Neonatal Transfusion with Red Blood Cells Stored in Additive Solution

by Dr Debra Smith

Storage of red blood cells (RBCs) in adenine-saline (AS) additive solutions extends shelf-life of the RBC unit from 21 days to 42 days. An RBC unit stored in AS solution is prepared by removing most of the plasma from a whole blood unit collected with citrate phosphate dextrose (CPD) or citrate phosphate double dextrose (CP2D) anticoagulant and adding 100 mL of AS solution. Alternatively, a CPDA-1 RBC unit (35-day shelf-life) can be prepared by plasma removal from a whole blood unit collected in citrate phosphate dextrose adenine (CPDA-1).

Available AS solutions differ in concentration of dextrose, sodium chloride, and adenine and presence or absence of mannitol, trisodium citrate, citric acid, and monobasic sodium phosphate. Anticoagulant and additive solution formulations are listed in the Table below. Concerns about the use of AS units in neonates arise from the higher concentrations of additives transfused. Mannitol, present in some AS formulations, raises concern for renal toxicity and possible fluctuations in cerebral blood flow. The possibility of renal toxicity is also related to higher adenine concentrations.¹

Evidence from clinical studies supports the safety of AS RBCs for small volume (<20 mL/kg) neonatal transfusions, and utilization of AS units for small volume neonatal transfusions is the standard practice for the majority of US institutions.² Randomized controlled studies have evaluated the safety of small volume neonatal transfusions of RBCs stored in AS-1 or AS-3 up to 42 days compared to CPDA RBCs stored up to 7 days.³ ⁴ In these studies, no clinical transfusion reactions were observed with AS transfusions, and only minimal changes in levels of glucose, lactate, pH, calcium, sodium, and potassium were seen. Additional studies support clinical safety of small volume neonatal transfusions with dedicated AS RBC units.⁵ ⁶

Evidence is less clear for use of AS RBCs for large volume (≥20mL/kg) neonatal transfusions, such as for exchange transfusion, general surgery, or cardiac bypass/extracorporeal membrane oxygenation (ECMO) prime. In a survey of neonatology units in the US, 72% of respondents used AS-1 or AS-3 units for large volume transfusion. In some cases, the transfusion order was accompanied by request for modification of the AS unit (washed or supernatant reduced) to reduce the amount of additive transfused.⁷

References:

1.       Luban NLC, Strauss RG, and Hume HA. Commentary on the safety of red cells preserved in extended-storage media for neonatal transfusions. Transfusion 1991;31: 229-235.

2.       Fung MK, Rozeff SD, and Overmuch KL. Blood component preferences of transfusion services supporting infant transfusions: a University HealthSystem Consortium benchmarking study. Transfusion. 2010;50: 1921-1925.

3.       Strauss RG, Burmeister LF, Johnson K, et al. AS-1 red blood cells for neonatal transfusions: a randomized trial assessing donor exposure and safety. Transfusion 1996; 36: 873-8.

4.       Strauss RG, Burmeister LF, Johnson K, et al. Feasibility and safety of AS-3 red blood cells for neonatal transfusions. J Perdita 2000; 136: 215-219.

5.       Mangel J, Goldman M, Garcia C, et al. Reduction of donor exposures in premature infants by the use of designated adenine-saline preserved split red blood cell packs. J Perinatal 2001; 21: 363-367.

6.       Van Straaten HL, de Wildt-Eggen J, Hoisted IA. Evaluation of a strategy to limit blood donor exposure in high risk premature newborns based on clinical estimation of transfusion need. J Perinat Med 2000; 28: 122-128.

7.       Pyles RB, Lowery JT, and Delaney M. The use of red cell units containing additives in large volume neonatal transfusion in neonatology units in the USA. ISBT Science Series. 2017; 12: 322–323.