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Frontiers in Immunology 2024
Topics: Histocompatibility; Transplantation Immunology
PubMed: 38558808
DOI: 10.3389/fimmu.2024.1393026 -
Blood Feb 2024Fifty years ago, people with sickle cell disease (SCD) were discouraged from becoming pregnant, but now, most should be supported if they choose to pursue a pregnancy....
Fifty years ago, people with sickle cell disease (SCD) were discouraged from becoming pregnant, but now, most should be supported if they choose to pursue a pregnancy. They and their providers, however, should be aware of the physiological changes of pregnancy that aggravate SCD and pregnancy's unique maternal and fetal challenges. Maternal problems can arise from chronic underlying organ dysfunction such as renal disease or pulmonary hypertension; from acute complications of SCD such as acute anemia, vaso-occlusive crises, and acute chest syndrome; and/or from pregnancy-related complications such as preeclampsia, sepsis, severe anemia, thromboembolism, and the need for cesarean delivery. Fetal problems include alloimmunization, opioid exposure, fetal growth restriction, preterm delivery, and stillbirth. Before and during pregnancy, in addition to the assessment and care that every pregnant patient should receive, patients with SCD should be evaluated and treated by a multidisciplinary team with respect to their unique maternal and fetal issues.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Anemia, Sickle Cell; Acute Chest Syndrome; Pregnancy Complications; Prenatal Care; Pre-Eclampsia
PubMed: 37979134
DOI: 10.1182/blood.2023020728 -
Transfusion Mar 2024Red cell alloimmunization remains a challenge for individuals with sickle cell disease (SCD) and contributes to increased risk of hemolytic transfusion reactions and...
BACKGROUND
Red cell alloimmunization remains a challenge for individuals with sickle cell disease (SCD) and contributes to increased risk of hemolytic transfusion reactions and associated comorbidities. Despite prophylactic serological matching for ABO, Rh, and K, red cell alloimmunization persists, in part, due to a high frequency of variant RH alleles in patients with SCD and Black blood donors.
STUDY DESIGN AND METHODS
We compared RH genotypes and rates of alloimmunization in 342 pediatric and young adult patients with SCD on chronic transfusion therapy exposed to >90,000 red cell units at five sites across the USA. Genotyping was performed with RHD and RHCE BeadChip arrays and targeted assays.
RESULTS
Prevalence of overall and Rh-specific alloimmunization varied among institutions, ranging from 5% to 41% (p = .0035) and 5%-33% (p = .0002), respectively. RH genotyping demonstrated that 33% RHD and 57% RHCE alleles were variant in this cohort. Patients with RHCE alleles encoding partial e antigens had higher rates of anti-e identified than those encoding at least one conventional e antigen (p = .0007). There was no difference in anti-D, anti-C, or anti-E formation among patients with predicted partial or altered antigen expression compared to those with conventional antigens, suggesting that variant Rh on donor cells may also stimulate alloimmunization to these antigens.
DISCUSSION
These results highlight variability in alloimmunization rates and suggest that a molecular approach to Rh antigen matching may be necessary for optimal prevention of alloimmunization given the high prevalence of variant RH alleles among both patients and Black donors.
Topics: Young Adult; Humans; Child; Erythrocyte Transfusion; Erythrocytes; Anemia, Sickle Cell; Blood Group Antigens; Genotype; Anemia, Hemolytic, Autoimmune; Isoantibodies; Rh-Hr Blood-Group System
PubMed: 38289184
DOI: 10.1111/trf.17740 -
Alternative Therapies in Health and... Sep 2023Neonatal alloimmune thrombocytopenia (NAIT) is an immune disorder characterized by maternal antibodies that destroy fetal platelets, leading to thrombocytopenia. The... (Review)
Review
BACKGROUND
Neonatal alloimmune thrombocytopenia (NAIT) is an immune disorder characterized by maternal antibodies that destroy fetal platelets, leading to thrombocytopenia. The prevalence of NAIT is approximately 0.05% to 0.15%. Fetal and neonatal severe thrombocytopenia represents the most common form of the disease, primarily occurring in firstborn children. It poses a greater risk and harm to the fetus and newborn. Neonatal intracranial hemorrhage is a severe complication of NAIT, resulting in irreversible damage to cranial nerves and potential neonatal death.
OBJECTIVE
This study aims to assess the current advancements in the pathogenesis, clinical characteristics, laboratory evaluation, and therapeutic interventions for neonatal alloimmune thrombocytopenia.
METHODS
This narrative review explores neonatal alloimmune thrombocytopenia through a thorough literature review. The study encompasses the pathogenesis, clinical features, laboratory examination, and treatment options associated with this condition.
RESULTS
The results of this study highlight that despite the extremely low incidence of NAIT, it carries a high risk. Currently, there is no timely and effective prevention method available. However, using HPA-1a as a screening item for prenatal prevention shows the potential to reduce the mortality rate of NAIT fetuses. Further research is required to evaluate its accuracy and specificity.
CONCLUSIONS
The findings of this review emphasize the need for further research to develop effective prevention methods. The use of HPA-1a as a screening tool holds promise but requires additional investigation. Enhancing clinical understanding of NAIT will contribute to improved management and outcomes for affected infants.
Topics: Child; Infant; Infant, Newborn; Female; Pregnancy; Humans; Thrombocytopenia, Neonatal Alloimmune; Blood Platelets
PubMed: 37318890
DOI: No ID Found -
European Journal of Haematology Feb 2024The future of chimeric antigen receptor T (CAR-T) therapy remains unclear. New studies are constantly being published confirming the efficacy and favorable safety... (Review)
Review
The future of chimeric antigen receptor T (CAR-T) therapy remains unclear. New studies are constantly being published confirming the efficacy and favorable safety profile of its innovative enhancements. Currently approved CAR-T drugs are manufactured exclusively for a specific patient from the recipient's own cells. This does not close the door to further modifications with subsequent personalization and better adaptation to the individual needs. Bringing such a drug to market would involve raising the already high costs, so it is necessary to lower the existing ones. On the other hand, so-called universal CAR-T are also getting closer to the patient's bed, but its implementation may struggle with multiple challenges, including development of graft-versus-host disease (GvHD) and alloimmunity. However, that off-the-shelf therapy could prove useful as a quick solution for patients in very poor condition or excluded from current therapy due to manufacturing limitations. The introduction of currently tested solutions may undoubtedly change the current paradigm of treatment.
Topics: Humans; Receptors, Chimeric Antigen; T-Lymphocytes; Immunotherapy, Adoptive
PubMed: 37431655
DOI: 10.1111/ejh.14039 -
Immunological platelet transfusion refractoriness: current insights from mechanisms to therapeutics.Platelets Dec 2024Although there have been tremendous improvements in the production and storage of platelets, platelet transfusion refractoriness (PTR) remains a serious clinical issue... (Review)
Review
Although there have been tremendous improvements in the production and storage of platelets, platelet transfusion refractoriness (PTR) remains a serious clinical issue that may lead to various severe adverse events. The burden of supplying platelets is worsened by rising market demand and limited donor pools of compatible platelets. Antibodies against platelet antigens are known to activate platelets through FcγR-dependent or complement-activated channels, thereby rapidly eliminating foreign platelets. Recently, other mechanisms of platelet clearance have been reported. The current treatment strategy for PTR is to select appropriate and compatible platelets; however, this necessitates a sizable donor pool and technical assistance for costly testing. Consolidation of these mechanisms should be of critical significance in providing insight to establish novel therapeutics to target immunological platelet refractoriness. Therefore, the purposes of this review were to explore the modulation of the immune system over the activation and elimination of allogeneic platelets and to summarize the development of alternative approaches for treating and avoiding alloimmunization to human leukocyte antigen or human platelet antigen in PTR.
Topics: Humans; Platelet Transfusion; Blood Platelets; Thrombocytopenia; Antigens, Human Platelet; HLA Antigens
PubMed: 38314765
DOI: 10.1080/09537104.2024.2306983 -
Hematology, Transfusion and Cell Therapy 2024Sickle cell disease (SCD) is the most important hemoglobinopathy worldwide. The treatment often requires phenotype-matched red blood cell (RBC) transfusions, but...
INTRODUCTION
Sickle cell disease (SCD) is the most important hemoglobinopathy worldwide. The treatment often requires phenotype-matched red blood cell (RBC) transfusions, but alloimmunization to non-ABO antigens may occur in a part of the SCD patients. The genotyping has been used for RBC antigen prediction, reducing the possibility of the alloimmunization.
OBJECTIVE AND METHOD
In this study we performed the genotyping for the Kell and RHCE blood groups in samples from 77 phenotyped Brazilian SCD patients, whose alloimmunization profiles were also assessed.
RESULTS
Discrepancies between genotyping and phenotyping for the RHCE and Kell blood groups systems were observed in 22.07% (17/77) of the SCD patients. We found C/c and E/e discrepancies in 11.68% and 9.09% of patients, respectively; one SCD patient (1.3%) presented a discrepancy in the Kell group. Two SCD patients with discrepancies between genotype and phenotype were alloimmunized. In total, twenty-eight patients (36.4%) developed alloantibodies, of which 55.17% were directed against antigens in the Rh system, 8.62% were directed against antigens in the Kell system and 36.20%, against other groups. Finally, the frequency of discrepancies is significantly higher in non-alloimmunized patients (30.61%), compared to alloimmunized patients (7.14%) (p = 0.0217).
CONCLUSION
In part, the alloimmunization of the SCD patients may have been triggered by these discrepancies, indicating that the integration of serological and molecular tests in the immunohematology routine could help to increase the transfusion safety. However, the higher number of alloimmunized patients without discrepancies showed that reasons other than the discrepancies appear to have influenced more strongly the alloimmunization in the SCD patients in this study.
PubMed: 37344342
DOI: 10.1016/j.htct.2023.05.004 -
Transplantation Jul 2024Autophagy is a lysosome-dependent regulated mechanism that recycles unnecessary cytoplasmic components. It is now known that autophagy dysfunction may have a pathogenic... (Review)
Review
Autophagy is a lysosome-dependent regulated mechanism that recycles unnecessary cytoplasmic components. It is now known that autophagy dysfunction may have a pathogenic role in several human diseases and conditions, including kidney transplantation. Both defective and excessive autophagy may induce or aggravate several complications of kidney transplantation, such as ischemia-reperfusion injury, alloimmune response, and immunosuppressive treatment and side effects. Although it is still complicated to measure autophagy levels in clinical practice, more attention should be paid to the factors that may influence autophagy. In kidney transplantation, the association of low doses of a mammalian target of rapamycin inhibitor with low doses of a calcineurin inhibitor may be of benefit for autophagy modulation. However, further studies are needed to explore the role of other autophagy regulators.
Topics: Kidney Transplantation; Humans; Autophagy; Immunosuppressive Agents; Reperfusion Injury; Animals; Graft Rejection; Calcineurin Inhibitors; Kidney
PubMed: 37953477
DOI: 10.1097/TP.0000000000004862 -
The Journal of Pediatrics Dec 2023To understand better those factors relevant to the increment of rise in platelet count following a platelet transfusion among thrombocytopenic neonates.
OBJECTIVE
To understand better those factors relevant to the increment of rise in platelet count following a platelet transfusion among thrombocytopenic neonates.
STUDY DESIGN
We reviewed all platelet transfusions over 6 years in our multi-neonatal intensive care unit system. For every platelet transfusion in 8 neonatal centers we recorded: (1) platelet count before and after transfusion; (2) time between completing the transfusion and follow-up count; (3) transfusion volume (mL/kg); (4) platelet storage time; (5) sex and age of platelet donor; (6) gestational age at birth and postnatal age at transfusion; and magnitude of rise as related to (7) pre-transfusion platelet count, (8) method of enhancing transfusion safety (irradiation vs pathogen reduction), (9) cause of thrombocytopenia, and (10) donor/recipient ABO group.
RESULTS
We evaluated 1797 platelet transfusions administered to 605 neonates (median one/recipient, mean 3, and range 1-52). The increment was not associated with gestational age at birth, postnatal age at transfusion, or donor sex or age. The rise was marginally lower: (1) with consumptive vs hypoproductive thrombocytopenia (P < .001); (2) after pathogen reduction (P < .01); (3) after transfusing platelets with a longer storage time (P < .001); and (4) among group O neonates receiving platelets from non-group O donors (P < .001). Eighty-seven neonates had severe thrombocytopenia (<20 000/μL). Among these infants, poor increments and death were associated with the cause of the thrombocytopenia.
CONCLUSION
The magnitude of post-transfusion rise was unaffected by most variables we studied. However, the increment was lower in neonates with consumptive thrombocytopenia, after pathogen reduction, with longer platelet storage times, and when not ABO matched.
Topics: Humans; Infant, Newborn; Blood Platelets; Blood Transfusion; Platelet Count; Platelet Transfusion; Thrombocytopenia, Neonatal Alloimmune; Male; Female
PubMed: 37572863
DOI: 10.1016/j.jpeds.2023.113666 -
Transfusion Oct 2023We recently introduced a policy to use O positive red cells in emergency transfusions for males >16 years of age and females >50 years of age. Here, we investigate...
BACKGROUND
We recently introduced a policy to use O positive red cells in emergency transfusions for males >16 years of age and females >50 years of age. Here, we investigate changes in emergency transfusion practice and rates of red cell alloimmunization with the use of O positive blood for emergency transfusion.
STUDY DESIGN AND METHODS
State-wide retrospective review of emergency transfusions between June 2020 and June 2021. The laboratory information system and patient medical records were used to collect demographic details, indications for transfusion, usage of O positive and O negative blood and rates of alloimmunization.
RESULTS
There were 2354 red cell units transfused to 1013 patients (male = 59%, average age = 53 years) during the 12-month period. O positive units accounted for 46.9% (1103 units) of emergency transfusions. However, 726 (30.8%) O negative units were transfused to patients without a mandatory indication for O negative blood. Twenty-eight patients (2.9%) had a red cell alloantibody prior to transfusion including anti-E (n = 10), anti-D (n = 4), and anti-K (n = 4). One patient with prior anti-D had mild delayed hemolysis. There were 19 patients (4.3%, median follow-up 22 days) who developed a red cell alloantibody after emergency transfusion and include anti-E (n = 10), anti-D (n = 7), and anti-C (n = 5).
DISCUSSION
The use of O positive blood for emergency transfusion has saved 1103 O negative red cell units with no detriment to patient outcome. There remains potential to optimize use of O positive blood in emergency transfusion and to understand red cell alloimmunization rates in a prospective fashion.
PubMed: 37698202
DOI: 10.1111/trf.17537