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Immunohematology Jun 2024The high number of D variants can lead to the unnecessary use of Rh immune globulin, overuse of D- RBC units, and anti-D allommunization. D variant prevalence varies...
The high number of D variants can lead to the unnecessary use of Rh immune globulin, overuse of D- RBC units, and anti-D allommunization. D variant prevalence varies among ethnic groups, and knowledge of the main variants present in a specific population, their behavior in serologic tests, and their impact on clinical practice is crucial to define the best serologic tests for routine use. The present study aimed to explore the serologic profile of D variants and to determine which variants are most associated with false-negative D typing results and alloimmunization. Donor samples were selected in two study periods. During the first period, D typing was performed on a semi-automated instrument in microplates, and weak D tests were conducted in tube or gel tests. In the second period, D typing was carried out using an automated instrument with microplates, and weak D tests were performed in solid phase. Samples from patients typed as D+ with anti-D were also selected. All samples were characterized by molecular testing. A total of 37 variants were identified. Discrepancies and atypical reactivity without anti-D formation were observed in 83.4 percent of the samples, discrepant D typing results between donations were seen in 12.3 percent, and D+ patients with anti-D comprised 4.3 percent. DAR1.2 was the most prevalent variant. Weak D type 38 was responsible for 75 percent of discrepant samples, followed by weak D type 11, predominantly detected by solid phase. Among the D variants related to alloimmunization, DIVa was the most prevalent, which was not recognized by serologic testing; the same was true for DIIIc. The results highlight the importance of selecting tests for donor screening capable of detecting weak D types 38 and 11, especially in populations where these variants are more prevalent. In pre-transfusion testing, it is crucial that D typing reagents demonstrate weak reactivity with DAR variants; having a serologic strategy to recognize DIVa and DIIIc is also valuable.
Topics: Humans; Rh-Hr Blood-Group System; Blood Donors; False Negative Reactions; Blood Grouping and Crossmatching; Female; Isoantibodies; Rho(D) Immune Globulin; Male
PubMed: 38910444
DOI: 10.2478/immunohematology-2024-007 -
Immunohematology Jun 2024This case report showcases an extraordinary collaboration to support the transfusion needs of a patient with a rare phenotype and long-standing anemia due to...
This case report showcases an extraordinary collaboration to support the transfusion needs of a patient with a rare phenotype and long-standing anemia due to gastrointestinal bleeding. This report describes the Immunohematology Reference Laboratory testing and logistics of rare blood provision over an 11-year period, as well as a summary of the hematologic, gastroenterologic, and surgical interventions. This case illustrates how a strong collaboration among the clinical team, laboratory, blood center, and the rare donor community facilitated successful management of this patient's anemia until the patient could receive life-changing treatment.
Topics: Humans; Blood Transfusion; Male; Anemia; Female; Gastrointestinal Hemorrhage; Blood Banks; Isoantibodies; Middle Aged
PubMed: 38910443
DOI: 10.2478/immunohematology-2024-011 -
Medicine Jun 2024Immune thrombocytopenic purpura (ITP) comprises ~1% to 4% of thrombocytopenia cases during pregnancy. Factors predicting neonatal thrombocytopenia and associated... (Observational Study)
Observational Study
Immune thrombocytopenic purpura (ITP) comprises ~1% to 4% of thrombocytopenia cases during pregnancy. Factors predicting neonatal thrombocytopenia and associated morbidities due to maternal ITP are unclear. The present study aimed to assess the neonatal outcomes of pregnant women with ITP. Fifty-five pregnant women with ITP and their babies, born between January/2013 and April/2021, were retrospectively reviewed. Maternal and neonatal thrombocytopenia cases other than ITP were excluded from the study. Physical examination, blood count, and cranial/abdominal ultrasonography findings of the newborns were recorded. Neonatal thrombocytopenia was defined as a platelet count < 150 × 109/L. Relationship between neonatal thrombocytopenia and maternal factors was investigated. Thrombocytopenia was detected in 17/55 babies (30.9%), and 8/17 (47.1%) had symptoms of bleeding, all but one being mild bleeding. There was a significant correlation between neonatal platelet counts of < 100 × 109/L and maternal splenectomy history. Incidence of moderate and severe thrombocytopenia was higher (statistically insignificant) in neonates of mothers with ITP. No significant correlation was determined between maternal and neonatal platelet counts. There was a weak insignificant correlation between platelet counts of neonates of mothers with or without thrombocytopenia. A significant correlation was found between the presence of splenectomy before delivery in the mother and a platelet count of < 100 × 109/L in the neonate. Moderate and severe thrombocytopenia was higher in neonates of mothers diagnosed with ITP before pregnancy and needed treatment during pregnancy and/or delivery, but the difference was insignificant. Close follow-up of babies born to mothers with ITP after birth is crucial since there is no significant prediction criterion for developing neonatal thrombocytopenia and associated morbidities.
Topics: Humans; Female; Retrospective Studies; Infant, Newborn; Pregnancy; Purpura, Thrombocytopenic, Idiopathic; Cross-Sectional Studies; Adult; Platelet Count; Pregnancy Complications, Hematologic; Thrombocytopenia, Neonatal Alloimmune; Splenectomy
PubMed: 38905433
DOI: 10.1097/MD.0000000000038587 -
Air Medical Journal 2024Recent years have seen increased discussion surrounding the benefits of damage control resuscitation, prehospital transfusion (PHT) of blood products, and the use of... (Review)
Review
Recent years have seen increased discussion surrounding the benefits of damage control resuscitation, prehospital transfusion (PHT) of blood products, and the use of whole blood over component therapy. Concurrent shortages of blood products with the desire to provide PHT during air medical transport have prompted reconsideration of the traditional approach of administering RhD-negative red cell-containing blood products first-line to females of childbearing potential (FCPs). Given that only 7% of the US population has blood type O negative and 38% has O positive, some programs may be limited to offering RhD-positive blood products to FCPs. Adopting the practice of giving RhD-positive blood products first-line to FCPs extends the benefits of PHT to such patients, but this practice does incur the risk of future hemolytic disease of the fetus and newborn (HDFN). Although the risk of future fetal mortality after an RhD-incompatible transfusion is estimated to be low in the setting of acute hemorrhage, the number of FCPs who are affected by this disease will increase as more air medical transport programs adopt this practice. The process of monitoring and managing HDFN can also be time intensive and costly regardless of the rates of fetal mortality. Air medical transport programs planning on performing PHT of RhD-positive red cell-containing products to FCPs should have a basic understanding of the pathophysiology, prevention, and management of hemolytic disease of the newborn before introducing this practice. Programs should additionally ensure there is a reliable process to notify receiving centers of potentially RhD-incompatible PHT because alloimmunization prophylaxis is time sensitive. Facilities receiving patients who have had PHT must be prepared to identify, counsel, and offer alloimmunization prophylaxis to these patients. This review aims to provide air medical transport professionals with an understanding of the pathophysiology and management of HDFN and provide a template for the early management of FCPs who have received an RhD-positive red cell-containing PHT. This review also covers the initial workup and long-term anticipatory guidance that receiving trauma centers must provide to FCPs who have received RhD-positive red cell-containing PHT.
Topics: Humans; Female; Air Ambulances; Rh-Hr Blood-Group System; Pregnancy; Erythrocyte Transfusion; Erythroblastosis, Fetal; Adult
PubMed: 38897700
DOI: 10.1016/j.amj.2024.03.012 -
International Journal of Molecular... May 2024Red blood cell (RBC) transfusion, limited by patient alloimmunization, demands accurate blood group typing. The Rh system requires specific attention due to the...
Red blood cell (RBC) transfusion, limited by patient alloimmunization, demands accurate blood group typing. The Rh system requires specific attention due to the limitations of serological phenotyping methods. Although these have been compensated for by molecular biology solutions, some RhCE ambiguities remain unresolved. The mRNA length is compatible with full-length analysis and haplotype discrimination, but the mRNA analyses reported so far are based on reticulocyte isolation and molecular biology protocols that are fastidious to implement in a routine context. We aim to present the most efficient reticulocyte isolation method, combined with an RT-PCR sequencing protocol that embraces the phasing of all haplotype configurations and identification of any allele. Two protocols were tested for reticulocyte isolation based either on their size/density properties or on their specific antigenicity. We show that the reticulocyte sorting method by antigen specificity from EDTA blood samples collected up to 48 h before processing is the most efficient and that the combination of an -specific RT-PCR followed by allele-specific sequencing enables analysis of cDNA haplotypes. All samples analyzed show full concordance between phenotype and haplotype sequencing. Two samples from the immunohematology laboratory with ambiguous results were successfully analyzed and resolved, one of them displaying a novel allele (*03 c.340C>T).
Topics: Humans; Rh-Hr Blood-Group System; Haplotypes; Alleles; Reticulocytes; RNA, Messenger; Blood Transfusion; Phenotype
PubMed: 38892055
DOI: 10.3390/ijms25115868 -
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 -
Scientific Reports Jun 2024Periodontitis is a chronic inflammatory disease that affects the periodontal tissues. Although it is associated with various systemic diseases, the impact of...
Periodontitis is a chronic inflammatory disease that affects the periodontal tissues. Although it is associated with various systemic diseases, the impact of periodontitis on kidney transplantation (KT) outcomes, particularly allograft rejection, remains unclear. This study investigated the effect of periodontitis on transplant immunity, specifically examining Porphyromonas gingivalis-derived lipopolysaccharide (LPS-PG). In vitro experiments revealed that LPS-PG increased regulatory T cells (Tregs) in Lewis rat spleen cells. In a mixed lymphocyte reaction assay, concentrations of interferon-γ, indicative of alloreactivity, were lower than in controls when LPS-PG was added to the culture and when LPS-PG-administered Lewis rat spleen cells were used as responders. In a rat KT model, LPS-PG administration to recipients promoted mild tubulitis and low serum creatinine and blood urea nitrogen levels 5 days post-KT compared with PBS-administered controls. Furthermore, LPS-PG-administered recipients had an elevated Treg proportion in their peripheral blood and spleen cells, and increased infiltrating Tregs in kidney allografts, compared with controls. The elevated Treg proportion in peripheral blood and spleen cells had a significant negative correlation with serum creatinine, suggesting elevated Tregs modulated allograft rejection. These findings suggest that periodontitis might modulate alloimmune reactivity through LPS-PG and Tregs, offering insights to refine immunosuppressive strategies for KT recipients.
Topics: Animals; Lipopolysaccharides; Porphyromonas gingivalis; Kidney Transplantation; Rats; T-Lymphocytes, Regulatory; Rats, Inbred Lew; Male; Graft Rejection; Allografts; Periodontitis; Disease Models, Animal; Spleen
PubMed: 38886503
DOI: 10.1038/s41598-024-64771-5 -
Journal of Pregnancy 2024There is insufficient evidence to assess the risk of the production of clinically important alloimmune irregular red blood cell (RBC) antibodies in first-time pregnant... (Comparative Study)
Comparative Study
Comparison of the Detection Rate and Specificity of Irregular Red Blood Cell Antibodies Between First-Time Pregnant Women and Women With a History of Multiple Pregnancies Among 18,010 Chinese Women.
There is insufficient evidence to assess the risk of the production of clinically important alloimmune irregular red blood cell (RBC) antibodies in first-time pregnant women. Using the microcolumn gel antiglobulin method, 18,010 Chinese women with a history of pregnancy and pregnant women were screened for irregular RBC antibodies, and for those with positive test results, antibody specificity was determined. The detection rate and specificity of irregular RBC antibodies in women with a history of multiple pregnancies (two or more) and first-time pregnant women were determined. In addition to 25 patients who passively acquired anti-D antibodies via an intravenous anti-D immunoglobulin injection, irregular RBC antibodies were detected in 121 (0.67%) of the 18,010 women. Irregular RBC antibodies were detected in 93 (0.71%) of the 13,027 women with a history of multiple pregnancies, and antibody specificity was distributed mainly in the Rh, MNSs, Lewis, and Kidd blood group systems; irregular RBC antibodies were detected in 28 (0.56%) of the 4983 first-time pregnant women, and the antibody specificity was distributed mainly in the MNSs, Rh, and Lewis blood group systems. The difference in the percentage of patients with irregular RBC antibodies between the two groups was insignificant ( = 1.248, > 0.05). Of the 121 women with irregular RBC antibodies, nine had anti-Mur antibodies, and one had anti-Di antibodies; these antibodies are clinically important but easily missed because the antigenic profile of the reagent RBCs that are commonly used in antibody screens does not include the antigens that are recognized by these antibodies. Irregular RBC antibody detection is clinically important for both pregnant women with a history of multiple pregnancies and first-time pregnant women. Mur and Di should be included in the antigenic profile of reagent RBCs that are used for performing antibody screens in the Chinese population.
Topics: Humans; Female; Pregnancy; Erythrocytes; China; Adult; Pregnancy, Multiple; Isoantibodies; Rho(D) Immune Globulin; Sensitivity and Specificity; Antibody Specificity; MNSs Blood-Group System; Asian People; Kidd Blood-Group System; East Asian People
PubMed: 38883212
DOI: 10.1155/2024/5539776 -
Transplantation Direct Jul 2024Mesangial expansion (ME) is an understudied histologic lesion in renal allografts. The current Banff score is not reproducible and may miss important ME features. The...
BACKGROUND
Mesangial expansion (ME) is an understudied histologic lesion in renal allografts. The current Banff score is not reproducible and may miss important ME features. The study aimed to improve the quantification of ME using morphometry, assess changes over time, and determine its association with allograft loss.
METHODS
We studied ME in 1-y and 5-y surveillance biopsies in 835 kidney transplants performed between January 2000 and December 2013. ME was assessed using the Banff score by a central pathologist and by morphometry. We derived 3 different morphometric measures: (1) %ME (%glomeruli with ME in ≥2 lobules, like Banff ); (2) %ME (%glomeruli with any ME lesion); and (3) %ME area (sum of all ME areas/all glomerular tuft areas). Unadjusted and adjusted Cox models assessed the risk of death-censored allograft loss.
RESULTS
From 1- to 5-y biopsies, the mean Banff score increased from 0.18 to 0.34, whereas %ME increased from 2.5% to 13.3%. Banff score had modest correlations with morphometric ME measures. Moderate-severe %ME was present in 20.1% of 5-y biopsies, whereas only 6.6% of Banff scores were. In general, higher ME on both 1- and 5-y biopsies was associated with a deceased donor, older recipient age, recipient diabetes/obesity (present in >50% of severely affected biopsies), higher hemoglobin A1c at 5 y posttransplant, and recurrent kidney disease. Higher ME on 5-y biopsies was associated with delayed graft function. A higher Banff score at 1-y biopsy and morphometry ME measures at 5-y biopsy were associated with rejection during the first year posttransplant. Morphometric ME measures were associated with allograft loss independent of Banff scores and all clinical characteristics, including kidney function and recurrent disease. The model with %ME had the highest c-statistic (0.872).
CONCLUSIONS
Banff score underestimates the pervasiveness of ME in 5-y biopsies. ME is common and associated with alloimmune and nonalloimmune causes of graft loss.
PubMed: 38881746
DOI: 10.1097/TXD.0000000000001652 -
Food and Chemical Toxicology : An... Jun 2024Human milk lactoferrin (hmLF) is a glycoprotein with well-known effects on immune function. Helaina Inc. has used a glycoengineered yeast, Komatagaella phaffii, to...
Workshop report: A study roadmap to evaluate the safety of recombinant human lactoferrin expressed in Komagataella phaffii intended as an ingredient in conventional foods - Recommendations of a scientific expert panel.
Human milk lactoferrin (hmLF) is a glycoprotein with well-known effects on immune function. Helaina Inc. has used a glycoengineered yeast, Komatagaella phaffii, to produce recombinant human lactoferrin (Helaina rhLF, Effera™) that is structurally similar to hmLF with intended uses as a food ingredient. However, earlier FDA reviews of rhLF were withdrawn due to insufficient safety data and unanswered safety questions the experts and FDA raised about the immunogenicity/immunotoxicity risks of orally ingested rhLF. Helaina organized a panel of leading scientists to build and vet a safety study roadmap containing the studies and safety endpoints needed to address these questions. Panelists participated in a one-day virtual workshop in June 2023 and ensuing discussions through July 2023. Relevant workshop topics included physicochemical properties of LF, regulatory history of bovine LF and rhLF as food ingredients in the FDA's generally recognized as safe (GRAS) program, and synopses of publicly available studies on the immunogenicity/alloimmunization, immunotoxicology, iron homeostasis, and absorption, distribution, metabolism, and excretion of rhLF. Panelists concluded that the safety study roadmap addresses the unanswered safety questions and the intended safe use of rhLF as a food ingredient for adults and agreed on broad applications of the roadmap to assess the safety and support GRAS of other recombinant milk proteins with immunomodulatory functions.
PubMed: 38880466
DOI: 10.1016/j.fct.2024.114817