Editor: Deborah Sesok-Pizzini, MD, MBA, chief medical officer, Labcorp Diagnostics, Burlington, NC, and adjunct professor, Department of Clinical Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Association of epsilon aminocaproic acid with acute kidney injury after hemorrhage in children
May 2024—Massive hemorrhage is a major cause of death in children, and the mortality rate from life-threatening hemorrhage is estimated to be 20 to 51 percent. To counter this high mortality rate, clinicians have sought to standardize massive transfusion protocols and hemostatic resuscitation, ensuring that protocols support balanced blood-based resuscitation or the use of low titer group O whole blood, or both. These protocols may include using the lysine analogue antifibrinolytics tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) in children with life-threatening hemorrhage (LTH). However, use of these antifibrinolytics is much more common in adult trauma patients. Study data suggest that TXA may increase survival outcomes in adults with traumatic injury, postpartum hemorrhage, nontraumatic intracranial hemorrhage, and all-cause bleeding. Pediatric studies have reported an association with improved 24-hour survival for patients who receive TXA during an LTH event. In addition to LTH being linked to high mortality, it is associated with such adverse events as acute kidney injury, acute respiratory distress syndrome (ARDS), and sepsis following LTH. No data are available about whether to use EACA or TXA in pediatrics or which of them results in fewer adverse events. The authors conducted a secondary analysis of the Massive Transfusion in Children (MATIC) database to further investigate any association that EACA, TXA, and no therapy have with risk of such adverse events as acute kidney injury, ARDS, and sepsis. Of the original 449 children in the MATIC data set, only 448 met the criteria for the authors’ study since the one patient receiving EACA and TXA therapy was excluded. The patients’ bleeding was categorized as 46 percent trauma, 34 percent operative, and 20 percent medical related. Eighty-eight percent of the patients did not receive antifibrinolytic medication, eight percent received TXA, and five percent received EACA. The study found that 17.1 percent of patients in the no antifibrinolytics group developed acute kidney injury, as did 16.2 percent in the TXA group and 50 percent in the EACA group (p=.002). After adjusting for cardiothoracic surgery, cyanotic heart disease, pre-existing renal disease, and lowest hemoglobin pre-LTH, the EACA group had an increased risk of acute kidney injury (adjusted odds ratio, 3.3 [95 percent confidence interval, 1.0–10.3]) compared with those receiving no antifibrinolytics. However, TXA was not associated with such injury. Sepsis and ARDS was not associated with either antifibrinolytic treatment. The authors concluded that administering EACA during LTH increased the risk of acute kidney injury in patients with operative bleeding and approached significance with bleeding caused by trauma. However, EACA did not change adverse risks with medical bleeding. The authors recommend additional studies to compare the risk of acute kidney injury between pediatric patients receiving EACA and TXA.
Kolodziej JH, Leeper CM, Leonard JC, et al. Epsilon aminocaproic acid is associated with acute kidney injury after life-threatening hemorrhage in children. Transfusion. 2023;63:S20–S34. doi:10.1111/trf.17373
Correspondence: Dr. Julia H. Kolodziej at kolodziejj@wustl.edu
Safety of administering LTOWB to children weighing less than 20 kilograms
Low titer group O whole blood has gained popularity as the initial resuscitative fluid for massive bleeding in adults and children. Several studies of adult and pediatric trauma have shown that low titer group O whole blood (LTOWB) has such benefits as ease of administration, efficiency in achieving balanced resuscitation, fewer donor exposures, receipt of cold stored platelets, and a lower 24-hour blood product requirement following its transfusion. A theoretical risk associated with transfusion of LTOWB is hemolysis of anti-A or anti-B if a person’s blood type is unknown and LTOWB is administered to non-O blood group recipients. To prevent this hemolytic reaction, each transfusing institution and blood supplier of LTOWB must determine what qualifies as low whole blood titers. Of particular concern is the pediatric population, for which variable size, weight, and circulating blood volume occur across an age spectrum of patients. Some centers limit the transfusion of LTOWB to children of a specific age and weight to ensure these patients have sufficient blood volume to dilute incompatible antibodies. Although data support the safety and efficacy of LTOWB for pediatric patients, few studies address safety in the youngest and smallest LTOWB recipients. The authors of this study evaluated the safety of using LTOWB in pediatric massively bleeding patients weighing less than 20 kg. Their single-center retrospective cohort study of pediatric recipients of RhD-negative LTOWB who weighed less than 20 kg ran from June 2016 to October 2022. The investigators searched a hospital transfusion service database to identify patients who fit the study criteria. Data from the hospital’s trauma database and electronic medical record were then merged with the transfusion data, including basic patient demographics, injury severity score, component abbreviated injury scale scores, admission vital signs, and laboratory test results. The latter were for lactate dehydrogenase, total bilirubin, haptoglobin, reticulocyte count, serum potassium, and creatinine. The main outcome of the study was an analysis of the biochemical markers for hemolysis and renal function and the occurrence of transfusion reactions. Other clinical outcomes included 28-day mortality, hospital length of stay, intensive care unit length of stay, length of mechanical ventilation, and total 24-hour transfusion volume. The non-group O LTOWB recipients were compared with the group O LTOWB recipients. The data showed that for 21 children, the median weight was 12 kg and the median age was three years. The most common indication for transfusion was trauma. The median volume of LTOWB transfused was 30 mL/kg. There were nine non-group O and 12 group O recipients. No statistically significant difference in the median concentrations of any of the biochemical markers of hemolysis or renal function was found between these two groups and the three time points. Furthermore, no significant differences in demographic data, clinical outcomes, or reported transfusion reactions were noted between the two study groups. The authors concluded that the data suggest that LTOWB is safe for children weighing less than 20 kg. Additional multi-center studies involving larger cohorts are needed to confirm this single-center result for pediatric patients receiving LTOWB. These studies would need to strictly adhere to massive transfusion protocols and monitoring practices for hemolysis and renal function.
Khalil EA, Gaines BA, Morgan KM, et al. Receipt of low titer group O whole blood does not lead to hemolysis in children weighing less than 20 kilograms. Transfusion. 2023;63:S18–S25. doi:10.1111/trf.17327
Correspondence: Dr. Christine M. Leeper at leepercm@upmc.edu