Familial pseudohyperkalemia induces significantly higher levels of extracellular potassium in early storage of red cell concentrates without affecting other standard measures of quality: A case control and allele frequency study

Abstract

Background Familial pseudohyperkalemia (FP) is characterized by an increased rate of potassium leakage in refrigerated red cells and is associated with the minor allele of the single nucleotide polymorphism rs148211042 (R723Q) in the ABCB6 gene. The study aims were to obtain the minor allele frequencies of ABCB6 variants and to measure supernatant potassium accumulation, and other red cell storage parameters, in red cell concentrates (RCC) from carriers of variant rs148211042 under standard blood bank conditions. Study Design Whole blood units were collected from 6 FP individuals and 11 controls and processed into RCC in additive solution. RCC were sampled and tested over cold storage for full blood count, extracellular potassium, glucose, lactate, microvesicle release, deformability, hemolysis, pH, adenosine triphosphate, and 2,3‐diphosphoglycerate. Results Screening of genotyped cohorts identified that variant rs148211042 is present in 1 in 394 British citizens of European ancestry. FP RCC had significantly higher supernatant potassium at all time points from day 3 onwards (p < .001) and higher mean cell volume (p = .032) than controls. The initial rate of potassium release was higher in FP RCC; supernatant potassium reached 46.0 (23.8–57.6) mmol/L (mean [range]) by day 5, increasing to 68.9 (58.8–73.7) mmol/L by day 35. Other quality parameters were not significantly different between FP RCC and controls. Conclusion These data suggest that if a blood donor has FP, reducing the RCC shelf‐life to 5 days may be insufficient to reduce the risk of hyperkalemia in clinical scenarios such as neonatal large volume transfusion.

Reticulocyte Maturation

“…To our knowledge, the degree of reticulocyte maturation in DHSt RBC has yet to be analyzed. It is not anticipated that FP RBCs will have a reticulocyte maturation defect as FP is a benign, asymptomatic condition [ 132 ]. Together the study of reticulocyte maturation in HSt variant RBCs provided an insight into the reticulocyte maturation process and a better understanding of the effect of HSt variants on RBC maturation.…”

Case Report: Familial Pseudohyperkalemia Due to Red Blood Cell Membrane Leak in a Chinese Patient

“…Unfortunately, we were not able to conduct a thorough survey of her pedigree; The heterozygous R723Q SNP (rs148211042) was reported as present in approximately 1: 500 UK donors and the R375W SNP (rs764893806) is thought to be present in approximately 1:35,000 UK donors; the variant R276W was present in 0.3% (1/327) of blood donors from South Italy ( 21 ). The estimated accumulative frequencies of FP individuals are 1/785 in Asian population ( 22 ). Since few FP cases have been reported in Asia, FP prevalence might be substantially understated.…”

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

“…Two healthy controls were sex‐ and age‐matched to each FP individual. The five FP individuals participating in this study were different from our previous study of FP RBC 9 …”

“…The minor allele frequency of this variant in Britons with European ancestry was found to be 1 in 788 from screening different genotyped population cohorts. As this is a dominantly inherited condition, this results in 1:394 individuals in the British population with FP 9 . The rise in supernatant potassium concentration over cold blood storage of RBC from carriers of variant rs148211042 has been previously studied within our group 9 .…”

“…As this is a dominantly inherited condition, this results in 1:394 individuals in the British population with FP 9 . The rise in supernatant potassium concentration over cold blood storage of RBC from carriers of variant rs148211042 has been previously studied within our group 9 . That study showed that the supernatant in FP red cell concentrates (RCC) contains significantly higher potassium levels than control RCC (non‐FP) as early as Day 3 of cold storage, which reach near maximal levels by Day 5.…”