Pseudohyperkalaemia or spurious hyperkalaemia

In this article I discuss pseudohyperkalaemia, particularly as reflected in the pages of the Annals of Clinical Biochemistry. In the last decade or so a series of papers have been published in this journal that have helped clarify this situation and aided its recognition and management. Pseudohyperkalaemia can be defined as an elevation in serum/plasma potassium concentration that occurs either due to transcellular movement of potassium ions out of cells, during or after phlebotomy, or is the result of contamination of blood samples with potassium containing substances. It does not necessarily reflect true hyperkalaemia; indeed there are usually no related electrocardiographic changes or symptoms of hyperkalaemia. In addition, hypo-kalaemia can also be ‘masked’ as normokalaemia in such circumstances. ¹ Interestingly, an autosomal dominant familial form of pseudohyperkalaemia has recently been discovered. The responsible gene, ABCB6 located on the long arm of chromosome 2 (2q36), causes a defect of the erythrocyte membrane. ²

Pseudohyperkalaemia was probably first described about 50 years ago by Hartmann et al. ³ in a patient with thrombocytosis and this was also subsequently reported in patients with erythrocytosis and leukocytosis. In these cases intra-cellular potassium ions are released as a result of the coagulation process in the blood sample.

In 1997 Kilpatrick and Burton ⁴ reported in the Annals a case of pseudohyperkalaemia in a patient with hereditary spherocytosis. More recently, Lukens et al. ⁵ described pseudohyperkalaemia in a patient with ‘leaky’ cell syndrome. In this case cooling blood down to ambient temperature after venepuncture diminished Na⁺/K⁺ ATPase pump activity thus enhancing potassium leakage. Seasonal pseudohyperkalaemia has also been reported due to delayed centrifugation of blood samples, particularly with certain gel separators. The phenomenon is more common in colder weather which enhances the ‘leakage’ of potassium ions from cells.^6,7 Turner et al. ⁸ introduced centrifuges into all general practices in the NHS Grampian region in Scotland which significantly reduced the occurrence of pseudohyperkalemia and also of seasonal variation in mean serum potassium concentration; thereby improving the overall quality of their potassium results. ⁸

Phlebotomy technique is also important including avoiding flexing/clenching of fingers and hands during the procedure to reduce pseudohyperkalaemia. ⁹ Bailey and Turlow ¹⁰ reduced the occurrence of pseudohyperkalaemia by training phlebotomists to avoid requesting patients to hand grip (fist clench) during phlebotomy and they also suggested that this cause of pseudohyperkalaemia has been underestimated in clinical practice.

Hira et al. ¹¹ reported that recentrifugation of blood samples after storage causes a clinically significant increase in pseudohyperkalaemia. They also went on to show that although about half the laboratories had asked their collection facilities to centrifuge blood samples on site, very few complied. Pseudohyperkalaemia appeared to be a relatively common problem in commercial laboratories in Japan, in part due to prolonged times before centrifugation and it was proposed that improved handling at blood collection sites and in laboratories could avoid this problem. ¹²

Contamination is also a significant cause of pseudo-hyperkalaemia. Cornes et al. ¹³ highlighted the significance of potassium ethylenediaminetetraacetic acid (K-EDTA) contamination of laboratory blood samples as a problem. K-EDTA contamination can result in potentially dangerous spurious laboratory results including hyperkalaemia but also hypocalcaemia, hypomagnesaemia and hypozincaemia. It is essential that while collecting serial blood samples and when different blood tubes are attached to the indwelling phlebotomy needle, that the non-EDTA anticoagulated samples are taken first while the K-EDTA tubes should be taken last. ¹⁴ Additionally, blood should not be decanted from K-EDTA tubes to other blood collection tubes. Davidson ¹⁵ has described an assay for measuring EDTA so as to facilitate detection of contaminated samples.

In summary, pseudohyperkalaemia occurs when the in vitro serum/plasma potassium concentration is spuriously elevated while the in vivo plasma potassium concentration is not. The most frequent causes are blood cell or coagulation abnormalities, delayed time from sampling to centrifugation and phlebotomy technique. A paired plasma and serum sample and full blood count can help determine the cause of pseudohyperkalaemia in many cases. ¹⁶ The series of papers in the Annals of Clinical Biochemistry alluded to in this article describing pseudohyperkalaemia illustrate to my mind one of the strengths of the Journal; namely the provision of practical, clinically relevant and educational articles that help improve analysis of patient samples and ultimately optimize patient care. As we move towards larger, more geographically dispersed laboratories, I suspect that pseudohyperkalaemia will remain an issue we will all have to address.

Declarations

Competing interests: None.

Funding: None.

Ethical approval: N/A.

Guarantor: MAC.

Contributorship: MAC is the sole author.

Acknowledgements: None.