Irradiated red blood cells: Can all sins be washed away?

We read with interest the study on transfusion-associated hyperkalemia (TAH) by Yamada et al.¹ and the editorial by Romon and Cortes.² We thank the authors for their letter to increase awareness of TAH. We completely agree that indication for use of irradiated red blood cell (RBC) units needs to be refined and use of other measures like potassium filters and washing of units prior to transfusion should be tailored according to clinical settings.

A particularly high-risk patient cohort is the neonates and infants undergoing cardiac surgical repair using cardiopulmonary bypass (CPB). Despite major improvements in CPB, the patient blood volume:priming volume with homologous blood remains as high as 1:1. Prior studies have demonstrated significant hyperkalemia in these patients especially in those ≤5 kg.³ Despite the benefits of using fresh whole blood for CPB prime,⁴ it is not widely used and the use of fresh RBCs vs irradiated RBCs vs irradiated washed RBCs needs further investigation. Mitigation strategies such as ultrafiltration and cell washing have also not been systematically evaluated.

Washing of units can effectively reduce potassium and lactate levels. In our experience of analyzing blood units before and after washing we observed a significant reduction in the potassium (pre vs. post: 14.3 [14.3–14.3] vs. 1.3 [1–1.5] mmol/L; p = .001) and lactate levels (pre vs. post: 9.3 [4.65–11.45] vs. 4 [2.1–5.6] mmol/L; p = .001) with washing as seen previously. Other notable changes with washing are a rise in sodium (pre vs. post: 128.55 ± 5.35 vs. 143.91 ± 1.64; p < .001) and a fall in glucose (pre vs. post: 496 [360–683] vs. 52 [36.5–95.5] mg/dl; p = .0001) (Table 1). While we have not noticed clinical hypernatremia, early in our experience after instituting cell washing clinical hypoglycemia was noted in at least 2/20 patients, leading to more aggressive glucose monitoring and replacement. This contrasts with a previous study in which washed RBCs via an autotransfusion device induced hyperglycemia in patients after transfusion.⁵ What is even more significant is that these high potassium and lactate levels were seen in relatively fresh (≤4 days old) units that were irradiated on the morning of the surgery (≤6 h prior to use). While time related data on the effect of storage lesions on units with irradiation is limited, it is well known that metabolic derangement worsens with age of units and with increasing time interval since irradiation. However, the alarming degree of metabolic derangement seen with these units with such a short shelf-time and such short interval since irradiation urges us to reevaluate the need for fresh non-irradiated blood for neonatal and infant cardiac surgery.⁴

TABLE 1.

Cell saver data: Pre and post washing of packed RBCs

	Pre-washing (mean ± SD) N = 10	Post-washing (mean ± SD) N = 10	p value
pH	6.83 ± 0.08	6.79 ± 0.04	.11
Hct%	65.66 ± 4.65	63.52 ± 5.91	.27
K+, mmol/L	14.3 (14.3–14.3)	1.3 (1–1.5)	.001*
Na+, mmol/L	128.55 ± 5.35	143.91 ± 1.64	<.001*
Glucose, mg/dl	496 (360–683)	52 (36.5–95.5)	.001*
Lactate, mmol/L	9.3 (4.65–11.45)	4 (2.1–5.6)	<.001*
HCO3−, mmol/L	9.59 ± 3.68	1.14 ± 0.24	<.001*

Note: Data presented as mean ± SD for parametric and median (IQR) for non-parametric distribution.

Pre and post wash levels of variables compared using paired t-test for parametric and Wilcoxon signed-rank test for nonparametric variables.

^*Statistically significant difference between pre- and post-washing samples.

Washing of RBCs does not come without risks and additional hurdles that must be considered. The American Association of Blood Banks, the Council of Europe, and the Canadian Standards Association all state that washed RBCs must be used within 24 h due to the risk of bacterial contamination, and concerns for the deterioration of various transfusion component quality. Washing of RBCs can also increase the amount of plasma free hemoglobin, prolongs CPB setup time, and is labor-intensive especially during the post CPB resuscitation phase.

The intervention of RBC washing can also mitigate the deleterious inflammatory response after CPB, pointing toward the role of many hitherto unmeasured factors produced during RBC storage and irradiation that can contribute to morbidity and mortality in infants undergoing open heart surgery. Can RBC washing, and other mitigating measures effectively counter the added severity of storage lesions from irradiation of RBC units for our most vulnerable patients (neonates and infants requiring CPB)? The best and only way to get clear answers to these questions would be for the pediatric community to collectively study these issues and factors in a prospective randomized controlled trial of fresh whole blood vs. banked irradiated blood use for neonatal and infant CPB.

Pooled data was collected from 10 units of irradiated RBCs processed with Cell Savers (XTRA [LivaNova, London, UK] or Fresenius Kabi C.A.T.S plus [Terumo Cardiovascular, Ann Arbor MI]) prior to CPB prime. All units were 4–5 days old, irradiated on the morning of surgery (<3 h prior to use). After verification of units, donor RBCs were added to the cell saver reservoir using a 200-μm blood filter. Additional 500 ml of 0.9% Sodium Chloride was added. Units were used for priming the CPB circuit after processing. Blood gas analysis was performed using epoc Blood Analysis System (Siemens Medical Solutions USA, Inc. Malvern, PA).

This is a project undertaken as a Quality Improvement Initiative at Children's National and it does not constitute human subjects research. As such it was not under the oversight of the Institutional Review Board.