-
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 -
Hematology, Transfusion and Cell Therapy 2024Foetal anaemia is caused by a severe pregnancy complication, haemolytic disease of the foetus and newborn. Intrauterine transfusions (IUTs) are performed to treat foetal... (Review)
Review
BACKGROUND
Foetal anaemia is caused by a severe pregnancy complication, haemolytic disease of the foetus and newborn. Intrauterine transfusions (IUTs) are performed to treat foetal anaemia in alloimmunised pregnant women. If left untreated hydrops can develop thereby reducing the chance of survival. Survival rates have improved but the procedure is not without complications. Procedure-related complications can be associated with early gestational age, hence delaying IUT could improve outcomes. This review aims to determine the effectiveness and safety of IUTs by examining survival and mortality rates, procedure-related complications with associated foetal mortality and the influence of hydrops.
STUDY DESIGN AND METHOD
A systematic review was conducted by searching keywords in four scientific databases from January 2000 to April 2022. A meta-analysis was performed with the OpenMeta-Analyst software using an arcsine transformed proportion with the binary random-effects model and maximum likelihood method.
RESULTS
Fifteen studies were identified as eligible and used in the meta-analysis. The forest plots all showed statistically significant outcomes with heterogeneity of data. Results indicated a greater foetal survival rate with IUT to treat anaemic foetuses, a low foetal mortality rate, and low risk of procedure-related complications associated with foetal loss but a higher risk of foetal mortality when hydrops is present.
CONCLUSION
The findings of this systematic review and meta-analysis provide evidence that IUT is a safe and effective treatment for foetal anaemia in the absence of hydrops when experienced personnel perform the procedure to minimise the risk of procedure-related complications.
PubMed: 38278670
DOI: 10.1016/j.htct.2023.07.013 -
Mediterranean Journal of Hematology and... 2023In patients with SCD, chronic liver damage is a common manifestation. More than 50% of SCD patients have elevated liver enzymes. Common underlying aetiologies include... (Review)
Review
In patients with SCD, chronic liver damage is a common manifestation. More than 50% of SCD patients have elevated liver enzymes. Common underlying aetiologies include sickle cell hepatic crisis, viral hepatitis, sickle cell intrahepatic cholestasis and hepatic sequestration in the acute setting, and cholelithiasis and iron overload in the chronic setting. Autoimmune hepatitis (AIH) is a rare disease that appears to occur more commonly in the sickle cell disease (SCD) population than in the general population. There are many schools of thought as to why this is the case, including the phosphatidylserine hypothesis, the heme inflammatory hypothesis, the complement generation hypothesis, and the transfusion alloimmunization hypothesis. Due to the natural history of the two illnesses, SCD is almost always diagnosed first in cases of dual pathology. Symptoms such as jaundice, fatigue, and abdominal pain are common in SCD, as are abnormal liver function tests (LFTs). These abnormalities, attributed to the other more frequent liver involvements in SCD, can lead to delays in AIH diagnosis in this population. Corticosteroids, sometimes with other immunosuppressive agents, such as azathioprine, are the cornerstone of acute AIH treatment. However, corticosteroid use in the SCD population has been shown to carry an increased risk of vaso-occlusive crises, providing a treatment dilemma. The following is a review of AIH in the SCD population, where we explore the pathophysiology behind the association between the two disorders, discuss an approach to investigating abnormal LFTs in SCD, and examine treatment options in this population with co-existing diseases.
PubMed: 38028400
DOI: 10.4084/MJHID.2023.060 -
Journal of Medicine and Life Jul 2023The D antigen of the Rh blood group is considered clinically significant due to its ability to cause hemolytic transfusion reactions and hemolytic disease in the fetus... (Meta-Analysis)
Meta-Analysis Review
The D antigen of the Rh blood group is considered clinically significant due to its ability to cause hemolytic transfusion reactions and hemolytic disease in the fetus and newborn. This systematic review discusses the prevalence of RhD variants among pregnant women and the importance of including RhD genotyping for prenatal testing to detect RhD variants and prevent anti-D alloimmunization. A comprehensive literature search was conducted using scientific search engines, including PubMed and MEDLINE databases, with the keywords 'anti-D alloimmunization', 'RhD variant', and 'pregnant women.' The review adhered to the PRISMA guidelines. Meta-analysis was performed using MedCalc version 20. A significance level of p≤0.05 was considered statistically significant for all two-tailed tests. The meta-analysis included four articles that met the inclusion criteria. The total prevalence of RhD positivity (RhD+) was 61% (95% CI:34%-85%). The prevalence ranged from 22% to 82%, indicating a high degree of heterogeneity between studies (I2=98.71%, p<0.0001). The overall prevalence of D variants was 15% (95% CI, 9%-23%) with a prevalence of 0.05% to 100%, showing a high degree of heterogeneity between studies (I2=99.89%, p<0.0001). Anti-D alloimmunization could occur in pregnant women with some types of RhD variants. All four studies focused on molecular testing of samples showing inconsistent or weak results with at least two anti-D antibodies using serological methods.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Pregnant Women; Fetus; Prevalence
PubMed: 37900088
DOI: 10.25122/jml-2023-0004 -
Annals of Surgery Open : Perspectives... Sep 2023We aim to investigate the effects of genetically based HLA matching on patient and graft survival, and acute and chronic rejection after liver transplantation.
OBJECTIVE
We aim to investigate the effects of genetically based HLA matching on patient and graft survival, and acute and chronic rejection after liver transplantation.
BACKGROUND
Liver transplantation is a common treatment for patients with end-stage liver disease. In contrast to most other solid organ transplantations, there is no conclusive evidence supporting human leukocyte antigen (HLA) matching for liver transplantations. With emerging alternatives such as transplantation of bankable (stem) cells, HLA matching becomes feasible, which may decrease the need for immunosuppressive therapy and improve transplantation outcomes.
METHODS
We systematically searched the PubMed, Embase, and Cochrane databases and performed a meta-analysis investigating the effect of genetic HLA matching on liver transplantation outcomes (acute/chronic rejection, graft failure, and mortality).
RESULTS
We included 14 studies with 2682 patients. HLA-C mismatching significantly increased the risk of acute rejection (full mismatching: risk ratio = 1.90, 95% confidence interval = 1.08 to 3.33, = 0.03; partial mismatching: risk ratio = 1.33, 95% confidence interval = 1.07 to 1.66, = 0.01). We did not discern any significant effect of HLA mismatching per locus on acute rejection for HLA-A, -B, -DR, and -DQ, nor on chronic rejection, graft failure, or mortality for HLA-DR, and -DQ.
CONCLUSIONS
We found evidence that genetic HLA-C matching reduces the risk of acute rejection after liver transplantation while matching for other loci does not reduce the risk of acute rejection, chronic rejection, graft failure, or mortality.
PubMed: 37746594
DOI: 10.1097/AS9.0000000000000334 -
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 -
Hemolytic disease of the fetus and newborn: systematic literature review of the antenatal landscape.BMC Pregnancy and Childbirth Jan 2023Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past...
BACKGROUND
Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past decades. Considering improvements in HDFN care, the objectives of this systematic literature review were to assess the prenatal treatment landscape and outcomes of Rh(D)- and K-mediated HDFN in mothers and fetuses, to identify the burden of disease, to identify evidence gaps in the literature, and to provide recommendations for future research.
METHODS
We performed a systematic search on MEDLINE, EMBASE and clinicaltrials.gov. Observational studies, trials, modelling studies, systematic reviews of cohort studies, and case reports and series of women and/or their fetus with HDFN caused by Rhesus (Rh)D or Kell alloimmunization. Extracted data included prevalence; treatment patterns; clinical outcomes; treatment efficacy; and mortality.
RESULTS
We identified 2,541 articles. After excluding 2,482 articles and adding 1 article from screening systematic reviews, 60 articles were selected. Most abstracted data were from case reports and case series. Prevalence was 0.047% and 0.006% for Rh(D)- and K-mediated HDFN, respectively. Most commonly reported antenatal treatment was intrauterine transfusion (IUT; median frequency [interquartile range]: 13.0% [7.2-66.0]). Average gestational age at first IUT ranged between 25 and 27 weeks. weeks. This timing is early and carries risks, which were observed in outcomes associated with IUTs. The rate of hydrops fetalis among pregnancies with Rh(D)-mediated HDFN treated with IUT was 14.8% (range, 0-50%) and 39.2% in K-mediated HDFN. Overall mean ± SD fetal mortality rate that was found to be 19.8%±29.4% across 19 studies. Mean gestational age at birth ranged between 34 and 36 weeks.
CONCLUSION
These findings corroborate the rareness of HDFN and frequently needed intrauterine transfusion with inherent risks, and most births occur at a late preterm gestational age. We identified several evidence gaps providing opportunities for future studies.
Topics: Female; Humans; Pregnancy; Erythroblastosis, Fetal; Hydrops Fetalis; Hemolysis; Blood Transfusion, Intrauterine; Fetus
PubMed: 36611144
DOI: 10.1186/s12884-022-05329-z -
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 -
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 -
Pathogens (Basel, Switzerland) Jun 2022In this systematic review, we evaluate the efficacy and safety of blood components treated with pathogen reduction technologies (PRTs). We searched the Medline, Embase,... (Review)
Review
In this systematic review, we evaluate the efficacy and safety of blood components treated with pathogen reduction technologies (PRTs). We searched the Medline, Embase, Scopus, Ovid, and Cochrane Library to identify RCTs evaluating PRTs. Risk of bias assessment and the Mantel-Haenszel method for data synthesis were used. We included in this review 19 RCTs evaluating 4332 patients (mostly oncohematological patients) receiving blood components treated with three different PRTs. Compared with standard platelets (St-PLTs), the treatment with pathogen-reduced platelets (PR-PLTs) does not increase the occurrence of bleeding events, although a slight increase in the occurrence of severe bleeding events was observed in the overall comparison. No between-groups difference in the occurrence of serious adverse events was observed. PR-PLT recipients had a lower 1 and 24 h CI and CCI. The number of patients with platelet refractoriness and alloimmunization was significantly higher in PR-PLT recipients compared with St-PLT recipients. PR-PLT recipients had a higher number of platelet and RBC transfusions compared with St-PLT recipients, with a shorter transfusion time interval. The quality of evidence for these outcomes was from moderate to high. Blood components treated with PRTs are not implicated in serious adverse events, and PR-PLTs do not have a major effect on the increase in bleeding events. However, treatment with PRTs may require a greater number of transfusions in shorter time intervals and may be implicated in an increase in platelet refractoriness and alloimmunization.
PubMed: 35745493
DOI: 10.3390/pathogens11060639