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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 -
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 -
The Cochrane Database of Systematic... Jan 2013Antibodies to the red cell Rhesus D (RhD) antigen can be produced during pregnancy in a RhD-negative mother carrying a RhD-positive fetus, in particular following... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antibodies to the red cell Rhesus D (RhD) antigen can be produced during pregnancy in a RhD-negative mother carrying a RhD-positive fetus, in particular following feto-maternal haemorrhage at birth or following any procedure that may cause feto-maternal haemorrhage. While the first baby is usually not harmed, these antibodies may cause haemolytic disease of the fetus/newborn (HDFN) in subsequent RhD-positive babies. RhD incompatibility is a major cause of HDFN.To reduce the risk of HDFN, anti-D is given to RhD-negative mothers at 28 or 30 weeks of pregnancy and within 72 hours of potential maternal exposure to fetal red cells. Anit-D is currently available in both intramuscular (IM) and intravenous (IV) preparations.
OBJECTIVES
To compare the efficacy and effectiveness of IM versus IV anti-D IgG in preventing RhD alloimmunization in RhD-negative pregnant women.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2012).
SELECTION CRITERIA
Randomized controlled trials, quasi-randomized trials and cluster-randomized trials comparing IM and IV anti-D for preventing RhD alloimmunization in RhD-negative pregnant women.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and assessed trial quality. Two review authors extracted data. Data were checked for consistency by both authors.
MAIN RESULTS
Two studies involving 447 (with sample sizes 14 and 432) RhD negative women were included. The studies compared IM and IV administration of anti-D prophylaxis. In both studies the women received a 1500 IU (300 microgram) dose of Rhophylac during week 28 of gestation. There was no incidence of RhD alloimmunization in either of the studies, as the sample size was insufficient for meaningful comparison of this uncommon outcome. One of the studies found that the mean anti-D IgG concentrations after IV and IM administration differed up to seven days (36.1 (2.6) ng/mL IV; 19.8 (8.7) ng/mL IM on day seven). However, from two to three weeks post-administration, the concentrations were similar for both routes of administration. None of the women involved in the studies developed antibodies against the RhD antigen.
AUTHORS' CONCLUSIONS
It appears that IM and IV administration of anti-D are equally effective. The number of included studies and the number of participants are not enough to assess whether there are any differences. Anti-D can be administered by IM or IV injection. The choice of IM or IV route of administration will depend on the available preparations, the dose to be administered and also on the patients' preferences. This review found insufficient information upon which to guide practice due to the limited number of included studies, small sample sizes and methodological limitations.
Topics: Administration, Intravenous; Female; Humans; Immunologic Factors; Injections, Intramuscular; Isoantibodies; Pregnancy; Randomized Controlled Trials as Topic; Rh Isoimmunization; Rho(D) Immune Globulin
PubMed: 23440818
DOI: 10.1002/14651858.CD007885.pub2 -
Haemophilia : the Official Journal of... Jul 2010Bernard Soulier syndrome (BSS) is a rare disorder of platelets, inherited mainly as an autosomal recessive trait. It is characterised by qualitative and quantitative... (Review)
Review
Bernard Soulier syndrome (BSS) is a rare disorder of platelets, inherited mainly as an autosomal recessive trait. It is characterised by qualitative and quantitative defects of the platelet membrane glycoprotein (GP) Ib-IX-V complex. The main clinical characteristics are thrombocytopenia, prolonged bleeding time and the presence of giant platelets. Data on the clinical course and outcome of pregnancy in women with Bernard Soulier syndrome is scattered in individual case reports. In this paper, we performed a systematic review of literature and identified 16 relevant articles; all case reports that included 30 pregnancies among 18 women. Primary postpartum haemorrhage was reported in 10 (33%) and secondary in 12 (40%) of pregnancies, requiring blood transfusion in 15 pregnancies. Two women had an emergency obstetric hysterectomy. Alloimmune thrombocytopenia was reported in 6 neonates, with one intrauterine death and one neonatal death. Bernard Soulier syndrome in pregnancy is associated with a high risk of serious bleeding for the mother and the neonate. A multidisciplinary team approach and individualised management plan for such women are required to minimise these risks. An international registry is recommended to obtain further knowledge in managing women with this rare disorder.
Topics: Adult; Bernard-Soulier Syndrome; Blood Transfusion; Female; Humans; Hysterectomy; Infant, Newborn; Platelet Count; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Thrombocytopenia, Neonatal Alloimmune; Young Adult
PubMed: 20070385
DOI: 10.1111/j.1365-2516.2009.02137.x -
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 -
The Cochrane Database of Systematic... Jan 2005Fetomaternal alloimmune thrombocytopenia occurs when the mother produces antibodies against a platelet alloantigen that the fetus has inherited from the father. A... (Review)
Review
BACKGROUND
Fetomaternal alloimmune thrombocytopenia occurs when the mother produces antibodies against a platelet alloantigen that the fetus has inherited from the father. A consequence of this can be a reduced number of platelets (thrombocytopenia) in the fetus, which can result in bleeding whilst in the womb or shortly after birth. In severe cases this bleeding may lead to long-lasting disability or death. Antenatal management of fetomaternal alloimmune thrombocytopenia centres on preventing severe thrombocytopenia in the fetus. Available management options include administration of intravenous immunoglobulins or corticosteroids to the mother or intrauterine transfusion of antigen compatible platelets to the fetus. All options are costly and need to be assessed in terms of potential risk and benefit to both the mother and an individual fetus.
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 trials register (February 2004), EMBASE (1980 to February 2004) and bibliographies of relevant publications and review articles.
SELECTION CRITERIA
Randomised controlled studies comparing any intervention, including corticosteroids with no treatment, or comparing any two interventions.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed eligibility, trial quality and extracted data.
MAIN RESULTS
One study met the inclusion criteria (54 pregnant women). This trial compared intravenous immunoglobulins plus corticosteroid (dexamethasone) with intravenous immunoglobulins alone. No significant differences were reported between the treatment and control groups, in any outcome measured: mean platelet count at birth (weighted mean difference (WMD) 14.10 x 10 9/l, 95% confidence interval (CI) -30.26 to 58.46), mean gestational age at birth (WMD -0.50 weeks, 95% CI -2.69 to 1.69), mean rise in platelet count from first to second fetal blood screen (WMD -3.50 x 10 9/l, 95% CI -24.62 to 17.62) and mean rise in platelet count from birth to first fetal blood screen (WMD 24.40 x 10 9/l (95% CI -14.17 to 62.97)). This trial had adequate methodological quality; however the method used to calculate sample size was inappropriate: therefore the power calculation was not sufficient to determine any significance in differences between the treatment groups.
AUTHORS' CONCLUSIONS
There are insufficient data from randomised controlled trials to determine the optimal antenatal management of fetomaternal alloimmune thrombocytopenia. Future trials should consider the dose of intravenous immunoglobulins, the timing of initial treatment, monitoring of response to treatment by fetal blood sampling, laboratory measures to define pregnancies with a high risk of intercranial haemorrhage, management of non-responders and long-term follow up of children.
Topics: Antigens, Human Platelet; Blood Transfusion, Intrauterine; Dexamethasone; Female; Fetal Diseases; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Platelet Transfusion; Pregnancy; Thrombocytopenia
PubMed: 15674934
DOI: 10.1002/14651858.CD004226.pub2 -
Influence of , , and genetic polymorphisms on disorders in transplant patients: a systematic review.Drug Metabolism and Personalized Therapy Dec 2021The glutathione-S-transferase (GST) enzymes are phase II isoenzymes responsible for protection against free radicals and xenobiotics. Since these proteins are described...
The glutathione-S-transferase (GST) enzymes are phase II isoenzymes responsible for protection against free radicals and xenobiotics. Since these proteins are described as polymorphic, polymorphisms in genes that encode them may alter enzymatic function and contribute to oxidative stress. In this context, such polymorphisms were already associated with several diseases and multiple therapeutic outcomes. A systematic review was performed to evaluate studies regarding the association between polymorphisms in three genes encoding enzymes of the GST family - , , and - and disorders in transplant patients. A total of 125 articles on which inclusion and exclusion criteria were applied were identified at PubMed database. Thirty-two studies met the target criteria and were included in the review. The mechanisms by which genotypes influence the development of disorders in transplant patients differ by disorder: they may participate in it by decreasing metabolism of drugs administered to patients undergoing transplantation, then exposing them to greater toxicity; by decreasing the repair ability against oxidative stress; or by encoding proteins that may be recognized as foreign, setting of an alloimmune reaction. Although some results are better established - such as null genotype's role in the development of toxicity events in transplant patients - others require further evidences, as influence on the development of pulmonary decline and posttransplant diabetes mellitus (PTDM). The importance of investigating these associations lies in a personalized medicine, in which the high-risk genotype patient has its treatment individualized and its care for prophylaxis and surveillance increased, potentially reducing this population's morbimortality.
Topics: Case-Control Studies; Genetic Predisposition to Disease; Genotype; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Polymorphism, Genetic; Risk Factors
PubMed: 34856092
DOI: 10.1515/dmpt-2021-0165 -
American Journal of Reproductive... Oct 2022The efficacy of lymphocyte immunotherapy (LIT) in the treatment of recurrent pregnancy loss (RPL) from alloimmunity has been debated for years. There is conflicting... (Meta-Analysis)
Meta-Analysis
PROBLEM
The efficacy of lymphocyte immunotherapy (LIT) in the treatment of recurrent pregnancy loss (RPL) from alloimmunity has been debated for years. There is conflicting evidence on the therapeutic role of LIT, since the etiology of most cases of RPL is previously classified as idiopathic.
METHOD OF STUDY
A systematic search of PubMed and Cochrane databases was done for randomized controlled trials that assessed the efficacy of paternal lymphocyte or third donor LIT among patients with primary or secondary RPL. The primary outcome was live birth rate after LIT. Random-effect meta-analysis was conducted using the software RevMan 5.4. Pre-planned subgroup analyses of source of lymphocytes, timing and frequency of administration, and concentration per immunization dose were conducted.
RESULTS
Data from eight trials showed a statistically significant benefit of LIT (RR = 1.45, 95% CI 1.05-2.01). The overall live birth rate is higher in the treatment group (65.6%) compared to placebo or no treatment (45.2%). Subgroup analysis based on source of lymphocytes revealed a trend towards benefit with paternal LIT but with wide confidence interval (RR = 1.34, 95% CI = .84-2.14). Multiple doses of immunotherapy before pregnancy and low dose (5×10 cells) LIT showed significant benefit. Sensitivity analysis involving studies with a low risk of bias demonstrated significant benefit of increased live birth rate among patients treated with LIT compared to those who received placebo or no treatment (RR = 1.97, 95% CI = 1.53-2.53).
CONCLUSION
LIT demonstrate benefit in improving pregnancy outcome of patients with RPL from alloimmunity.
Topics: Abortion, Habitual; Birth Rate; Female; Humans; Immunotherapy; Lymphocytes; Pregnancy; Pregnancy Outcome
PubMed: 35894648
DOI: 10.1111/aji.13605 -
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 -
The Cochrane Database of Systematic... 2000The development of Rh immunisation and its prophylactic use since the 1970s has meant that severe Rhesus D (RhD) alloimmunisation is now rarely seen. (Review)
Review
BACKGROUND
The development of Rh immunisation and its prophylactic use since the 1970s has meant that severe Rhesus D (RhD) alloimmunisation is now rarely seen.
OBJECTIVES
The objective of this systematic review was to assess the effects of giving anti-D to Rhesus negative women, with no anti-D antibodies, who had given birth to a Rhesus positive infant.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register, MEDLINE (from 1966 to January 1999) and reference lists of relevant articles. Date of last search of Cochrane Controlled Trials Register: January 1999.
SELECTION CRITERIA
Randomised trials in Rhesus negative women without antibodies who were given anti-D immunoglobulin postpartum compared with no treatment or placebo.
DATA COLLECTION AND ANALYSIS
Assessments of inclusion criteria, trial quality and data extraction were done by each author independently. Initial analyses included all trials. Other analyses assessed the effect of trial quality, ABO compatibility and dose.
MAIN RESULTS
Six eligible trials compared postpartum anti-D prophylaxis with no treatment or placebo. The trials involved over 10,000 women, but trial quality varied. Anti-D lowered the incidence of RhD alloimmunisation six months after birth (relative risk 0.04, 95% confidence interval 0.02 to 0.06), and in a subsequent pregnancy (relative risk 0.12, 95% confidence interval 0. 07 to 0.23). These benefits were seen regardless of the ABO status of the mother and baby and when anti-D was given within 72 hours of birth. Higher doses (up to 200 micro grams) were more effective than lower doses (up to 50 micro grams) in preventing RhD alloimmunisation in a subsequent pregnancy.
REVIEWER'S CONCLUSIONS
Anti-D, given within 72 hours after childbirth, reduces the risk of RhD alloimmunisation in Rhesus negative women who have given birth to a Rhesus positive infant. However the evidence on the optimal dose is limited.
Topics: Female; Humans; Postpartum Period; Rh Isoimmunization; Rho(D) Immune Globulin
PubMed: 10796089
DOI: 10.1002/14651858.CD000021