (G-CSF) to donors; both were stopped early due to lack of recruitment. Three studies re-randomised participants and therefore quantitative analysis was unable to be performed.Overall the quality of the evidence was very low to low across different outcomes according to GRADE methodology. This was due to many of the studies being at high risk of bias, and many of the outcomes being imprecise.There may be no difference in all-cause mortality over 30 days between participants receiving therapeutic granulocyte transfusions and those that did not (six studies; 321 participants; RR 0.75, 95% CI 0.54 to 1.04; very low-quality evidence). There were no differences between the granulocyte dose subgroups (< 1 x 10(10) per day versus ≥ 1 x 10(10) per day) (test for subgroup differences P = 0.39). There was a difference in all-cause mortality between the studies based on the age of the study (published before 2000 versus published 2000 or later) (test for subgroup differences P = 0.03). There was no difference in all-cause mortality between participants receiving granulocyte transfusions and those that did not in the newest study (one study; 111 participants; RR 1.10, 95% CI 0.70 to 1.73, low-quality evidence). There may be a reduction in all-cause mortality in participants receiving granulocyte transfusions compared to those that did not in studies published before the year 2000 (five studies; 210 participants; RR 0.53, 95% CI 0.33 to 0.85; low-quality evidence).There may be no difference in clinical reversal of concurrent infection between participants receiving therapeutic granulocyte transfusions and those that did not (five studies; 286 participants; RR 0.98, 95% CI 0.81 to 1.19; low-quality evidence).There is insufficient evidence to determine whether there is a difference in pulmonary serious adverse events (1 study; 24 participants; RR 0.85, 95% CI 0.38 to 1.88; very low-quality evidence).None of the studies reported number of days on therapeutic antibiotics, number of adverse events requiring discontinuation of treatment, or quality of life.Six studies reported their funding sources and all were funded by governments or charities.
AUTHORS' CONCLUSIONS
In people who are neutropenic due to myelosuppressive chemotherapy or a haematopoietic stem cell transplant, there is insufficient evidence to determine whether granulocyte transfusions affect all-cause mortality. To be able to detect a decrease in all-cause mortality from 35% to 30% would require a study containing at least 2748 participants (80% power, 5% significance). There is low-grade evidence that therapeutic granulocyte transfusions may not increase the number of participants with clinical resolution of an infection.
Topics: Adult; Cause of Death; Child; Granulocytes; Humans; Infections; Leukocyte Transfusion; Neutropenia; Randomized Controlled Trials as Topic
PubMed: 27128488
DOI: 10.1002/14651858.CD005339.pub2 -
The Indian Journal of Medical Research Aug 2022Sickle cell disease (SCD) constitutes frequently inherited haemoglobin disorders and poses a significant health burden in India. Hydroxyurea (HU), the most commonly used...
BACKGROUND & OBJECTIVES
Sickle cell disease (SCD) constitutes frequently inherited haemoglobin disorders and poses a significant health burden in India. Hydroxyurea (HU), the most commonly used drug, has shown promising results in the clinical management of SCD. The present systematic review was undertaken to assess the efficacy and toxicity of HU in Indian sickle cell patients.
METHODS
A systematic review of studies on HU therapy was conducted to identify the application of HU and its outcome(s) across India. PubMed, Scopus and Cochrane Library was used as data sources for various studies on the efficacy and toxicity of HU therapy for treatment for SCD in India published between January 2001 and October 2021. Two authors independently extracted the data on study design, patient characteristics and therapeutic outcomes of HU in order to determine the study quality of the present review.
RESULTS
Overall, 14 studies were included for a systematic analysis. Of these 11 were prospective, two cross-sectional and one double-blind randomized controlled trial. Low-dose HU (10 mg/kg/day) was found to reduce the rates of vaso-occlusive crisis and hospitalization as well as decreased the requirement of blood transfusion in SCD patients. The foetal haemoglobin (HbF) level was recorded in 13 (80%) studies all of whom reported an elevation in the HbF levels, with a mean increase in per cent HbF from 15.8 to 21.4 per cent across studies. The common adverse events were reversible, mild-to-moderate cytopenia and anaemia.
INTERPRETATION & CONCLUSIONS
The findings of the present review suggest that there is still insufficient information presently to determine the long-term or major adverse effects on organ damage, fertility as well as pregnancy on the use of HU therapy for SCD. Long-term multi-centric studies are thus required to address these problems.
Topics: Humans; Hydroxyurea; Antisickling Agents; Cross-Sectional Studies; Prospective Studies; Anemia, Sickle Cell; Randomized Controlled Trials as Topic
PubMed: 36629190
DOI: 10.4103/ijmr.ijmr_3447_21 -
Biomedicines Jan 2023Hepatitis B infection is a major public health problem globally leading to chronic liver disease and death, which are influenced by various environmental and host... (Review)
Review
Hepatitis B infection is a major public health problem globally leading to chronic liver disease and death, which are influenced by various environmental and host factors including serum 25-hydroxy-vitamin D levels. There is no comprehensive systematic review reporting the association of serum 25-hydroxy-vitamin D levels and different stages of chronic hepatitis B. This study aimed to analyze the association of 25-hydroxy-vitamin D levels in chronic hepatitis B with various determinants and outcomes. A bibliographic search in PubMed, Google Scholar, and Scopus was conducted using the search terms “Vitamin D”, “cholecalciferol”, “calcitriol”, “Hepatitis B”, and “HBV”, which were published until September 2022. Meta-analysis using the “metafor” package in R was conducted with a random effect model. This analysis included 33 studies with 6360 chronic hepatitis B patients. The pooled estimates of serum 25-hydroxy-vitamin D level among CHB cases was 21.05 ng/mL and was significantly lower compared to healthy controls. (p < 0.005). Reduced serum 25-hydroxy-vitamin D level was significantly associated with the severity of liver fibrosis as well as HBe positivity. This analysis suggests that serum 25-hydroxy-vitamin D levels are associated with disease activity and pathobiology, although the exact nature of the cause−effect relationship cannot be discerned from this study.
PubMed: 36672644
DOI: 10.3390/biomedicines11010135