Associations between ABO non-identical platelet transfusions and patient outcomes-A multicenter retrospective analysis.

BACKGROUND: Due to platelet availability limitations, platelet units ABO mismatched to recipients are often transfused. However, since platelets express ABO antigens and are collected in plasma which may contain ABO isohemagglutinins, it remains controversial as to whether ABO non-identical platelet transfusions could potentially pose harm and/or have reduced efficacy. STUDY DESIGN AND METHODS: The large 4-year publicly available Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) database was used to investigate patient outcomes associated with ABO non-identical platelet transfusions. Outcomes included mortality, sepsis, and subsequent platelet transfusion requirements. RESULTS: Following adjustment for possible confounding factors, no statistically significant association between ABO non-identical platelet transfusion and increased risk of mortality was observed in the overall cohort of 21,176 recipients. However, when analyzed by diagnostic category and recipient ABO group, associations with increased mortality for major mismatched transfusions were noted in two of eight subpopulations. Hematology/Oncology blood group A and B recipients (but not group O) showed a Hazard Ratio (HR) of 1.29 (95%CI: 1.03-1.62) and intracerebral hemorrhage group O recipients (but not groups A and B) showed a HR of 1.75 (95%CI: 1.10-2.80). Major mismatched transfusions were associated with increased odds of receiving additional platelet transfusion each post-transfusion day (through day 5) regardless of the recipient blood group. DISCUSSION: We suggest that prospective studies are needed to determine if specific patient populations would benefit from receiving ABO identical platelet units. Our findings indicate that ABO-identical platelet products minimize patient exposure to additional platelet doses.

Hemolytic anemia blunts the cytokine response to transfusion of older red blood cells in mice and dogs.

BACKGROUND: Transfusion of red blood cells (RBCs) stored for longer durations induces hemolysis and inflammatory cytokine production in murine and canine models. Despite immune system activation by stored RBCs, human randomized trials suggest that fresher RBC transfusions do not improve clinical outcomes. We hypothesized that underlying recipient hemolysis may affect cytokine responses to older RBC transfusions. STUDY DESIGN AND METHODS: C57BL/6 mouse cohorts were infused with anti-TER119 antibody to induce hemolysis, rabbit anti-platelet antiserum to induce immune thrombocytopenia (ITP), or appropriate control antibodies. Two days later, mice were transfused with fresh or stored RBCs. Furthermore, in a prospective, randomized, blinded trial, 38 client-owned dogs with primary autoimmune hemolytic anemia (AIHA) and two dogs with ITP, requiring RBC transfusion, were enrolled and randomized to receive fresh (≤7 days) or old (≥21 days) stored RBC transfusions. Monocyte chemoattractant protein (MCP)-1 levels were assessed at defined times after transfusion. RESULTS: Prior immune-mediated hemolysis blunted the MCP-1 response to stored RBC transfusion in mice (361 ± 111 pg/ml vs. 6836 ± 1528 pg/ml in mice with immune hemolysis vs. ITP, respectively; mean ± SD; p < .0001). Although hemolysis markers increased after transfusion of older RBCs, the cytokine response was also muted in dogs with AIHA. No differences in morbidity or mortality were evident comparing dogs randomized to fresh or old RBCs. CONCLUSION: These data suggest that underlying hemolysis blunts inflammatory responses to old RBC transfusions. The canine data support randomized trial results suggesting a lack of clinical benefit with fresh RBC transfusions in subjects with underlying, baseline hemolysis.

COVID-19 Mortality in a Pediatric Patient with Hemoglobin SC Disease and Alpha-Thalassemia Trait.

As the pandemic continues to evolve, more cases of COVID-19 in pediatric patients are being detected. A 12-year-old boy with HbSC disease alpha-thalassemia trait presented to a pediatric emergency room with fever and weakness. His vital signs were notable for fever, tachypnea, and tachycardia. His physical exam was concerning for increased work of breathing. He tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by PCR although his hemoglobin level remained near his baseline. His chest radiograph showed a retrocardiac opacity concerning for evolving acute chest syndrome. He decompensated quickly requiring invasive mechanical ventilation and exchange transfusion. He received hydroxychloroquine, broad-spectrum antibiotics, and enoxaparin for DVT prophylaxis. Despite showing clinical signs of improvement, he became acutely hypoxemic and suffered a cardiac arrest. We believe this to be an unusual case of a pediatric patient with HbSC disease and COVID-19. We outline clearly the course of illness and treatments trialed, which can prove beneficial to providers facing similar challenges as this virus continues to strike areas around the world. Although children have significantly better outcomes than adults, providers must remain vigilant while treating any patient with a hemoglobinopathy in the setting of severe COVID-19.

Biological and Clinical Factors contributing to the Metabolic Heterogeneity of Hospitalized Patients with and without COVID-19.

The Corona Virus Disease 2019 (COVID-19) pandemic represents an ongoing worldwide challenge. Exploratory studies evaluating the impact of COVID-19 infection on the plasma metabolome have been performed, often with small numbers of patients, and with or without relevant control data; however, determining the impact of biological and clinical variables remains critical to understanding potential markers of disease severity and progression. The present large study, including relevant controls, sought to understand independent and overlapping metabolic features of samples from acutely ill patients (n = 831), testing positive (n = 543) or negative (n = 288) for COVID-19. High-throughput metabolomics analyses were complemented with antigen and enzymatic activity assays on 831 plasma samples from acutely ill patients while in the emergency department, at admission, and during hospitalization. We then performed additional lipidomics analyses of the 60 subjects with the lowest and highest body mass index, either COVID-19 positive or negative. Omics data were correlated to detailed data on patient characteristics and clinical laboratory assays measuring coagulation, hematology and chemistry analytes. Significant changes in arginine/proline/citrulline, tryptophan/indole/kynurenine, fatty acid and acyl-carnitine metabolism emerged as highly relevant markers of disease severity, progression and prognosis as a function of biological and clinical variables in these patients. Further, machine learning models were trained by entering all metabolomics and clinical data from half of the COVID-19 patient cohort and then tested on the other half yielding ~ 78% prediction accuracy. Finally, the extensive amount of information accumulated in this large, prospective, observational study provides a foundation for follow-up mechanistic studies and data sharing opportunities, which will advance our understanding of the characteristics of the plasma metabolism in COVID-19 and other acute critical illnesses.

Biological and Clinical Factors Contributing to the Metabolic Heterogeneity of Hospitalized Patients with and without COVID-19.

The Corona Virus Disease 2019 (COVID-19) pandemic represents an ongoing worldwide challenge. The present large study sought to understand independent and overlapping metabolic features of samples from acutely ill patients (n = 831) that tested positive (n = 543) or negative (n = 288) for COVID-19. High-throughput metabolomics analyses were complemented with antigen and enzymatic activity assays on plasma from acutely ill patients collected while in the emergency department, at admission, or during hospitalization. Lipidomics analyses were also performed on COVID-19-positive or -negative subjects with the lowest and highest body mass index (n = 60/group). Significant changes in amino acid and fatty acid/acylcarnitine metabolism emerged as highly relevant markers of disease severity, progression, and prognosis as a function of biological and clinical variables in these patients. Further, machine learning models were trained by entering all metabolomics and clinical data from half of the COVID-19 patient cohort and then tested on the other half, yielding ~78% prediction accuracy. Finally, the extensive amount of information accumulated in this large, prospective, observational study provides a foundation for mechanistic follow-up studies and data sharing opportunities, which will advance our understanding of the characteristics of the plasma metabolism in COVID-19 and other acute critical illnesses.

The Impact of Age and BMI on the VWF/ADAMTS13 Axis and Simultaneous Thrombin and Plasmin Generation in Hospitalized COVID-19 Patients.

Aging and obesity independently contribute toward an endothelial dysfunction that results in an imbalanced VWF to ADAMTS13 ratio. In addition, plasma thrombin and plasmin generation are elevated and reduced, respectively, with increasing age and also with increasing body mass index (BMI). The severity risk of Corona Virus Disease 2019 (COVID-19) increases in adults older than 65 and in individuals with certain pre-existing health conditions, including obesity (>30 kg/m2). The present cross-sectional study focused on an analysis of the VWF/ADAMTS13 axis, including measurements of von Willebrand factor (VWF) antigen (VWF:AG), VWF collagen binding activity (VWF:CBA), Factor VIII antigen, ADAMTS13 antigen, and ADAMTS13 activity, in addition to thrombin and plasmin generation potential, in a demographically diverse population of COVID-19 negative (-) (n = 288) and COVID-19 positive (+) (n = 543) patient plasmas collected at the time of hospital presentation. Data were analyzed as a whole, and then after dividing patients by age (<65 and ≥65) and independently by BMI [<18.5, 18.5-24.9, 25-29.9, >30 (kg/m2)]. These analyses suggest that VWF parameters (i.e., the VWF/ADAMTS13 activity ratio) and thrombin and plasmin generation differed in COVID-19 (+), as compared to COVID-19 (-) patient plasma. Further, age (≥65) more than BMI contributed to aberrant plasma indicators of endothelial coagulopathy. Based on these findings, evaluating both the VWF/ADAMTS13 axis, along with thrombin and plasmin generation, could provide insight into the extent of endothelial dysfunction as well as the plasmatic imbalance in coagulation and fibrinolysis potential, particularly for at-risk patient populations.

Overview of Plasma and Platelet Transfusions in Critically Ill Children.

Critically ill children are a unique population who frequently receive plasma and platelet transfusions for both active bleeding and mitigation of bleeding risk. While these products are frequently administered, transfusion indications in this population remain unclear, and practice varies across institutions and providers. In this manuscript, we will outline the current evidence regarding plasma and platelet transfusions for hemostasis in the pediatric intensive care setting. For both products, we will describe the product composition, epidemiology, and product indications and discuss the potential risks and benefits involved with the transfusion. We will also discuss knowledge gaps and future areas of research.

What is new in paediatric medication safety?

Medication-related errors are among the most common medical errors, and studies have shown that the paediatric population is particularly vulnerable. Errors can occur during any step in the medication process. This review article seeks to highlight new advancements in the field of paediatric medication safety at each stage of the medication process, from ordering and transcribing to medication dispensing and administration. We will focus on interventions that are increasingly widely used, such as computerised provider order entry with clinical decision support, barcoding technologies and safe medication administration through technologies pumps (SMART pumps), as well as innovative mobile application devices and workflow management systems that are being piloted at single institutions. By highlighting what is new in paediatric medication safety, as well as the gaps that remain, we hope to continue to foster focus on this critically important area in order to create the safest possible environment for children.

Obtaining research biopsies during pediatric colonoscopy: Safety and adverse events.

AIM: To investigate the safety profile of acquiring additional intestinal biopsies for research purposes in children undergoing a medically indicated colonoscopy. METHODS: A retrospective review of 122 pediatric patients who underwent colonoscopy over a 9 mo time period was completed. 38/122 participants consented to a research study in which 4 additional biopsies were obtained, in addition to routine biopsies. The outcomes after colonoscopy were measured in the research participants, and compared to 84 control participants who did not consent for the study. Groups were compared with regard to number of biopsies obtained, underlying diagnosis, and both serious and minor adverse outcomes. Data was collected including: age, gender, race, indication, diagnosis, number of biopsies obtained per case and post procedure adverse events. Medical records were reviewed and a questionnaire was completed by each of the ten gastroenterologists who performed procedures during the study. Physicians were asked about individual patient outcomes to ensure that all adverse events, such as perforation, excessive bleeding, infection, and minor gastrointestinal outcomes, were captured and included. RESULTS: The research group had more biopsies obtained (mean = 13.58 ± 4.21) compared to controls (mean = 9.33 ± 4.40), P ≤ 0.0001, however there was no difference in adverse events. Serious outcomes, defined as perforation, bleeding and infection, did not occur, in either group. As such, the relationship between serious adverse events and number of biopsies obtained was not determined. Minor gastrointestinal outcomes, such as abdominal pain, diarrhea or vomiting, were reported in 21 patients (8 research participants and 13 control participants) however the incidence of minor gastrointestinal outcomes between the two groups did not vary significantly, P = 0.45. Additionally, the mean number of biopsies obtained in patients who had a minor outcome (mean = 12.1 ± 0.77), compared to those with no adverse outcome (mean = 10.34 ± 0.5), revealed no statistical difference between the groups (P = 0.12), suggesting that number of biopsies is not associated with incidence of minor adverse events. CONCLUSION: Patients participating in research requiring acquisition of additional biopsies for research purposes alone, are not at an increased risk of adverse outcomes.