Hyperkalemia: The Trojan horse of pediatric transfusion?

Transfusion practice in neonatal and pediatric patients differs from the practice in adults due to physiologic changes that take place during the transition from fetus to adolescent. Blood volume, hematologic values, immune system maturity, and physiologic responses to hypovolemia and hypoxia vary widely in this heterogeneous population, adding to the complexity of pediatric transfusion practice. When transfusing pediatric patients, tailored administration and exchange transfusion protocols are required to provide transfusion support in specific diseases or unique neonatal and pediatric situations. Special processing is often required to prevent adverse effects of transfusion in pediatric recipients. Detailed epidemiologic and clinical data on pediatric transfusion practice are scarce, as few national transfusion services provide age-aggregated data. In 2016, Patel noted the lack of a detailed neonatal red blood cell (RBC) transfusion data set in the United States. Bowen linked population-based birth and hospital data from New South Wales between 2001 and 2011 to determine rates of transfusion in the first 28 days of life. During that time, 4.8 per 1000 neonates received an RBC transfusion and 0.3 per 1000 an exchange transfusion. Blood product use remained at a very high frequency in preterm neonates born at less than 30 weeks' gestation. In a retrospective cohort study of preterm neonates born before 30 weeks' gestation who were admitted to neonatal intensive care units in the Canadian Neonatal Network from 2004 to 2012, 8252 (56%) of 14,868 eligible neonates received 2151 RBCs. Finally, in a 2009 UK study, New described RBC transfusion in hospitalized children less than 18 years during a 3-month observation period. A total of 1302 pediatric patients were transfused. A total of 74% of patients received a single RBC transfusion during their admission; more than half of recipients had a cancer diagnosis. Patterns of blood use among countries show striking differences. According to the World Health Organization, in low-income countries, up to 54% of blood transfusions are given to children under 5 years of age, while in highincome countries, patients over 60 years of age receive 75% of all transfusions. Transfusion rates in patients below 15 years of age vary between 4 and 8% of all transfusions in the French and New Zealand Hemovigilance reports, respectively. Thus, transfusion in children, infants, neonates, and preterm babies outside specialized hospitals, although not rare, remains somewhat arcane even for transfusion medicine specialists. The rate and severity of transfusion-associated adverse events in pediatric population is difficult to ascertain, as few hemovigilance reports analyze findings by age. The SHOT 2019 report stated that children were usually overrepresented as percentages of total reports, particularly in cases of underand overtransfusion (31.4%). The French Hemovigilance Report found that the highest rate of notification takes place at 10–14 years of age, probably due to inferior notification in adults. The New Zealand report 2019 recorded a 7% adverse event notification rate below 15 years of age. However, none of these hemovigilance systems included hyperkalemia among reportable adverse events, and only the French report included some cases of “metabolic alterations”. Hyperkalemia, or excess of potassium (K) in blood, is a well-recognized adverse effect of transfusion. Hyperkalemia is usually associated with pediatric transfusion; it is considered a transient effect of rapid blood infusion in adults. Fatal cardiac effects are the most feared consequences of hyperkalemia. The effects of hyperkalemia range from electrocardiographic changes (peaked T waves, loss of P-wave amplitude, prolonged PR interval, and QRS duration) to ventricular fibrillation or asystole, leading to mechanical arrest of the heart and death in the most severe cases. Vraets et al. in 2011 summarized the evidence surrounding transfusion-associated hyperkalemia (TAH): (1) the supernatant K concentration of RBCs increases linearly and is directly related to the duration of RBC storage; (2) stored RBC units may contain enough supernatant K to produce hyperkalemia if large volumes are transfused; (3) the rise in a patient's serum K level is usually transient due to redistribution of the K load; (4) available evidence suggests that transfusion-associated hyperkalemic cardiac arrest is a real phenomenon; and (5) there is a distinct lack of high-quality data on the incidence of hyperkalemia following transfusion. Cold storage of RBC units induces K leak from RBCs due to inhibition of the Na-K-ATPase pump by low temperatures. Irradiation of RBCs results in significant changes in some markers of RBC quality, most notably, increased hemolysis and K leakage. Therefore, K Received: 1 March 2021 Accepted: 1 March 2021