Living Donor Liver transplantation in an alloimmunised patient: Immunological challenges and Management in Indian Settings.

Liver transplantation (LT) is often associated with hematological abnormalities with immune or non-immune etiologies and require timely diagnosis and interventions. We report a case of a patient suffering from non-alcoholic steato-hepatitis (NASH) related end stage liver disease (ESLD) with multiple red cell antibodies who underwent LT surgery. In postoperative phase, she developed immune hemolysis as well as acute antibody mediated rejection (AMR) which was managed with therapeutic plasma exchange and IVIG. The case highlights the need to develop an algorithm for red cell and HLA antibody screening in high-risk patients for timely detection and management.

Immunohematological challenges in COVID infected patients.

BACKGROUND: Several autoimmune disorders have been reported to be related with COVID infection. In continuation to these autoimmune phenomenon, autoimmune hemolytic anaemia (AIHA) also has been noted in COVID infected patients. The aim of the study was to find out the prevalence of red cell alloimmunization, ABO discrepancy and positive direct antiglobulin test (DAT) results in COVID infected patients hospitalised in a tertiary care centre in North India. METHODOLOGY: This was a retrospective observational study done from July 2020 to June 2021. All symptomatic patients admitted to ICU tested positive for SARS CoV-2 whose blood samples were received in the immunohematology laboratory of department of Transfusion Medicine for determination of blood group and issue of packed red cells, and found to have positive antibody screen, blood group discrepancy and positive DAT results, were included in the study. RESULTS: A total of 10,568 tests were run, out of which 4437 were for determination of blood group, 5842 were for antibody screen and 289 were for direct antiglobulin test. Included in this study were 146 patients who either had blood group discrepancy, or had a positive antibody screen or had a positive DAT. Out of 115 positive antibody screen, 66 patients had only alloantibodies, 44 patients had only autoantibodies while only 5 patients had both auto as well as alloantibodies. Total number of positive DAT cases was 50 (50/289 = 17.3 %). There were 26 ABO discrepancies (26/4437 =0.58 %) found. CONCLUSION: Our results also indicate that there is rise in rate of alloimmunization and DAT positivity among COVID patients.

Immunoserologic and hemotherapy considerations in patients undergoing hematopoietic progenitor cell transplantation

With increasing evidence of the success of hematopoietic progenitor cell (HPC) transplantation in the cure of many benign and malignant diseases, such interventions have been performed at increasing rates for the past several years. Due to myelosuppression caused by the conditioning and graft-versus-host disease (GVHD) prophylaxis regimens, blood component transfusions are almost inevitably needed. During transplantation, patient's hematopoietic lineages reconstitute to the HPC donor's progenitor cell types. Therefore, specific immunoserologic and hemotherapeutic aspects need to be considered for the selection of blood components during different phases of transplantation for successful outcomes. Those considerations include but are not limited to ABO and human leucocyte antigen (HLA) compatibility of the transfused blood components with either or both the patient and the HPC donor according to the particular phase of transplantation, and the special blood component processing to reduce the risk of transfusion associated graft-versus-host disease (TA-GVHD), cytomegalovirus (CMV) transmission in CMV seronegative patients and immune mediated platelets refractoriness. Complications may still arise, particularly in major, minor, or bidirectional ABO mismatched transplantations and/or due to the HLA mismatch and alloimmunization. Here we discuss the indications, immunoserologic considerations and the special component processing of red blood cells (RBCs), platelets, granulocytes, and plasma transfusions, based upon the current evidence and describe the prevention and management of salient, pertinent complications.Copyright © 2022 The authors.

Fetal Medicine Unit: Need of the Hour at Tertiary Care Centers in India?

Aim: The aim of the article was to emphasize the need for a fetal medicine unit at tertiary care hospitals. Background: The incidence of Rh-negative in India is 5–10%. The issue of Rh incompatibility arises when the mother is Rh-negative and the fetus is Rh-positive. Rh alloimmunization can lead to fetal anemia, hydrops fetalis, and even intrauterine death. It leads to perinatal loss of 1–2.5%. Fetal anemia is a serious complication in pregnancy and is associated with perinatal morbidity and mortality. Intrauterine transfusion (IUT) is a good treatment option for fetal anemia due to Rh incompatibility. Intravascular transfusion offers the best chance of survival to fetuses severely affected with Rh isoimmunization, overall survival exceeding 80%. In the cases with detectable antibodies, prenatal monitoring of maternal antibody titers and fetal middle cerebral arterial-peak systolic velocity (MCA-PSV) Doppler ultrasound assessment helps to plan fetal blood sampling and IUT procedures. Thus, the establishment of fetal medicine unit at tertiary care centers in India is need of the hour. Case description: We report a case of 32-year-old G4P3L1END1IUD1 with Rh-negative sensitized pregnancy with fetal anemia, managed successfully with IUT. Clinical significance: Early diagnosis of fetal anemia by serial MCA-PSV measurements and referral to fetal medicine unit are important for improving the outcome in Rh-negative sensitized pregnancies. Conclusion: Establishment of fetal medicine unit at tertiary care centers is the need of the hour to improve the fetal outcome in high-risk pregnancies like Rh-negative pregnancy.

Impact of COVID-19 on HLA alloimmunization in patients on the kidney transplant waiting list

The aim of this study was to determine the impact of coronavirus disease 2019 (COVID-19) on HLA alloimmunization in patients on the waiting list for kidney transplantation (KTWL) at the University Hospital Center Rijeka, Croatia. Our study group included 19 patients on the KTWL with known positive tests for COVID-19. Serum samples before the COVID-19 pandemic and after a positive COVID-19 test were tested as part of a routine quarterly assessment of HLA antibodies. Screening was performed using the complementdependent cytotoxicity method (CDC) and Luminexbased assays (Immucor, Inc.) in parallel. We analyzed and compared HLA antibody results before and after COVID-19 for each patient. Two (10.5%) patients required hospitalization for COVID-19, and all recovered from the infection. The results of the CDC test showed in 3 of 19 (15.8%) patients a significant rise in PRA after COVID infection. Out of 14 (73.7%) non-sensitized patients, one became positive, and in 2 of 5 (26.3%) sensitized patients post-COVID sera showed a 5 to 19-fold increase in PRA while in others the changes were insignificant. The specificity of HLA antibodies and MFIs measured by the Luminex single antigen tests remained largely unchanged in post-COVID samples compared to the corresponding pre-COVID samples. Only post- COVID sera in two patients with marked increase in PRA resulted in higher MFI values, but without changes in antibody profile. Our study did not demonstrate a significant effect of COVID-19 infection on HLA antibody status in patients awaiting kidney transplantation. However, post-COVID sera in a small proportion of patients showed a large increase in PRA. These suggests that the possibility of developing de novo or increasing the titer of existing HLA antibodies after COVID-19 infection should be considered during HLA antibody assessment of the patients on the waiting list for kidney transplantation.

Adverse Events Following COVID-19 Vaccination in Transfusion-Dependent -Thalassemia Patients

Introduction: Patients with transfusion-dependent-thalassemia (TDT) are considered as increased risk population for severe and/or morbid COVID-19 infection. Timely vaccination is the main preventive method for severe COVID-19. Different adverse events and reactions following vaccination have been reported, with severe ones being extremely rare. TDT patients may have altered immunity due to chronic transfusions, iron overload and chelation therapy, and splenic dysfunction. The safety profile of vaccination in chronically transfused patients with thalassemia has not been reported. AIM: To evaluate the safety profile of COVID-19 vaccines in TDT patients. Patients and Methods: This is a single institution's, retrospective analysis evaluating all TDT patients, older than 18 years old, who had completed the vaccination protocol at least 30 days before data cut-off time (July 20 th 2021). Adverse events were reported by patients up to 30 days post each dose. Demographic data and hematological data, including mean hemoglobin levels before and up to 30 days after each dose, were recorded. T-test was performed to investigate changes in hematological profile and transfusion burden post vaccination. Results: 186 patients (median age:45;range:18-61 years old;male/female:87/99) were included for data analysis corresponding to 53% of all TDT patients followed in our Thalassemia Unit. Distribution of vaccine types were: Comirnaty -BNT162b2 (Pfizer Inc. and BioNTech)90.86% (n =168), Vaxzevria (previously COVID-19 vaccine, AstraZeneca)1.61% (n=3), Moderna (Moderna TX Inc.)6.99% (n =13) and JNJ-78436735 (Janssen Pharmaceuticals Companies of Johnson & Johnson)0.54% (n =2). No patients had confirmed or suspected previous COVID-19 infection. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The incidence of adverse events after 1 st and 2 nd dose were 43.5% (81/186) and 54.8% (102/186), respectively. Adverse events after 1 st dose included pain at injection site 26.3%( n=49), fatigue 9.7%(n=18), fever 5.4% (n=10),headaches 4.3% (n=8), arthralgia and myalgia 2.2% (n=4), and lymphadenopathy 0.5% (n=1). Adverse events after 2 nd dose included fever 28.5% (n=53), fatigue 17.7% (n=33), pain at injection site 15.6%(n=29), arthralgia and myalgia 11.3% (n=21), headaches 9.1% (n=17), lymphadenopathy 3.2% (n=6), dizziness 0,5% (n=1), tachycardia 0.5% (n=1), diarrhea/ vomiting 0.05% (n=1) and amaurosis fugax 0.5%: (n=1). No grade 4-5 events or anaphylaxis were observed. Two patients (both males, 51 years and 45 years old, respectively) presented with acute hemolytic crisis with hemoglobinuria in 3 rd and 20 th day after the second dose with Pfizer/BioNTech, respectively. They are receiving treatment with corticosteroids without partial response. Both patients had a history of acute hemolysis crisis within the last 3 years. A decrease in Hb levels after either the first or second dose compared to pre-vaccination mean Hb levels was observed (mean=9.9 /sd=0.63 vs mean=9.44 /sd=0.76), (p < 0.001). Conclusions: Compared to the vaccine trials, we observed some lower incidence of vaccine-related adverse events in our cohort of TDT patients, which may be related to the less stringent reporting methods outside official trials. A temporary drop in hemoglobin levels may be noted in chronically transfusion patients, which parallels what is observed when patients are developing infection or inflammation. Of interest, two patients with previous history of alloimmunization, developed hemolysis. Close hematological follow up may be required in TDT patients post vaccination. The risk/benefit of the vaccination is strongly positive for this vulnerable population. Disclosures: Kattamis: Agios Pharmaceuticals: Consultancy;IONIS: Consultancy;VIFOR: Consultancy;CRISPR/Vertex: Consultancy, Honoraria;BMS/Celgene: Consultancy, Honoraria, Research Funding;Chiesi: Honoraria;Novartis: Consultancy, Honoraria, Research Funding;Amgen: Consultancy.

Altered type 1 interferon responses in alloimmunized and nonalloimmunized patients with sickle cell disease.

Patients with sickle cell disease (SCD) have a high prevalence of RBC alloimmunization. However, underlying mechanisms are poorly understood. Given that proinflammatory type 1 interferons (IFNα/ß) and interferon stimulated genes (ISGs) promote alloimmunization in mice, we hypothesized that IFNα/ß may contribute to the increased frequency of alloimmunization in patients with SCD. To investigate this, expression of ISGs in blood leukocytes and peripheral blood mononuclear cells (PBMCs) of previously transfused SCD patients with or without alloimmunization and race-matched healthy controls were quantified, and IFNα/ß gene scores were calculated. IFNα/ß gene scores of SCD leukocytes and plasma cytokines were elevated, compared to controls (gene score, p < 0.01). Upon stimulation with IFNß, isolated PBMCs from patients with SCD had elevated ISGs and IFNα/ß gene scores (p < 0.05), compared to stimulated PBMCs from controls. However, IFNß-stimulated and unstimulated ISG expression did not significantly differ between alloimmunized and non-alloimmunized patients. These findings indicate that patients with SCD express an IFNα/ß gene signature, and larger studies are needed to fully determine its role in alloimmunization. Further, illustration of altered IFNα/ß responses in SCD has potential implications for IFNα/ß-mediated viral immunity, responses to IFNα/ß-based therapies, and other sequelae of SCD.

The evolution of prenatal care delivery guidelines in the United States.

The coronavirus disease 2019 pandemic led to some of the most drastic changes in clinical care delivery ever seen in the United States. Almost overnight, providers of prenatal care adopted virtual visits and reduced visit schedules. These changes stood in stark contrast to the 12 to 14 in-person prenatal visit schedule that had been previously recommended for almost a century. As maternity care providers consider what prenatal care delivery changes we should maintain following the acute pandemic, we may gain insight from understanding the evolution of prenatal care delivery guidelines. In this paper, we start by sketching out the relatively unstructured beginnings of prenatal care in the 19th century. Most medical care fell within the domain of laypeople, and childbirth was a central feature of female domestic culture. We explore how early discoveries about "toxemia" created the groundwork for future prenatal care interventions, including screening of urine and blood pressure-which in turn created a need for routine prenatal care visits. We then discuss the organization of the medical profession, including the field of obstetrics and gynecology. In the early 20th century, new data increasingly revealed high rates of both infant and maternal mortalities, leading to a greater emphasis on prenatal care. These discoveries culminated in the first codification of a prenatal visit schedule in 1930 by the Children's Bureau. Surprisingly, this schedule remained essentially unchanged for almost a century. Through the founding of the American College of Obstetricians and Gynecologists, significant technological advancements in laboratory testing and ultrasonography, and calls of the National Institutes of Health Task Force for changes in prenatal care delivery in 1989, prenatal care recommendations continued to be the same as they had been in 1930-monthly visits until 28 weeks' gestation, bimonthly visits until 36 weeks' gestation, and weekly visits until delivery. However, coronavirus disease 2019 forced us to change, to reconsider both the need for in-person visits and frequency of visits. Currently, as we transition from the acute pandemic, we should consider how to use what we have learned in this unprecedented time to shape future prenatal care. Lessons from a century of prenatal care provide valuable insights to inform the next generation of prenatal care delivery.