The compound effect of irradiation and familial pseudohyperkalemia on potassium leak from red blood cells

Abstract

Background Familial pseudohyperkalemia (FP) is a rare asymptomatic condition characterized by an increased rate of potassium leak from red blood cells (RBC) on refrigeration. Gamma irradiation compromises RBC membrane integrity and accelerates potassium leakage. Here, we compared the effect of irradiation, applied early or late in storage, on FP versus non‐FP RBC. Study Design Five FP and 10 non‐FP individuals from the National Institute for Health Research Cambridge BioResource, UK, and three FP and six non‐FP individuals identified by Australian Red Cross Lifeblood consented to the study. Blood was collected according to standard practice in each center, held overnight at 18–24°C, leucocyte‐depleted, and processed into red cell concentrates (RCC) in Saline Adenine Glucose Mannitol. On Day 1, RCC were split equally into six Red Cell Splits (RCS). Two RCS remained non‐irradiated, two were irradiated on Day 1 and two were irradiated on Day 14. RBCs were tested over cold storage for quality parameters. Results As expected, non‐irradiated FP RCS had significantly higher supernatant potassium levels than controls throughout 28 days of storage (p < .001). When irradiated early, FP RCS released potassium at similar rates to control. When irradiated late, FP RCS supernatants had higher initial post‐irradiation potassium concentration than controls but were similar to controls by the end of storage (14 days post‐irradiation). No other parameters studied showed a significant difference between FP and control. Discussion FP does not increase the rate of potassium leak from irradiated RBCs. Irradiation may cause a membrane defect similar to that in FP RBCs.

Vesiculation in irradiated and cation‐leaky‐stored red blood cells

“…23,[35][36][37] It is also of interest because we have recently shown that irradiated RBCs have a very similar cation leak profile to FP RBCs. 14 Now, we show that cation-leaky RBCs (whether FP or irradiated) have very similar vesiculation profiles to each other and to control non-FP RBCs during cold-storage. It has been known for many years that irradiation increases the RBC plasma membrane permeability to cations 10 ; however, the membrane defect causing this permeability has not been determined.…”

“…As reported previously, 14 haemolysis was measured in the SN fraction, at all time-points +/À irradiation. Haemolysis increased with storage time but did not appear to be affected by irradiation (Supplemental Figure 2).…”

“…13 We have recently shown that the rate of potassium leak from RBCs during hypothermic storage post-irradiation (day 1) is very similar to that of FP RBCs with or without irradiation. 14 Comparison of other RBCs parameters, such as metabolic measurements, deformability and haemolysis, showed no significant difference between irradiated and non-irradiated RBCs. 14 Vesicles in stored blood have been associated with adverse transfusion outcomes, including increased inflammatory responses, pro-coagulant activity, neutrophil activation, and nitric oxide scavenging.…”

“…14 Comparison of other RBCs parameters, such as metabolic measurements, deformability and haemolysis, showed no significant difference between irradiated and non-irradiated RBCs. 14 Vesicles in stored blood have been associated with adverse transfusion outcomes, including increased inflammatory responses, pro-coagulant activity, neutrophil activation, and nitric oxide scavenging. [15][16][17][18][19][20][21][22][23] We thought it important to determine whether factors that affect the permeability of the RBC membrane, such as irradiation and/or FP, also affect the production of vesicles during hypothermic storage.…”

“…We have recently shown that the rate of potassium leak from RBCs during hypothermic storage post‐irradiation (day 1) is very similar to that of FP RBCs with or without irradiation 14 . Comparison of other RBCs parameters, such as metabolic measurements, deformability and haemolysis, showed no significant difference between irradiated and non‐irradiated RBCs 14 …”