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British Journal of Haematology May 2019Fetal and neonatal alloimmune thrombocytopenia (FNAIT) may result in severe bleeding, particularly fetal and neonatal intracranial haemorrhage (ICH). As a result, FNAIT...
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) may result in severe bleeding, particularly fetal and neonatal intracranial haemorrhage (ICH). As a result, FNAIT requires prompt identification and treatment; subsequent pregnancies need close surveillance and management. An international panel convened to develop evidence-based recommendations for diagnosis and management of FNAIT. A rigorous approach was used to search, review and develop recommendations from published data for: antenatal management, postnatal management, diagnostic testing and universal screening. To confirm FNAIT, fetal human platelet antigen (HPA) typing, using non-invasive methods if quality-assured, should be performed during pregnancy when the father is unknown, unavailable for testing or heterozygous for the implicated antigen. Women with a previous child with an ICH related to FNAIT should be offered intravenous immunoglobulin (IVIG) infusions during subsequent affected pregnancies as early as 12 weeks gestation. Ideally, HPA-selected platelets should be available at delivery for potentially affected infants and used to increase the neonatal platelet count as needed. If HPA-selected platelets are not immediately available, unselected platelets should be transfused. FNAIT studies that optimize antenatal and postnatal management, develop risk stratification algorithms to guide management and standardize laboratory testing to identify high risk pregnancies are needed.
Topics: Antigens, Human Platelet; Evidence-Based Medicine; Female; Fetal Diseases; Humans; Immunoglobulins, Intravenous; Infant, Newborn; Intracranial Hemorrhages; Pregnancy; Thrombocytopenia, Neonatal Alloimmune
PubMed: 30828796
DOI: 10.1111/bjh.15813 -
Blood Transfusion = Trasfusione Del... Jan 2019Chronic red blood cell transfusion is the first-line treatment for severe forms of thalassaemia. This therapy is, however, hampered by a number of adverse effects,...
BACKGROUND
Chronic red blood cell transfusion is the first-line treatment for severe forms of thalassaemia. This therapy is, however, hampered by a number of adverse effects, including red blood cell alloimmunisation. The aim of this systematic review was to collect the current literature data on erythrocyte alloimmunisation.
MATERIALS AND METHODS
We performed a systematic search of the literature which identified 41 cohort studies involving 9,256 patients.
RESULTS
The prevalence of erythrocyte alloimmunisation was 11.4% (95% CI: 9.3-13.9%) with a higher rate of alloimmunisation against antigens of the Rh (52.4%) and Kell (25.6%) systems. Overall, alloantibodies against antigens belonging to the Rh and Kell systems accounted for 78% of the cases. A higher prevalence of red blood cell alloimmunisation was found in patients with thalassaemia intermedia compared to that among patients with thalassaemia major (15.5 vs 12.8%).
DISCUSSION
Matching transfusion-dependent thalassaemia patients and red blood cell units for Rh and Kell antigens should be able to reduce the risk of red blood cell alloimmunisation by about 80%.
Topics: Erythrocyte Transfusion; Erythrocytes; Humans; Prevalence; Rh Isoimmunization; Rh-Hr Blood-Group System; Thalassemia; Transfusion Reaction
PubMed: 30653458
DOI: 10.2450/2019.0229-18 -
Vox Sanguinis Jan 2019In Caucasians, fetal/neonatal alloimmune thrombocytopenia (FNAIT) is most commonly due to maternal HPA-1a antibodies. HPA-1a typing followed by screening for anti-HPA-1a...
BACKGROUND AND OBJECTIVES
In Caucasians, fetal/neonatal alloimmune thrombocytopenia (FNAIT) is most commonly due to maternal HPA-1a antibodies. HPA-1a typing followed by screening for anti-HPA-1a antibodies in HPA-1bb women may identify first pregnancies at risk. Our goal was to review results from previous published studies to examine whether the maternal antibody level to HPA-1a could be used to identify high-risk pregnancies.
MATERIALS AND METHODS
The studies included were categorized by recruitment strategies: screening of unselected pregnancies or samples analyzed from known or suspected FNAIT patients.
RESULTS
Three prospective studies reported results from screening programmes, and 10 retrospective studies focused on suspected cases of FNAIT. In 8 studies samples for antibody measurement, performed by the monoclonal antibody immobilization of platelet antigen (MAIPA) assay, and samples for determining fetal/neonatal platelet count were collected simultaneously. In these 8 studies, the maternal antibody level correlated with the risk of severe thrombocytopenia. The prospective studies reported high negative predictive values (88-95%), which would allow for the use of maternal anti-HPA-1a antibody level as a predictive tool in a screening setting, in order to identify cases at low risk for FNAIT. However, due to low positive predictive values reported in prospective as well as retrospective studies (54-97%), the maternal antibody level is less suited for the final diagnosis and for guiding antenatal treatment.
CONCLUSION
HPA-1a antibody level has the potential to predict the severity of FNAIT.
Topics: Antigens, Human Platelet; Biomarkers; Female; Humans; Infant, Newborn; Integrin beta3; Maternal Serum Screening Tests; Platelet Count; Pregnancy; Thrombocytopenia, Neonatal Alloimmune
PubMed: 30565711
DOI: 10.1111/vox.12725 -
Transfusion Medicine Reviews Jan 2019Red blood cells (RBC) transfusion is critical in managing acute and chronic complications in sickle cell disease (SCD); however, it is complicated by RBC...
Red blood cells (RBC) transfusion is critical in managing acute and chronic complications in sickle cell disease (SCD); however, it is complicated by RBC alloimmunization, iron overload, transfusion reactions and infection. Several reports documented an increased incidence of alloantibodies in transfused individuals with SCD, especially for Rh and Kell antigens. As a result, the National Institutes of Health Expert Panel and British Society for Haematology guidelines recommend primary matching for C/c, E/e and K antigens in addition to ABO/RhD for RBC transfusions. However, the evidence supporting these recommendations was cited as limited and understanding of alloimmunization in SCD is evolving. To examine the limitations of the evidence, we undertook a systematic review of evidence behind recommendations for limited and extended serologic and genotypic RBC antigen matching to reduce alloimmunization, autoimmunization and transfusion reactions. Searches of PubMed, Embase, Cochrane, and Web of Science databases using MeSH index and free text terms between 1976 through October 2015 and papers and captured through July 2016 through review references in papers, word of mouth, and ongoing Google Scholar and Medline Alerts identified 303 unique articles. Nineteen articles met inclusion criteria and were classified by the Oxford Centre Evidence Based levels of evidence. Strengthening the Reporting of Observational Studies in Epidemiology checklists were completed for 18 of the 19 studies. There were no prospective randomized controlled trials. Sixteen of the articles were cohort studies, two were cross-sectional studies, and one decision tree model examining costs. Low-quality evidence from observational cohort studies supports that alloimmunization prevalence can be decreased by extending serological RBC antigen matching. Transfusion reactions are generally poorly and inconsistently reported. There was no evidence reporting the effect prophylactic genotypic matching has on alloimmunization, autoimmunization or transfusion reactions. There were no studies comparing prophylactic genotypic matching to serologic matching. High-quality evidence was lacking to support clinical decision making regarding best transfusion practices. Multicenter prospective randomized clinical trials are needed to determine best strategies for reducing the rate of alloimmunization using serologic and genotypic matching.
Topics: ABO Blood-Group System; Anemia, Sickle Cell; Blood Group Incompatibility; Blood Grouping and Crossmatching; Blood Transfusion; Cross-Sectional Studies; Erythrocyte Transfusion; Erythrocytes; Genotype; Humans; Isoantibodies; Observational Studies as Topic; Prospective Studies; Rh-Hr Blood-Group System; Transfusion Reaction
PubMed: 30122266
DOI: 10.1016/j.tmrv.2018.07.003 -
The Cochrane Database of Systematic... Aug 2018Globally, sickle cell disease (SCD) is one of the commonest severe monogenic disorders, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Globally, sickle cell disease (SCD) is one of the commonest severe monogenic disorders, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Red blood cell (RBC) transfusions are used to treat complications of SCD, e.g. acute chest syndrome (ACS) (this often involves a single transfusion episode), or they can be part of a regular long-term transfusion programme to prevent SCD complications.
OBJECTIVES
To summarize the evidence in Cochrane Reviews of the effectiveness and safety of RBC transfusions versus no transfusion, or restrictive (to increase the total haemoglobin) versus liberal (to decrease the haemoglobin S level below a specified percentage) transfusion, for treating or preventing complications experienced by people with SCD.
METHODS
We included Cochrane Reviews of randomised or quasi-randomised controlled trials published in the Cochrane Database of Systematic Reviews, that addressed various SCD complications and had RBC transfusion as an intervention or comparator. We assessed the methodological quality of included reviews according to the AMSTAR quality assessment.
MAIN RESULTS
We included 15 Cochrane Reviews, 10 of which had no included studies with an RBC transfusion intervention (five reported RCTs with other interventions; and five contained no studies). Five of the 15 reviews included participants randomised to RBC transfusion, but in one of these reviews only 10 participants were randomised with no usable data. Four reviews (nine trials with 1502 participants) reported data comparing short- or long-term RBC transfusions versus standard care, disease-modifying agents, a restrictive versus a liberal transfusion strategy and long-term RBC transfusions versus transfusions to treat complications. All reviews were of high quality according to AMSTAR quality assessment, however, the quality of the included trials was highly variable across outcomes. Trials were downgraded according to GRADE methodology for risk of bias, indirectness (most trials were conducted in children with HbSS), and imprecision (outcomes had wide confidence intervals).In all four reviews and all comparisons there was little or no difference in the risk of death (very low-quality evidence). There were either no deaths or death was a rare event.Short-term RBC transfusion versus standard care (one review: two trials, 434 participants, GRADE very low- to low-quality evidence)In people undergoing low- to medium-risk surgery, RBC transfusions may decrease the risk of acute chest syndrome (ACS) in people with African haplotypes compared to standard care (low-quality evidence), but there was little or no difference in people with the Arabic haplotype (very-low quality evidence). There was also little or no difference in the risk of other SCD-related or transfusion-related complications (very-low quality evidence).Long-term RBC transfusion versus standard care (two reviews: three trials, 405 participants, very low- to moderate-quality evidence)In children and adolescents at high risk of stroke (abnormal transcranial doppler (TCD) velocities or silent cerebral infarct (SCI)), long-term RBC transfusions probably decrease the risk of stroke (moderate-quality evidence) and may decrease the risk of ACS and painful crisis compared to standard care (low-quality evidence). Long-term RBC transfusions may also decrease the risk of SCI in children with abnormal TCD velocities (low-quality evidence), but there may be little or no difference in the risk of SCI in children with normal TCD velocities and previous SCI (low-quality evidence).In children and adolescents already receiving long-term RBC transfusions for preventing stroke, in comparison to standard care, continuing long-term RBC transfusions may reduce the risk of SCI (low-quality evidence) but we do not know whether there is a difference in the risk of stroke (very-low quality evidence). In children with normal TCD velocities and SCI there was little or no difference in the risk of alloimmunisation or transfusion reactions, but RBC transfusions may increase the risk of iron overload (low-quality evidence).Long-term RBC transfusion versus RBC transfusion to treat complications (one review: one trial, 72 participants, very low- to low-quality evidence)In pregnant women, long-term RBC transfusions may decrease the risk of painful crisis compared to transfusion for complications (low-quality evidence); but there may be little or no difference in the risk of other SCD-related complications or transfusion reactions (very-low quality evidence).RBC transfusion versus disease-modifying agents (hydroxyurea) (two reviews: two trials; 254 participants, very low- to low-quality evidence)For primary prevention of stroke in children, with abnormal TCD and no severe vasculopathy on magnetic resonance imaging/magnetic resonance angiography (MRI/MRA), who have received at least one year of RBC transfusions, we do not know whether there is a difference between RBC transfusion and disease-modifying agents in the risk of stroke; SCI; ACS; or painful crisis (very-low quality evidence). There may be little or no difference in the risk of iron overload (low-quality evidence).Similarly, for secondary prevention of stroke in children and adolescents, we do not know whether there is a difference between these interventions in the risk of stroke; SCI; or ACS (very-low quality evidence); but hydroxyurea with phlebotomy may increase the risk of painful crisis and global SCD serious adverse events compared to RBC transfusion (low-quality evidence). There may be little or no difference in the risk of iron overload (low-quality evidence).Restrictive versus liberal RBC transfusion strategy (one review: one trial; 230 participants, very low-quality evidence)In people undergoing cholecystectomy, there was little or no difference between strategies in the risk of SCD-related or transfusion-related complications (very-low quality evidence).
AUTHORS' CONCLUSIONS
This overview provides support from two high-quality Cochrane Reviews for the use of RBC transfusions in preventing stroke in children and adolescents at high risk of stroke (abnormal TCDs or SCI) and evidence that it may decrease the risk of SCI in children with abnormal TCD velocities. In addition RBC transfusions may reduce the risk of ACS and painful crisis in this population.This overview highlights the lack of high-quality evidence in adults with SCD and the number of reviews that have no evidence for the use of RBC transfusions across a spectrum of SCD complications. Also of concern is the variable and often incomplete reporting of patient-relevant outcomes in the included trials such as SCD-related serious adverse events and quality of life.
Topics: Adolescent; Anemia, Sickle Cell; Antisickling Agents; Child; Erythrocyte Transfusion; Humans; Hydroxyurea; Randomized Controlled Trials as Topic; Stroke; Systematic Reviews as Topic
PubMed: 30067867
DOI: 10.1002/14651858.CD012082.pub2 -
Transfusion Medicine (Oxford, England) Jun 2019Transfusion therapy is a common practice in the treatment of anaemia and can cause erythrocyte alloimmunisation. To systematise data related to erythrocyte...
Transfusion therapy is a common practice in the treatment of anaemia and can cause erythrocyte alloimmunisation. To systematise data related to erythrocyte alloimmunisation in patients with sickle cell disease (SCD), a bibliographic search was carried out in September 2017 to search for studies in four electronic databases. (i) Referring to the original work, (ii) being cohort or case-control, (iii) having been developed with individuals with SCD and (iv) having evaluated the erythrocyte alloimmunisation. Two reviewers identified the articles for inclusion in the study, extracted the predetermined data and carried out the evaluation of the methodological quality of the work. 21 studies were selected; the studies included data on 20 636 individuals (children and adults), were mostly published in the last 10 years, were developed in the United States and had high methodological quality. The occurrence of erythrocyte alloimmunisation ranged from 4·4 to 76%, and there was a higher rate of alloimmunisation against antigens of the Rh system. The risk factors for alloimmunisation were age; gender (female); red blood cell (RBC) units received; presence of ≥1 autoantibodies, TNF-α, interleukin (IL1B), human leukocyte antigens (HLA)-DRB1 gene polymorphisms; first blood transfusion (BT) after 5 years of age, transfusion episodic, multiple or during inflammatory events, acute chest syndrome (ACS) and vase-occlusive crisis (VOC); increased percentage of CD41 T memory cells; and positive direct antiglobulin test. Transfusion policies should be developed to protect the patient and his or her health based on the main factors associated with its incidence.
Topics: Anemia, Sickle Cell; Autoantibodies; Erythrocyte Transfusion; Erythrocytes; Female; Humans; Immunization; Isoantibodies; Male; Risk Factors; Sex Factors
PubMed: 29845661
DOI: 10.1111/tme.12543 -
Transfusion Jun 2018Red blood cell (RBC) transfusions remain essential in the treatment of patients with sickle cell disease (SCD) and β-thalassemia. Alloimmunization, a well-documented... (Review)
Review
BACKGROUND
Red blood cell (RBC) transfusions remain essential in the treatment of patients with sickle cell disease (SCD) and β-thalassemia. Alloimmunization, a well-documented complication of transfusion, increases the risk of delayed hemolytic transfusion reactions, complicates crossmatching and identifying compatible units, and delays provision of transfusions. Guidance is required to optimize the RBC product administered to these patients.
STUDY DESIGN AND METHODS
An international, multidisciplinary team conducted a systematic review and developed, following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, recommendations to assist treating physicians and transfusion specialists in their decision to select RBCs for these patients.
RESULTS
Eighteen studies (17 clinical studies and one cost-effectiveness study) were included in the systematic review. The overall quality of the studies was very low. In total, 3696 patients were included: 1680 with β-thalassemia and 2016 with SCD.
CONCLUSION
The panel recommends that ABO D CcEe K-matched RBCs are selected for individuals with SCD and β-thalassemia, even in the absence of alloantibodies, to reduce the risk of alloimmunization. In patients with SCD and β-thalassemia who have developed clinically significant alloantibodies, selection of RBCs antigen negative to the alloantibody is recommended, if feasible. In these patients, selection of more extended phenotype-matched RBCs will likely reduce the risk of further alloimmunization. However, given the limited availability of extended phenotype-matched units, attention should be given to ensure that a delay in transfusion does not adversely affect patient care.
Topics: Anemia, Sickle Cell; Erythrocyte Transfusion; Hemoglobinopathies; Humans; Isoantibodies; Isoantigens; beta-Thalassemia
PubMed: 29697146
DOI: 10.1111/trf.14611 -
The Journal of Heart and Lung... Jul 2018Clinical guidelines recommend vaccinations for solid-organ transplant recipients. However, concern exists that vaccination may stimulate adverse alloimmune responses. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clinical guidelines recommend vaccinations for solid-organ transplant recipients. However, concern exists that vaccination may stimulate adverse alloimmune responses.
METHODS
We systematically reviewed the published literature regarding this aspect of vaccine safety. Electronic databases were searched for interventional and observational studies assessing de novo donor-specific antibodies (DSA) and rejection episodes after vaccination against infectious pathogens. Graft loss was also assessed. A meta-analysis was conducted for prospective, controlled studies. PRISMA reporting guidelines were followed.
RESULTS
Ninety studies (15,645 vaccinated patients and 42,924 control patients) were included. Twelve studies included control groups. The incidence of de novo DSA (14 studies) was 23 of 1,244 patients (1.85%) at 21 to 94 days. The incidence of rejection (83 studies) was 107 episodes in 5,116 patients (2.1%) at 0.7 to 6 months. Meta-analysis of prospective controlled studies (n = 8) showed no increased rejection risk with vaccination compared with no vaccination (RR 1.12, 95% CI 0.75 to 1.70). This finding was supported by data from 3 registry analyses.
CONCLUSIONS
Although the current evidence lacks high-quality, controlled studies, the currently available data provide reassurance that clinicians should recommend appropriate vaccination for their transplant patients as the risk of de novo DSA and rejection is relatively low.
Topics: Graft Rejection; Humans; Organ Transplantation; Vaccination
PubMed: 29609844
DOI: 10.1016/j.healun.2018.03.001 -
The Cochrane Database of Systematic... Mar 2018Exchange transfusion and phototherapy have traditionally been used to treat jaundice and avoid the associated neurological complications. Because of the risks and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Exchange transfusion and phototherapy have traditionally been used to treat jaundice and avoid the associated neurological complications. Because of the risks and burdens of exchange transfusion, intravenous immunoglobulin (IVIg) has been suggested as an alternative therapy for alloimmune hemolytic disease of the newborn (HDN) to reduce the need for exchange transfusion.
OBJECTIVES
To assess the effect and complications of IVIg in newborn infants with alloimmune HDN on the need for and number of exchange transfusions.
SEARCH METHODS
We performed electronic searches of CENTRAL, PubMed, Embase (Ovid), Web of Science, CINAHL (EBSCOhost), Academic Search Premier, and the trial registers ClinicalTrials.gov and controlled-trials.com in May 2017. We also searched reference lists of included and excluded trials and relevant reviews for further relevant studies.
SELECTION CRITERIA
We considered all randomized and quasi-randomized controlled trials of IVIg in the treatment of alloimmune HDN. Trials must have used predefined criteria for the use of IVIg and exchange transfusion therapy to be included.
DATA COLLECTION AND ANALYSIS
We used the standard methods of Cochrane and its Neonatal Review Group. We assessed studies for inclusion and two review authors independently assessed quality and extracted data. We discussed any differences of opinion to reach consensus. We contacted investigators for additional or missing information. We calculated risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) for categorical outcomes. We calculated mean difference (MD) for continuous variables. We used GRADE criteria to assess the risk of bias for major outcomes and to summarize the level of evidence.
MAIN RESULTS
Nine studies with 658 infants fulfilled the inclusion criteria. Term and preterm infants with Rh or ABO (or both) incompatibility were included. The use of exchange transfusion decreased significantly in the immunoglobulin treated group (typical RR 0.35, 95% CI 0.25 to 0.49; typical RD -0.22, 95% CI -0.27 to -0.16; NNTB 5). The mean number of exchange transfusions per infant was also significantly lower in the immunoglobulin treated group (MD -0.34, 95% CI -0.50 to -0.17). However, sensitivity analysis by risk of bias showed that in the only two studies in which the treatment was masked by use of a placebo and outcome assessment was blinded, the results differed; there was no difference in the need for exchange transfusions (RR 0.98, 95% CI 0.48 to 1.98) or number of exchange transfusions (MD -0.04, 95% CI -0.18 to 0.10). Two studies assessed long-term outcomes and found no cases of kernicterus, deafness or cerebral palsy.
AUTHORS' CONCLUSIONS
Although overall results show a significant reduction in the need for exchange transfusion in infants treated with IVIg, the applicability of the results is limited because of low to very low quality of evidence. Furthermore, the two studies at lowest risk of bias show no benefit of IVIg in reducing the need for and number of exchange transfusions. Based on these results, we have insufficient confidence in the effect estimate for benefit of IVIg to make even a weak recommendation for the use of IVIg for the treatment of alloimmune HDN. Further studies are needed before the use of IVIg for the treatment of alloimmune HDN can be recommended, and should include blinding of the intervention by use of a placebo as well as sufficient sample size to assess the potential for serious adverse effects.
Topics: Anemia, Hemolytic; Anemia, Neonatal; Blood Transfusion; Humans; Immunoglobulins, Intravenous; Infant, Newborn; Jaundice, Neonatal; Randomized Controlled Trials as Topic
PubMed: 29551014
DOI: 10.1002/14651858.CD003313.pub2 -
Transfusion Medicine (Oxford, England) Apr 2019The present study aimed to gain more insight into, and summarise, blood donation determinants among migrants or minorities of Sub-Saharan heritage by systematically...
OBJECTIVES
The present study aimed to gain more insight into, and summarise, blood donation determinants among migrants or minorities of Sub-Saharan heritage by systematically reviewing the current literature.
BACKGROUND
Sub-Saharan Africans are under-represented in the blood donor population in Western high-income countries. This causes a lack of specific blood types for transfusions and prevention of alloimmunisation among Sub-Saharan African patients.
METHODS/MATERIALS
Medline, EMBASE, PsycINFO and BIOSIS were searched for relevant empirical studies that focused on barriers and facilitators of blood donation among Sub-Saharan Africans in Western countries until 22 June 2017. Of the 679 articles screened by title and abstract, 152 were subsequently screened by full text. Paired reviewers independently assessed the studies based on predefined eligibility and quality criteria.
RESULTS
Of the 31 included studies, 24 used quantitative and 7 used qualitative research methods. Target cohorts varied from Black African Americans and refugees from Sub-Sahara Africa to specific Sub-Saharan migrant groups such as Comorians or Ethiopians. Main recurring barriers for Sub-Saharan Africans were haemoglobin deferral, fear of needles and pain, social exclusion, lack of awareness, negative attitudes and accessibility problems. Important recurring facilitators for Sub-Saharan Africans were altruism, free health checks and specific recruitment and awareness-raising campaigns.
CONCLUSION
The findings of this review can be used as a starting point to develop recruitment and retention strategies for Sub-Saharan African persons. Further research is needed to gain more insight in the role of these determinants in specific contexts as socioeconomic features, personal histories and host country regulations may differ per country.
Topics: Africa South of the Sahara; Altruism; Black People; Blood Donors; Developed Countries; Humans; Minority Groups; Transients and Migrants
PubMed: 29493019
DOI: 10.1111/tme.12517