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Transfusion Jun 2024Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) results from maternal platelet alloimmunization against paternal antigens inherited by the fetus, most often due...
BACKGROUND
Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) results from maternal platelet alloimmunization against paternal antigens inherited by the fetus, most often due to the Human Platelet Antigen (HPA)-1 system in Caucasians. We investigated in 2023, a 30-year-old Caucasian woman Gravida 2 Para 1 who gave birth at 35 weeks of gestation to a male (body weight 2210 g) without signs of bleeding. A severe thrombocytopenia (platelet count at 3 G/L) was discovered incidentally a few hours after delivery in the context of the management of a respiratory distress. The newborn recovered after one platelet concentrate transfusion and normalized his platelet count at Day 5.
STUDY DESIGN AND METHODS
FNAIT investigation was performed according to guideline recommendations. Platelet genotyping was carried out by multiplex PCR. Maternal serological investigation included Monoclonal Antibody-specific Immobilization of Platelet Antigens method (MAIPA) and Luminex technology.
RESULTS
Parental and newborn genotyping pointed out an HPA-4 incompatibility between the mother and the newborn and the father. Serological investigation revealed an anti-HPA-4b alloantibody confirming the diagnosis of neonatal alloimmune thrombocytopenia.
CONCLUSION
We described the third case of anti-HPA-4b alloantibody discovered in a Caucasian mother. This case strengthens the need for reference laboratory to genotype a panel of HPA alleles reflecting local genetic population diversity and for crossmatch of maternal serum with fresh paternal platelets in clinical suspected cases of neonatal alloimmune thrombocytopenia.
Topics: Humans; Isoantibodies; Thrombocytopenia, Neonatal Alloimmune; Female; Antigens, Human Platelet; Infant, Newborn; Adult; Pregnancy; Male; Platelet Transfusion; White People
PubMed: 38693097
DOI: 10.1111/trf.17863 -
The Journal of Pediatrics Apr 2024To develop neonate-specific prediction models for survival with native liver (SNL) in neonatal acute liver failure (ALF) and to determine if these prediction models have...
Establishing Neonate-specific Prognostic Markers in Acute Liver Failure: Admission Alpha Fetoprotein and Novel Neonatal Acute Liver Failure Scores Predict Patient Outcomes.
OBJECTIVE
To develop neonate-specific prediction models for survival with native liver (SNL) in neonatal acute liver failure (ALF) and to determine if these prediction models have superior accuracy to existing models for older children with ALF.
STUDY DESIGN
A single-center, retrospective chart review was conducted on neonates ≤ 30 days of life between 2005 and 2022 with ALF (international normalized ratio ≥ 2 or prothrombin time ≥ 20s and liver dysfunction). Statistical analysis included comparison of patients by outcome of SNL and generalized linear modeling to derive prediction models. The predictive accuracy of variables was evaluated by receiver operating characteristic (ROC) analysis and Kaplan-Meier survival analysis.
RESULTS
A total of 51 patients met inclusion criteria. The most common causes of neonatal ALF included ischemia (22%), infection (20%), and gestational alloimmune liver disease (16%). Overall SNL rate was 43% (n = 22). Alpha fetoprotein levels were higher in SNL patients (P = .034) and differed more significantly by SNL status among nongestational alloimmune liver disease patients (n = 21, P = .001). An alpha fetoprotein < 4775 ng/mL had 75% sensitivity and 100% specificity to predict death or transplant in nongestational alloimmune liver disease patients with an area under the ROC curve of 0.81. A neonate-specific admission model (international normalized ratio and ammonia) and peak model (prothrombin time and ammonia) also predicted SNL with good accuracy (area under the ROC curve = 0.73 and 0.82, respectively).
CONCLUSIONS
We identified neonate-specific prognostic variables for SNL in ALF. Findings from our study may help early risk stratification to guide medical decision-making and consideration for liver transplantation.
PubMed: 38692563
DOI: 10.1016/j.jpeds.2024.114080 -
European Journal of Pediatrics Apr 2024Neonatal acute liver failure (NALF), as a rare disease with high mortality, has limited relevant literature reports in China. We attempted to analyze a NALF cohort to...
Neonatal acute liver failure (NALF), as a rare disease with high mortality, has limited relevant literature reports in China. We attempted to analyze a NALF cohort to improve the prognosis of this disease. We included all patients diagnosed with NALF at our institution between 2016 and 2021 and retrospectively reviewed their electronic records. NALF was defined as an INR ≥ 2.0 due to liver disease 28 days after birth. Comparisons were made according to etiology and outcome. The Kaplan-Meier method was used to estimate survival. Fifty-eight patients were included in this study. Etiologies included hypoxic/ischemic injury (29.3%), infection (27.6%), gestational alloimmune liver disease with neonatal hemochromatosis (GALD-NH) (10.3%), inherited metabolic diseases (5.2%), hemophagocytic lymphohistiocytosis (1.7%), other etiologies (12.1%), and unidentified causes (13.8%). Enteroviruses constituted 87.5% of the viral infections, whereas herpes simplex virus accounted for no infections. The median INR was significantly lower in the infection group than in the GALD-NH group (P < 0.05 for multiple comparisons). At the last follow-up, none of the patients had undergone liver transplantation, and the overall mortality rate was 50%. Liver function completely recovered in 31% of the patients, all of whom survived. The overall median survival time was 48 days; 26 days for hypoxic/ischemic injury and 43 days for GALD-NH. The incidence of cholestasis was significantly greater among surviving patients (P = 0.018). Conclusion: Hypoxic/ischemic injury and infection are the predominant etiologies of NALF in China. The overall prognosis of NALF is poor, but its short-term prognosis is determined by the etiology. What is Known: • Neonatal acute liver failure (NALF) is a rare disorder with limited cohort studies, especially in China. • Gestational alloimmune liver disease, viral infections (especially herpes simplex virus), metabolic diseases and ischemic insults are common etiologies of NALF, which are significantly different from other populations. • There are no reliable biochemical markers to predict the outcome of NALF. What is New: • In this first report on a Chinese NALF cohort, we demonstrate that hypoxic/ischemic injury and infection (excluding herpes simplex virus) are the predominant etiologies of NALF. • The overall prognosis of NALF is poor, and its etiology determines the short-term outcome.
PubMed: 38689183
DOI: 10.1007/s00431-024-05567-7 -
Cureus Mar 2024Patients with myelodysplastic syndrome (MDS) often need platelet transfusions to address thrombocytopenia. The risk of alloimmunization, particularly in Rhesus (Rh)...
Patients with myelodysplastic syndrome (MDS) often need platelet transfusions to address thrombocytopenia. The risk of alloimmunization, particularly in Rhesus (Rh) incompatibility between donors and recipients during platelet transfusions, is heightened, especially with whole blood-derived pooled platelets as opposed to apheresis platelets. Although the occurrence of alloimmunization from platelet transfusions is minimal, there is an ongoing debate about whether Rh immune globulin (RhIg) should be administered to Rhesus D (RhD)-negative recipients of RhD-positive platelet units. We present a unique case of anti-D alloimmunization in a 56-year-old patient with underlying MDS following multiple platelet transfusions but never received packed cell transfusion or anti-D immunoglobulin. Some studies advocate for RhIg administration in specific scenarios and for certain patient populations. This case underscores the importance of considering Rhesus compatibility or administering anti-D immunoglobulin in cases where frequent platelet transfusions are required.
PubMed: 38681415
DOI: 10.7759/cureus.57165 -
Journal of Clinical Medicine Apr 2024The novel coronavirus disease 2019 (COVID-19) has led to significant morbidity and mortality among kidney transplant recipients. SARS-CoV-2 has been hypothesized to...
The novel coronavirus disease 2019 (COVID-19) has led to significant morbidity and mortality among kidney transplant recipients. SARS-CoV-2 has been hypothesized to cause an unusual immunological dysregulation triggering alloimmunity and leading to graft rejection. This prospective observational cohort study assessed 321 kidney transplant recipients who had COVID-19 infection. After the infection, patients' sera were tested for the presence of anti-HLA de novo DSA and non-DSA specificities. Logistic regression analysis and a stepwise multivariable logistic regression analysis were used to analyze the independent risk factors associated with the development of antibodies, adjusting for known confounders. The variables evaluated were acute COVID-19 characteristics (i.e., presentation, and need for hospitalization), demographic characteristics (i.e., age, gender, and primary renal disease), clinical characteristics (i.e., various comorbidities), and post-COVID-19 sequelae. Anti-HLA de novo DSA developed in 18.7% of patients, while anti-HLA class I and class II non-DSA antibodies developed de novo in 84 (26.3%) and 83 (25.9%) patients, respectively. The development of DSA, HLA-DQ, and HLA-DR antibodies was predicted by the history of graft rejection. Obesity appeared to be protective against the emergence of de novo DSA. De novo DSA and HLA-DR antibody formation was positively linked with intravenous immunoglobulin use, CMV-hyperimmune globulin use, and decreased doses of immunosuppression during acute infection. Better allograft function during the acute disease was a protective factor against the formation of HLA-DQ and HLA-DR antibodies. Positive predictors of de novo DSA development were graft biopsy and the reactivation of EBV after infection. These findings suggest that the SARS-CoV-2 virus has an immunomodulatory effect and may be associated with an increased mortality in this population.
PubMed: 38673655
DOI: 10.3390/jcm13082383 -
Blood Advances Apr 2024Hemolytic disease of fetus and newborn (HDFN) is a life-threatening disease mediated by maternal alloimmunization to red blood cell (RBC) antigens. Studies of maternal...
Hemolytic disease of fetus and newborn (HDFN) is a life-threatening disease mediated by maternal alloimmunization to red blood cell (RBC) antigens. Studies of maternal alloimmunization prevalence in the United States (U.S.) lack national data. This study describes prevalence and trends in alloimmunization in pregnancy in the U.S. RBC antibodies (abs) were identified in a large, nationwide, commercial laboratory database from 2010-2021. The cohort comprised pregnancies for which the year of lab collection and patient's state of residence were available. Data were normalized based on U.S. Centers for Disease Control and Prevention estimates of live births and weighted by year and U.S. Census Division. Cochrane-Armitage tests assessed temporal trends of alloimmunization. Of 9,876,196 pregnancies, 1.5% (147,262) screened positive for RBC abs, corresponding to an estimated prevalence of 1,518/100,000 pregnancies. Of identified RBC abs, anti-D comprised 64.1% (586/100,000 pregnancies). Prevalence of other high-risk RBC abs for HDFN included anti-K (68/100,000) and anti-c (29/100,000). Incidence of all three high-risk abs increased from 2010-21 (all p<0.001). Among almost 10 million pregnancies in the US, comprising an estimated 14.4% of all pregnancies, 1.5% screened positive for RBC abs. Almost three-quarters (74.3%; 683/100,000) of RBC abs identified were high-risk for HDFN. Though prevalence of anti-D is difficult to interpret without the ability to distinguish alloimmunization from passive immunity, it remains problematic in HDFN, ranking second only to anti-K in critical titers. Given the sequelae of HDFN, new initiatives are required to reduce the incidence of alloimmunization in patients of reproductive potential.
PubMed: 38662646
DOI: 10.1182/bloodadvances.2023012241 -
Pediatric Blood & Cancer Jul 2024
Topics: Humans; Male; Infant, Newborn; Thrombocytopenia, Neonatal Alloimmune; HLA Antigens; Isoantibodies; Anemia, Hemolytic, Autoimmune
PubMed: 38650178
DOI: 10.1002/pbc.31023 -
Pathologie (Heidelberg, Germany) Jul 2024The Banff Foundation produces recommendations for classifying various lesions in renal allografts. Experts gather to update the classification every other year based on... (Review)
Review
BACKGROUND
The Banff Foundation produces recommendations for classifying various lesions in renal allografts. Experts gather to update the classification every other year based on new scientific and clinical evidence.
OBJECTIVES
This article presents the most important changes incorporated into the new recommendations after the last Banff conference.
MATERIALS AND METHODS
The author of this article personally took part in the Banff conference and the subsequent survey, reported on the activities of a Banff working group (peritubular capillaritis) on-site, and contributed to drafting the recently published meeting report.
RESULTS
Lesions of antibody-mediated kidney allograft rejection (AMR), especially microvascular inflammation, have been part of the diagnostic algorithm for over 20 years. Experts advocated for a simplified AMR algorithm and mindful inclusion of molecular pathological data in the clinicopathological reflection regarding therapeutic decision. A new, more descriptive diagnostic entity-microvascular inflammation, C4d negative and DSA negative-has been introduced into the AMR category to acknowledge this histological constellation and motivate research into this pathophysiologically and immunologically probably different phenotype.
CONCLUSIONS
The Banff classification provides a structure for diagnosing kidney transplant pathology. Regular updates serve to adapt to ever-growing knowledge about alloimmunity. Particular challenges are capturing the complexity of various immunological scenarios and ensuring an understandable representation of these in a pathology report.
Topics: Kidney Transplantation; Humans; Graft Rejection; Allografts; Inflammation; Kidney; Microvessels
PubMed: 38649466
DOI: 10.1007/s00292-024-01328-3 -
BioRxiv : the Preprint Server For... Apr 2024Regulatory T cells (Tregs) have potential as a cell-based therapy to prevent or treat transplant rejection and autoimmunity. Using an HLA-A2-specific chimeric antigen...
Regulatory T cells (Tregs) have potential as a cell-based therapy to prevent or treat transplant rejection and autoimmunity. Using an HLA-A2-specific chimeric antigen receptor (A2-CAR), we previously showed that adoptive transfer of A2-CAR Tregs limited anti-HLA-A2 alloimmunity. However, it was unknown if A2-CAR Tregs could also limit immunity to autoantigens. Using a model of HLA-A2 islet transplantation into immunodeficient non-obese diabetic mice, we investigated if A2-CAR Tregs could control diabetes induced by islet-autoreactive (BDC2.5) T cells. In mice transplanted with HLA-A2 islets, A2-CAR Tregs reduced BDC2.5 T cell engraftment, proliferation and cytokine production, and protected mice from diabetes. Tolerance to islets was systemic, including protection of the HLA-A2 endogenous pancreas. In tolerant mice, a significant proportion of BDC2.5 T cells gained FOXP3 expression suggesting that long-term tolerance is maintained by Treg generation. Thus, A2-CAR Tregs mediate linked suppression and infectious tolerance and have potential therapeutic use to simultaneously control both allo- and autoimmunity in islet transplantation.
PubMed: 38645184
DOI: 10.1101/2024.04.06.588414 -
Transfusion May 2024Glanzmann thrombasthenia (GT) and Bernard-Soulier syndrome (BSS) patients require frequent platelet transfusions and hence have an increased risk for alloimmunization...
Should HLA and HPA-matched platelet transfusions for patients with Glanzmann Thrombasthenia or Bernard-Soulier syndrome be standardized care? A Dutch survey and recommendations.
BACKGROUND
Glanzmann thrombasthenia (GT) and Bernard-Soulier syndrome (BSS) patients require frequent platelet transfusions and hence have an increased risk for alloimmunization against donor Human Leukocyte Antigens (HLA) when no HLA-matching is performed. Knowing that Human Platelet Antigens (HPA) are located on the platelet glycoproteins that can be absent in these patients, preventive HPA-matching may also be considered. Uniform recommendations on this topic lack in transfusion guidelines making standard practice unclear, therefore, we aimed to provide a framework for matched platelet transfusions.
STUDY DESIGN AND METHODS
We conducted a targeted literature search and a national survey of Dutch (pediatric) hematologists from July to September 2021.
RESULTS
We found 20 articles describing platelet transfusion policies in 483 GT-patients and 29 BSS-patients, both adults and children. Twenty surveys were returned for full analysis. All responders treated patients with platelet disorders, including GT (n = 36 reported) and BSS (n = 29 reported). Of respondents, 75% estimated the risk of antibody formation as "likely" for HLA and 65% for HPA. Formation of HLA antibodies was reported in 5 GT and in 5 BSS-patients, including one child. Fifteen respondents gave preventive HLA-matched platelets in elective setting (75%). Three respondents additionally matched for HPA in GT-patients (15%). Main argument for matched platelet transfusions was preventing alloimmunization to safeguard the effectivity of 'random' donor-platelets in acute settings.
CONCLUSION
Elective HLA-matching for GT and BSS-patients is already conducted by most Dutch (pediatric) hematologists. HPA-matching is mainly applied when HPA-antibodies are formed. Based on the current literature and the survey, recommendations are proposed.
Topics: Humans; Platelet Transfusion; Antigens, Human Platelet; Thrombasthenia; Bernard-Soulier Syndrome; Netherlands; HLA Antigens; Surveys and Questionnaires; Male; Female; Child
PubMed: 38642032
DOI: 10.1111/trf.17824