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Transfusion Medicine Reviews Apr 2021Hemolytic disease of fetus and newborn (HDFN) imposes great healthcare burden being associated with maternal alloimmunization against parental-inherited fetal red blood... (Meta-Analysis)
Meta-Analysis Review
Hemolytic disease of fetus and newborn (HDFN) imposes great healthcare burden being associated with maternal alloimmunization against parental-inherited fetal red blood cell antigens causing fetal anemia or death. Noninvasive prenatal analysis (NIPT) provides safe fetal RHD genotyping for early identification of risk pregnancies and proper management guidance. We aimed to conduct systematic review and meta-analysis on NIPT's beneficial application, in conjunction with quantitative maternal alloantibody analysis, for early diagnosis of pregnancies at risk. Search for relevant articles was done in; PubMed/Medline, Scopus, and Ovid (January 2006April 2020), including only English-written articles reporting reference tests and accuracy data. Nineteen eligible studies were critically appraised. NIPT was estimated highly sensitive/specific for fetal RHD genotyping beyond 11-week gestation. Amplifications from ≥2 exons are optimum to increase accuracy. NIPT permits cost-effectiveness, precious resources sparing, and low emotional stress. Knowledge of parental ethnicity is important for correct NIPT result interpretations and quantitative screening. Cut-off titer ≥8-up-to-32 is relevant for anti-D alloantibodies, while, lower titer is for anti-K. Alloimmunization is influenced by maternal RHD status, gravida status, and history of adverse obstetrics. In conclusion, NIPT allows evidence-based provision of routine anti-D immunoprophylaxis and estimates potential fetal risks for guiding further interventions. Future large-scale studies investigating NIPT's non-RHD genotyping within different ethnic groups and in presence of clinically significant alloantibodies are needed.
Topics: Blood Group Antigens; Female; Fetus; Genotype; Humans; Isoantibodies; Pregnancy; Prenatal Diagnosis; Rh-Hr Blood-Group System
PubMed: 33781630
DOI: 10.1016/j.tmrv.2021.02.001 -
Journal of Clinical Medicine Apr 2023Neonatal hemochromatosis (NH) is an uncommon, severe disorder that results in fetal loss or neonatal death due to liver failure. NH is currently regarded as the... (Review)
Review
Neonatal hemochromatosis (NH) is an uncommon, severe disorder that results in fetal loss or neonatal death due to liver failure. NH is currently regarded as the phenotypic expression of gestational alloimmune liver disease (GALD). The diagnosis of NH-GALD is rarely prenatally established. In addition to providing a systematic review of the prenatal features that are identifiable using ultrasound (US) and MRI, we suggest a prenatal diagnosis algorithm for use in suspected NH during the first affected pregnancy. From a total of 586 database entries identified in PubMed, Google Scholar, and ResearchGate, we selected 18 studies published from 1993 to 2021 that reported maternal medical and obstetric history, prenatal ultrasound findings, and postpartum outcomes. We investigated the ultrasound and MRI features of these studies, along with the outcome due to this condition. A total of 74 cases were identified. The main reported prenatal US finding was fetal growth restriction (FGR) (33%), followed by oligohydramnios (13%) and hydrops fetalis (13%), with 13% cases described as uneventful. Other rare prenatal findings were fetal anemia, ascites, and abnormal fetal liver and spleen. Most pregnancies ended with fetal/perinatal death or therapeutic interruption of pregnancy. Favorable evolution with treatment (ensanguine transfusion and intravenous immunoglobulin (IVIG)) was reported for only 7% of fetuses. Using T2-weighted MRI, fetal extrahepatic siderosis confirmed prenatally in two cases and postnatally in 11 cases. IVIG treatment throughout subsequent pregnancies was found to significantly improve fetal prognosis. MRI should be indicated in selected cases of oligohydramnios, fetal hydrops, fetal hepatomegaly, ascites, or unexplained FGR or anemia after ruling out all other more frequently encountered conditions. MRI can be used to detect iron overload in the liver and extrahepatic siderosis.
PubMed: 37048762
DOI: 10.3390/jcm12072679 -
Clinical Therapeutics Feb 2020β-Thalassemia is an inherited blood disorder characterized by reduced or no production of adult hemoglobin. Systematic identification of the burden of β-thalassemia...
PURPOSE
β-Thalassemia is an inherited blood disorder characterized by reduced or no production of adult hemoglobin. Systematic identification of the burden of β-thalassemia with contemporary treatments is lacking in published literature. Thus, a gap exists in understanding the baseline burden on which to assess future treatments. Therefore, a systematic literature review (SLR) was performed to assess management and outcomes in patients with transfusion-dependent β-thalassemia (TDT) who received long-term transfusion regimens.
METHODS
Searches of MEDLINE, EMBASE, and 5 conference websites were conducted to identify clinical-practice studies in Italy, France, Germany, Greece, the United States, and the United Kingdom, published since January 2007. The review found 135 articles meeting the SLR criteria.
FINDINGS
Among patients carrying 2 β-thalassemia mutations, 64%-89% underwent regular transfusions at intervals of between 2 and 4 weeks. Transfusion-associated complications that were reported included iron overload, transfusion reactions, alloimmunization, and infections. Analyses of 42, 25, and 73 studies reporting liver iron concentration (median, 8.5 mg/g of dry weight [dw]; interquartile range [IQR], 4.5-11.0 mg/g dw), cardiac * magnetic resonance imaging (median, 27.4 ms; IQR, 26.0-30.2 ms), and serum ferritin (median, 1465.0 ng/mL; IQR, 1238.2-1797.0 ng/mL), respectively, showed wide ranges in iron levels and a general trend toward improved iron control in recent years. Adverse transfusion reactions and alloimmunization were reported in ~50% and 10%-20% in patients, respectively. Rates of transfusion-transmitted infections were highly variable by study but were lower in more recent cohorts. Complications stemming from iron overload and underlying disease captured in this SLR included cardiac disease, liver disease, and endocrine and musculoskeletal disorders. Approximately 10% of patients were diagnosed with heart failure, with rates ranging from 2.9% to 20.9% across 6 studies. Other significant complications reported with β-thalassemia included pain (25%-69%), psychiatric disorders (25%-30%), and reduced health-related quality of life. Despite substantial improvements in survival, patients with TDT remained at an increased risk for early mortality.
IMPLICATIONS
Consistent with improvements in transfusion practices and iron monitoring and management, outcomes in patients with TDT have improved. However, iron overload and disease-associated complications remain a challenge in this population. This review supports the burden of disease affecting patients with β-thalassemia and provides a baseline health status against which to assess future improvements in care.
Topics: Blood Transfusion; Cost of Illness; Humans; beta-Thalassemia
PubMed: 31882227
DOI: 10.1016/j.clinthera.2019.12.003 -
Hematology, Transfusion and Cell Therapy Feb 2024The clinical manifestation of foetal anaemia caused by maternal Kell alloantibodies differs from that caused by non-Kell alloantibodies. Severe anaemia develops in the... (Review)
Review
The role of measuring peak systolic velocity of the middle cerebral artery blood flow and anti-K1 titre during pregnancy to detect foetuses with severe anaemia, foetal hydrops, and the requirement of intrauterine transfusion: A systematic review and meta-analysis.
The clinical manifestation of foetal anaemia caused by maternal Kell alloantibodies differs from that caused by non-Kell alloantibodies. Severe anaemia develops in the foetus in the early weeks of gestation; therefore, proper management and early intervention are important. A systematic review and meta-analysis was performed to determine whether the anti-K1 titre can determine the sequelae of Kell alloimmunised pregnancies. Prospective and retrospective cohort studies were used to conduct a systematic review following a comprehensive literature search, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Studies were screened based on a defined set of inclusion and exclusion criteria. A total of 5143 potential articles were identified. Ten studies were used in the meta-analysis of pregnancy outcomes for a specific anti-K1 titre cut-off. The meta-analysis identified statistical significance for intrauterine transfusion (ARD: 0.351; 95 % CI: 0.593-0.109; p-value = 0.004), hydrops (ARD: 0.808; 95 % CI: 1.145-0.472; p-value <0.001), intrauterine foetal death (ARD: 0.938; 95 % CI:1.344 to -0.533; p-value <0.001) and intrauterine transfusion for Doppler middle cerebral artery >1.5 MoM (ARD: 0.381; 95 % CI:1.079 to -0.317; p-value = 0.285). It was concluded that there is no correlation between anti-K1 titre and Kell sensitised pregnancy outcomes, but monitoring the anti-K1 titre is important to manage the pregnancy and it helps clinicians determine the need for intrauterine transfusions. Doppler middle cerebral artery peak systolic velocity is strongly correlated with foetal anaemia and is an efficient routine method for determining the need for intrauterine transfusions in pregnancies affected by anti-K1.
PubMed: 38429195
DOI: 10.1016/j.htct.2024.02.002 -
Asian Journal of Transfusion Science 2022Repeated allogeneic blood transfusions in thalassemia major patients stimulate the patient's immune system to generate antibodies against foreign erythrocyte antigens.... (Review)
Review
BACKGROUND
Repeated allogeneic blood transfusions in thalassemia major patients stimulate the patient's immune system to generate antibodies against foreign erythrocyte antigens. This study was carried out to systematically review the findings of available studies about the prevalence of alloantibodies and autoantibodies, as well as the type of causative antigens among transfusion-dependent thalassemia patients in Iran.
METHODS
Electronic search was conducted on Medline, PubMed, Cochrane, EMBASE, ScienceDirect, and Persians databases. All relevant articles published from January 1990 to July 2018 were included. Abstracts of conference booklets which that been published in the last 5 years were also included in the meta-analysis. The search language was restricted to English and Persian. The quality of studies was evaluated according to a checklist developed by authors, and Cochrane Risk of Bias Assessment Tool was used to evaluate the risk of bias.
RESULTS
Twenty-three relevant articles met all the inclusion criteria. The prevalence of alloimmunization was 13%. Our study showed that anti-D (25%) and anti-K (25%) were most prevalent among Iranian β-thalassemia patients. Data analysis shows the autoantibody prevalence to be 1% among 3787 patients. Meta-regression revealed that the prevalence of alloantibodies increases with each year as the average age of the study population increases.
CONCLUSION
The prevalence of red blood cell (RBC) alloantibodies in transfused Iranian β-thalassemia patients was high. Appropriate preventive strategies such as RBC phenotyping for patients before beginning transfusion and using extended RBC donor-recipient matching, specifically for Rh and Kell system, could be implemented to avoid complications in thalassemia patients.
PubMed: 36199396
DOI: 10.4103/ajts.AJTS_39_20 -
Ultrasound in Obstetrics & Gynecology :... Dec 2019To evaluate the performance of fetal middle cerebral artery peak systolic velocity (MCA-PSV) ≥ 1.5 multiples of the median (MoM) for the prediction of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the performance of fetal middle cerebral artery peak systolic velocity (MCA-PSV) ≥ 1.5 multiples of the median (MoM) for the prediction of moderate-severe anemia, in untransfused and transfused fetuses.
METHODS
A systematic search was performed to identify relevant observational studies reported in the period 2008-2018 that evaluated the performance of MCA-PSV, using a threshold of 1.5 MoM for the prediction of fetal anemia. Diagnosis of fetal anemia by blood sampling was the reference standard. A hierarchical summary receiver-operating characteristics (hSROC) curve was constructed using random-effects modeling. Subgroup and meta-regression analyses, according to the number of previous intrauterine transfusions, were performed.
RESULTS
Twelve studies and 696 fetuses were included in the meta-analysis. The area under the hSROC curve (AUC) for moderate-severe anemia was 83%. Pooled sensitivity and specificity (95% CI) were 79% (70-86%) and 73% (62-82%), respectively, and positive and negative likelihood ratios were 2.94 (95% CI, 2.13-4.00) and 0.272 (95% CI, 0.188-0.371). When considering only untransfused fetuses, prediction improved, achieving an AUC of 87%, sensitivity of 86% (95% CI, 75-93%) and specificity of 71% (95% CI, 49-87%). A decline in sensitivity for the prediction of moderate-severe anemia by MCA-PSV ≥1.5 MoM was observed (estimate, -5.5% (95% CI, -10.7 to -0.3%), P = 0.039) as the number of previous transfusions increased.
CONCLUSIONS
MCA-PSV ≥ 1.5 MoM for the prediction of moderate-severe anemia in untransfused fetuses shows moderate accuracy (86% sensitivity and 71% specificity), which declines with increasing number of intrauterine transfusions. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Anemia; Blood Flow Velocity; Blood Transfusion, Intrauterine; Female; Fetal Diseases; Fetus; Gestational Age; Humans; Middle Cerebral Artery; Observational Studies as Topic; Predictive Value of Tests; Pregnancy; Sensitivity and Specificity; Severity of Illness Index; Ultrasonography, Doppler, Color
PubMed: 30932276
DOI: 10.1002/uog.20273 -
Transplantation Reviews (Orlando, Fla.) Dec 2021Abdominal wall closure after intestinal, multivisceral or liver transplantation can be a major challenge. Different surgical techniques have been described to close... (Review)
Review
BACKGROUND
Abdominal wall closure after intestinal, multivisceral or liver transplantation can be a major challenge. Different surgical techniques have been described to close complex abdominal wall defects, but results remain variable. Two promising transplant techniques have been developed using either non-vascularized or vascularized donor rectus fascia. This systematic review aimed to evaluate the feasibility, safety, and effectiveness of the two techniques.
METHODS
A systematic review was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Human studies published between January 2000 and April 2020 were included. Methodological quality appraisal was done using an adapted 10-item standardized checklist.
RESULTS
The search resulted in 9 articles including 74 patients. Both techniques proved to be feasible and had similar results. After non-vascularized rectus fascia allotransplantation, there was a slightly higher rate of surgical site infections in the earlier reports. Overall, there were few complications, no fascial graft related rejections or deaths. The included articles scored low on quality appraisal, mostly due to the small number of cases and scarcely reported outcome parameters.
CONCLUSIONS
This systematic literature review reports two emerging new techniques for complex abdominal wall closure in transplant patients, with promising results. Standardized data collection in a prospective manner could give us more detailed information about short- and long-term outcomes. Preclinical animal studies are necessary for a thorough investigation of the mechanisms of graft integration, the risk of hernia development and the alloimmune response against the graft.
Topics: Abdominal Wall; Fascia; Graft Rejection; Humans; Liver Transplantation; Prospective Studies
PubMed: 34147948
DOI: 10.1016/j.trre.2021.100634 -
Vox Sanguinis May 2022The transfusion of D-negative red blood cells (RBCs) to D-negative patients has been widely adopted to prevent anti-D alloimmunization, especially in women of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
The transfusion of D-negative red blood cells (RBCs) to D-negative patients has been widely adopted to prevent anti-D alloimmunization, especially in women of childbearing age. Still, transfusion of D-positive RBCs to D-negative recipients is occasionally inevitable in practice, and the resulting incidence of anti-D in different D-negative groups of patients has not been well summarized.
MATERIALS AND METHODS
We searched the relevant literature using PubMed, Cochrane Library, and Embase databases from inception date to 30 September 2021. We looked for studies of anti-D occurring in D-negative recipients who received D-positive RBC transfusions. The anti-D incidence was summarized with 95% confidence intervals (CIs). Data with similar characteristics were combined using a random-effects model.
RESULTS
About 42 studies (2226 cases), which found anti-D, the exact volume of D-positive RBC transfused, and the follow-up time for anti-D detection, met the inclusion criteria. The pooled anti-D incidence was 64% (95% CI, range 55%-74%) in volunteers receiving small volumes of D-positive RBCs, 84% (95% CI, 74%-94%) in those receiving whole units, 26% (95% CI, 19%-32%) in mixed patients, 12% (95% CI, 8%-16%) in oncology patients, 27% (95% CI, 13%-40%) in trauma patients, 4% (95% CI, 0%-8%) in immune-compromised transplant patients, and 6% (95% CI, 1%-39%) in those with AIDS.
CONCLUSION
Compared with the high frequency of anti-D in healthy D-negative volunteers given D-positive RBCs, we found a lower rate of anti-D immunization in various D-negative patients and almost none in transplant and AIDS patients.
Topics: Acquired Immunodeficiency Syndrome; Anemia, Hemolytic, Autoimmune; Erythrocyte Transfusion; Erythrocytes; Female; Humans; Incidence; Isoantibodies; Rho(D) Immune Globulin
PubMed: 35014050
DOI: 10.1111/vox.13232 -
Blood Advances Jul 2020The most common, severe cases of fetal and neonatal alloimmune thrombocytopenia among whites are caused by antibodies against human platelet antigen 1a (HPA-1a). The... (Meta-Analysis)
Meta-Analysis
The most common, severe cases of fetal and neonatal alloimmune thrombocytopenia among whites are caused by antibodies against human platelet antigen 1a (HPA-1a). The aims of this systematic review and meta-analysis are to determine the association between maternal HLA-DRB3*01:01 and: (1) HPA-1a-alloimmunization and (2) neonatal outcome in children born of HPA-1a-immunized women. A systematic literature search identified 4 prospective and 8 retrospective studies. Data were combined across studies to estimate pooled odds ratios (ORs) and the associated 95% confidence intervals (CIs). The population represented by the prospective studies was more than 150 000. In the prospective studies, there were 64 severely thrombocytopenic newborns (platelet count <50 × 109/L) of whom 3 had intracranial hemorrhage. The mothers of all 64 children were HLA-DRB3*01:01+. The number of severely thrombocytopenic children born of HPA-1a-alloimmunized women in the retrospective studies was 214; 205 of whom were born of HLA-DRB3*01:01+ women. For HLA-DRB3*01:01- women, the OR (95% CI) for alloimmunization was 0.05 (0.00-0.60), and for severe neonatal thrombocytopenia 0.08 (0.02-0.37). This meta-analysis demonstrates that the risk of alloimmunization and of having a child with severe thrombocytopenia are both very low for HPA-1a- women who are HLA-DRB3*01:01-.
Topics: Child; Female; Fetus; HLA-DRB3 Chains; Humans; Infant, Newborn; Prospective Studies; Retrospective Studies; Thrombocytopenia, Neonatal Alloimmune
PubMed: 32717028
DOI: 10.1182/bloodadvances.2020002137 -
BMJ Sexual & Reproductive Health Jul 2022The aim of this review was to systematically review the outcome of routine anti-D administration among unsensitised rhesus (RhD)-negative individuals who have an... (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of this review was to systematically review the outcome of routine anti-D administration among unsensitised rhesus (RhD)-negative individuals who have an abortion. This review is registered with Prospero.
METHODS
A search for all published and ongoing studies, without restrictions on language or publication status, was performed using the following databases from their inception: EBM Reviews Ovid - Cochrane Central Register of Controlled Trials, MEDLINE Ovid (Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily), Embase.com, Popline and Google Scholar. Study types included: randomised controlled trials, controlled trials, cohort and case-control studies from 1971 onwards. The population included women who undergo an abortion (induced, incomplete, spontaneous or septic abortion), medical or surgical <12 weeks, and isoimmunisation in a subsequent pregnancy. The primary outcomes were: (1) development of a positive Kleihauer-Betke test and (2) development of Rh alloimmunisation in a subsequent pregnancy.
RESULTS
A total of 2652 studies were screened with 105 accessed for full-text review. Two studies have been included with high bias appreciated. Both studies found few women to be sensitised in forming antibodies after an abortion. The limited studies available and heterogeneity prevent the conduction of a meta-analysis.
CONCLUSIONS
Rh immunoglobulin has well-documented safety. However, it is not without risks and costs, is a possible barrier to delivering efficient services, and may have limited availability in some countries. The evidence base and quality of studies are currently limited. There is unclear benefit from the recommendation for Rh testing and immunoglobulin administration in early pregnancy. More research is needed as clinical practice guidelines are varied, based on expert opinions and moving away from testing and administration at time of abortion.
IMPLICATIONS
There is limited evidence surrounding medical benefit of Rh testing and immunoglobulin administration in early pregnancy. Further research is needed to define alloimmunisation and immunoglobulin benefit to update standards of care. Additionally, other factors should be considered in forming clinical policies and guidelines such as costs, feasibility and impact on access to care for patients.
Topics: Abortion, Induced; Abortion, Spontaneous; Cohort Studies; Female; Humans; Pregnancy; Rh Isoimmunization
PubMed: 34819315
DOI: 10.1136/bmjsrh-2021-201225