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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 -
The Cochrane Database of Systematic... May 2011Fetomaternal alloimmune thrombocytopenia results from the formation of antibodies by the mother which are directed against a fetal platelet alloantigen inherited from... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fetomaternal alloimmune thrombocytopenia results from the formation of antibodies by the mother which are directed against a fetal platelet alloantigen inherited from the father. The resulting fetal thrombocytopenia (reduced platelet numbers) may cause bleeding, particularly into the brain, before or shortly after birth. Antenatal treatment of fetomaternal alloimmune thrombocytopenia includes the administration of intravenous immunoglobulin (IVIG) and/or corticosteroids to the mother to prevent severe fetal thrombocytopenia. IVIG and corticosteroids both have short-term and possibly long-term side effects. IVIG is also costly and optimal regimens need to be identified.
OBJECTIVES
To determine the optimal antenatal treatment of fetomaternal alloimmune thrombocytopenia to prevent fetal and neonatal haemorrhage and death.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 February 2011) and bibliographies of relevant publications and review articles.
SELECTION CRITERIA
Randomised controlled studies comparing any intervention with no treatment, or comparing any two interventions.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility, trial quality and extracted data.
MAIN RESULTS
We included four trials involving 206 people. One trial involving 39 people compared a corticosteroid (prednisone) versus IVIG alone. In this trial, where analysable data were available, there was no statistically significant differences between the treatment arms for predefined outcomes. Three trials involving 167 people compared IVIG plus a corticosteroid (prednisone in two trials and dexamethasone in one trial) versus IVIG alone. In these trials there was no statistically significant difference in the findings between the treatment arms for predefined outcomes (intracranial haemorrhage; platelet count at birth and preterm birth). Lack of complete data sets and important differences in interventions precluded the pooling of data from these trials.
AUTHORS' CONCLUSIONS
The optimal management of fetomaternal alloimmune thrombocytopenia remains unclear. Lack of complete data sets for two trials and differences in interventions precluded the pooling of data from these trials which may have enabled a more developed analysis of the trial findings. Further trials would be required to determine optimal treatment (the specific medication and its dose and schedule). Such studies should include long-term follow up of all children and mothers.
Topics: Antigens, Human Platelet; Dexamethasone; Female; Fetal Diseases; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Prednisone; Pregnancy; Randomized Controlled Trials as Topic; Thrombocytopenia; Thrombocytopenia, Neonatal Alloimmune
PubMed: 21563140
DOI: 10.1002/14651858.CD004226.pub3 -
Transfusion Clinique Et Biologique :... May 2023The development of red blood cell alloimmunization intensifies transfusion complication in thalassaemia patients. The purpose of this paper is to evaluate the existing... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The development of red blood cell alloimmunization intensifies transfusion complication in thalassaemia patients. The purpose of this paper is to evaluate the existing evidence on the prevalence of erythrocyte alloimmunization in China by meta-analysis. We systematically searched cross-sectional studies regarding the alloimmunization of thalassaemia patients with regular blood transfusion in China from year 2000 to May 2021 in the Cochrane library, PubMed, EMBASE, Web of Science, and Chinese databases including CNKI, Wanfang Data, Vip and CBM. Data extraction and quality evaluation of the included studies were performed. Meta-analysis was performed using the DerSimonian and Laird random-effects models with inverse variance weighting. The presence of publication bias was tested by Egger's test, and the methodological quality of each included article was evaluated by the criteria specific to prevalence studies.
RESULTS
A total of 1874 patients and 263 alloantibodies from 11 studies were identified and included in the meta-analysis. The proportion of alloantibodies against antigens belonging to the Rh, MNSs and Kidd systems were as high as 70.3%, 17.9%, and 6.5%, respectively. Meta-analysis showed that the overall prevalence of alloimmunization among transfusion-dependent thalassaemia patients in China is 11.4% (95%CI: 7.2%∼16.3%).
CONCLUSIONS
The characteristics of red blood cell alloimmunization among thalassaemia patients with regular transfusion in China differ greatly from those in other countries. Therefore, transfusion strategies shall be actively adapted in line with thalassaemia patients in China to minimize the risk of alloimmunization.
Topics: Humans; Isoantibodies; Cross-Sectional Studies; Erythrocyte Transfusion; Erythrocytes; Thalassemia; Blood Transfusion; Anemia, Hemolytic, Autoimmune; China
PubMed: 36764573
DOI: 10.1016/j.tracli.2023.02.001 -
Journal of Plastic, Reconstructive &... Feb 2022Acute rejection remains a vexing problem in vascularized composite allotransplantation (VCA). Available immunosuppressive regimens are successful at minimizing... (Review)
Review
BACKGROUND
Acute rejection remains a vexing problem in vascularized composite allotransplantation (VCA). Available immunosuppressive regimens are successful at minimizing alloimmune response and allowing VCA in humans. However, repeated rejection episodes are common, and systemic side effects of the current standard regimen (Tacrolimus, MMF, Prednisone) are dose limiting. Novel immunomodulatory approaches to improve allograft acceptance and minimize systemic toxicity are continuously explored in preclinical models. We aimed to systematically summarize past and current approaches to help guide future research in this complex field.
METHODS
We conducted a systematic review of manuscripts listed in the MEDLINE and PubMed databases. For inclusion, articles had to primarily investigate the effect of a therapeutic approach on prolonging the survival of a skin-containing preclinical VCA model. Non-VCA studies, human trials, anatomical and feasibility studies, and articles written in a language other than English were excluded. We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines.
RESULTS
The search retrieved 980 articles of which 112 articles were ultimately included. The majority of investigations used a rat model. An orthotopic hind limb VCA model was used in 53% of the studies. Cell and drug-based approaches were investigated 58 and 52 times, respectively. We provide a comprehensive review of immunomodulatory strategies used in VCA preclinical research over a timeframe of 44 years.
CONCLUSION
We identify a transition from anatomically non-specific to anatomical models mimicking clinical needs. As limb transplants have been most frequently performed, preclinical research focused on using the hind limb model. We also identify a transition from drug-based suppression therapies to cell-based immunomodulation strategies.
Topics: Animals; Graft Rejection; Humans; Immunomodulation; Immunosuppressive Agents; Rats; Skin; Tacrolimus; Vascularized Composite Allotransplantation
PubMed: 34895853
DOI: 10.1016/j.bjps.2021.11.003 -
Transfusion Medicine Reviews Oct 2012Large scale red blood cell (RBC) antigen genotyping of donors is currently well developed. There is scarce information, however, to select patients who might benefit... (Review)
Review
Large scale red blood cell (RBC) antigen genotyping of donors is currently well developed. There is scarce information, however, to select patients who might benefit from preemptive extended RBC antigen-matched transfusions. Female sex has been proposed as a risk factor for RBC alloimmunization after transfusion. To asses whether females respond differently to RBC alloantigens compared with males, we conducted a literature review on RBC alloimmunization. Clinical studies on RBC alloimmunization incidence were searched for in databases from 1950 through 2011. Studies were included when data were available to calculate the female-to-male risk ratio for alloimmunization. Based on the reported age, adult patients (>18 years) were distinguished from pediatric patients (≤18 years), and articles were analyzed according to disease categories. Thirty articles fulfilled the inclusion criteria. The Mantel-Haenszel risk ratio estimate of combined adult studies showed that women with sickle cell disease had an increased relative risk (27%) on RBC alloantibodies compared with men. Other groups showed equal alloimmunization risk in women and men. Women slightly more often than men possess RBC antibodies. This is likely explained by more exposure to immunizing events through pregnancy and/or transfusions in females with sickle cell disease. The results support the current policy implemented in many countries for Rhesus/Kell matching in patients with a hemoglobinopathy irrespective of sex. Thus, based solely on sex difference, the results do not justify recommending additional matching for women, besides preemptive K and c antigen matching for women during the (pre-) fertile age, as already applied in many European countries for the prevention of fetal morbidity.
Topics: Adolescent; Adult; Aged; Blood Transfusion; Child; Erythrocyte Transfusion; Erythrocytes; Female; Genotype; Humans; Incidence; Isoantibodies; Male; Middle Aged; Pregnancy; Risk; Sex Factors; Transfusion Reaction
PubMed: 22244869
DOI: 10.1016/j.tmrv.2011.12.001 -
Vox Sanguinis Jun 2024Haemolytic disease of the foetus and newborn (HDFN) occurs when maternal antibodies, often triggered by foetal antigens, destroy foetal and neonatal red blood cells.... (Review)
Review
Does high body mass index (>25 kg/m) or weight (>80 kg) reduce the effectiveness of anti-D prophylaxis in Rh(D)-negative pregnant women? A systematic review and meta-analysis.
BACKGROUND AND OBJECTIVES
Haemolytic disease of the foetus and newborn (HDFN) occurs when maternal antibodies, often triggered by foetal antigens, destroy foetal and neonatal red blood cells. Factors like antibody strength, quantity and gestational age influence HDFN severity. Routine antenatal anti-D prophylaxis (RAADP) has significantly reduced HDFN cases. However, the effect of overweight/obesity (body mass index [BMI] > 25/30 kg/m) on anti-D prophylaxis efficacy remains unclear. This systematic review will examine the impact of BMI on anti D prophylaxis effectiveness in Rh(D) negative pregnant women.
MATERIALS AND METHODS
We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. We searched databases from 1996 to 2023, focusing on studies exploring the link between high BMI/weight and anti-D serum levels in Rh(D)-negative pregnant women with Rh(D)-positive foetuses. Ten eligible studies were included, three suitable for meta-analysis. Study quality was assessed using the Strengthening the Reporting Observation Studies in Epidemiology (STROBE) checklist. Statistical analyses included Pearson correlation coefficients and risk differences.
RESULTS
Our meta-analysis revealed a significant negative correlation (r = -0.59, 95% confidence interval [CI]: -0.83 to -0.35, p = 0.007) between high BMI/weight and serial anti-D levels in in Rh(D)-negative pregnant women with Rh(D)-positive foetuses. High BMI/weight had lower odds of serial anti-D level exceeding 30 ng/mL (arcsine risk difference [ARD] = 0.376, 95% CI: 0.143-0.610, p = 0.002). Heterogeneity among studies was low (I = 0).
CONCLUSION
While our analysis suggests a potential linkage between high BMI/weight and reduced efficacy of anti-D prophylaxis, caution is warranted due to study limitations. Variability in study design and confounding factors necessitate careful interpretation. Further research is needed to confirm these findings and refine clinical recommendations.
PubMed: 38889996
DOI: 10.1111/vox.13693 -
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 -
Journal of Perinatology : Official... Jul 2019To estimate the prevalence and characteristics of fetal thrombocytopenia at the time of percutaneous umbilical cord sampling (PUBS) in pregnancies complicated by... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate the prevalence and characteristics of fetal thrombocytopenia at the time of percutaneous umbilical cord sampling (PUBS) in pregnancies complicated by alloimmunization and to conduct a systematic review on fetal thrombocytopenia in these pregnancies.
STUDY DESIGN
Retrospective cohort study of all patients undergoing PUBS at our institution from 2000-2017. Clinical data, including fetal platelet counts, were abstracted from the medical record and analyzed with routine statistical procedures. A systematic review and meta-analysis were also conducted according to standard procedures.
RESULT
At first procedure, prior to any transfusion, 13/36 fetuses (36%) had thrombocytopenia: 11/36 (31%) had moderate thrombocytopenia and 2/36 (6%) had severe thrombocytopenia (14 patients had no platelet count at first procedure). The systematic review identified six studies, and the prevalence of fetal thrombocytopenia at the time of PUBS for alloimmunization was 18% (95% confidence interval 11%, 26%).
CONCLUSION
Thrombocytopenia is common and underappreciated in fetuses undergoing PUBS for alloimmunization.
Topics: Anemia; Antigens, Human Platelet; Blood Group Incompatibility; Female; Fetal Blood; Fetal Diseases; Fetoscopy; Gestational Age; Humans; Platelet Count; Pregnancy; Pregnancy Complications, Hematologic; Retrospective Studies; Thrombocytopenia
PubMed: 31073147
DOI: 10.1038/s41372-019-0388-8 -
Transfusion May 2024Anti-D can be formed after D-incompatible platelet transfusions due to contaminating D+ red blood cells. These antibodies are of particular importance in women of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anti-D can be formed after D-incompatible platelet transfusions due to contaminating D+ red blood cells. These antibodies are of particular importance in women of childbearing potential, because anti-D is most often involved in severe cases of hemolytic disease of the fetus and newborn. This systematic review determined the frequency of anti-D after D+ platelet transfusions and risk factors for D alloimmunization.
STUDY DESIGN AND METHODS
Relevant literature was searched using PubMed, Embase and Web of Science until December 2022. Overall anti-D frequency and risk factors were estimated using a random effects meta-analysis.
RESULTS
In 22 studies, a total of 3028 D- patients received a mean of six D+ platelet transfusions. After a mean follow-up of seven months 106 of 2808 eligible patients formed anti-D. The pooled anti-D frequency was 3.3% (95% CI 2.0-5.0%; I 71%). After including only patients with an undoubtable follow-up of at least 4 weeks, 29 of 1497 patients formed anti-D with a pooled primary anti-D rate of 1.9% (95% CI 0.9-3.2%, I 44%). Women and patients receiving whole blood derived platelets had two and five times higher anti-D rates compared with men and patients receiving apheresis derived platelets, respectively.
DISCUSSION
Anti-D immunization is low after D incompatible platelet transfusions and dependent on recipients' sex and platelet source. We propose anti-D prophylaxis in girls and women, capable of becoming pregnant in the future, that received D+ platelets, regardless of platelet source, to reduce the risk of anti-D induced hemolytic disease of the fetus and newborn.
Topics: Humans; Platelet Transfusion; Rho(D) Immune Globulin; Female; Isoantibodies; Rh-Hr Blood-Group System; Risk Factors; Pregnancy; Blood Group Incompatibility
PubMed: 38634345
DOI: 10.1111/trf.17833 -
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