Study summary
The ‘CARED’ study investigates rare genetic variants in red blood cells which cause a condition known as familial pseudohyperkalaemia (FP). Pseudohyperkalaemia means ‘falsely elevated potassium in blood’. In FP, red cells behave normally at body temperature but not at cold temperatures; thus, FP is not known to affect an individual’s wellbeing and it is usually undetected.
Red cells from donated blood are stored in special storage bags in the fridge for up to 35 days prior to transfusion. During this time potassium slowly leaks out of the red cells into the surrounding liquid in the storage bag. FP red cells release high levels of potassium much more quickly than red cells without FP (standard) at cold temperatures.
Due to the help from the Bioresource volunteers, who donated their blood for this study, the research team were able to show that red cells from individuals with FP, have similar potassium levels in the bag on day 7 of cold storage to standard red cells on day 35.
In the blood service, the Blood Service now restrict the shelf life of red cells meant for transfusing babies or small children at large amounts from 35 to only 5 days after the blood has been collected; in part to control for the amount of potassium in the bag of red cells. This is because transfusion of large amounts of potassium could have negative consequences for vulnerable recipient groups. As FP red cells would have unexpectedly high levels of potassium early in storage, the risk is too high for the infant population. Therefore, due to this study, red cell donations from known FP individuals are prevented from being transfused to babies or small children. However, red cell donations from FP individuals are still acceptable for transfusion to adult recipients.
In a follow up study, the research team wanted to see what effect irradiation has on FP red cells. Irradiating red cells is a standard procedure for recipients with low immune system, as it ensures any white cells left over in the red cell bag, which could harm the recipient, are rendered inactive. Irradiation causes some damage to the red cells, including increased release of potassium, so the team wanted to determine whether this damage is worse in FP red cells.
In a study conducted across 2 centres, in Cambridge and in Australia, blood was collected from Bioresource volunteers, as well as from Australian Red Cross Lifeblood from donors in Australia. The team found that irradiating FP red cells did not cause worse damage, and the red cells have acceptable quality for transfusion. This is an important finding that reassures our patients’ safety.
The CARED group would like to thank Bioresource volunteers for their donation that made these studies feasible.
Study Findings:
The findings from this study have been published in The Journal of AABB Transfusion in 2022. See here for further details.
Study Update (August 2026):
The ‘CARED’ study investigates rare genetic changes in red blood cells which cause a condition known as familial pseudohyperkalaemia (FP). Pseudohyperkalaemia means ‘falsely elevated potassium in blood’. All red cells naturally lose potassium over time but at normal body temperature they continuously restore it to keep the right balance. In FP, red cells behave normally at body temperature, however at cold temperatures they release potassium more quickly than red cells without FP. We found this in a previous CARED study. FP is not known to affect an individual’s wellbeing and it is usually undetected.
Donated red cells are stored in a solution called ‘additive solution’, that provides them with nutrients like glucose and adenine to function over cold storage prior to transfusion. Over cold storage, red cell metabolites, proteins and potassium cations accumulate in the additive solution. FP red cells accumulate larger amounts of potassium earlier in storage than standard red cells. Transfusion of large amounts of potassium could have negative consequences for vulnerable recipient groups and the potential risk may be too high for infants receiving transfusions. Therefore, we prevent red cell donations from known FP individuals from being transfused to babies or small children. However, red cell donations from FP individuals are still acceptable for transfusion to adult recipients.
Some recipients can be allergic to plasma proteins that may be carried over into the red cell additive solution during the manufacturing process. For those recipients, or recipients/procedures that are more vulnerable to high levels of potassium, the red cells are specifically ‘washed’. This means the additive solution is removed (within 14 days of cold storage) and replaced with fresh solution which is depleted from plasma proteins and potassium.
In this study, we investigated what happens to the function of the red cells with FP, which have lost a lot of their potassium early in storage and this was then removed from the solution by washing. Our results show that washing red cells with FP does not damage the red cell membrane or affect the red cell function, the red cells continue to release the potassium left in their intracellular stores allowing potassium levels to reach a balance between inside and outside the cell. If the wash takes place early in storage, as soon as a day after the wash the FP red cells will have released higher potassium levels in the additive solution compared to standard red cells. However, in standard practice, the red cells are transfused on the same day after the washing process, and this does not pose an increased risk to the recipient if the red cells are FP. This is an important finding that reassures our patients’ safety.
On behalf of the CARED group we would like to take this opportunity to thank you for your donation that made this study possible.
Best wishes,
The CARED group
Study Findings:
Further findings from this study have been published in The Journal of AABB Transfusion in 2026. See here for further details.