Familial pseudohyperkalemia (FP) is an underrecognized cause of pseudohyperkalemia, caused by the leaking of potassium from red blood cells. This extracellular shift of potassium is temperature-dependent and occurs when blood samples are stored below room temperature or for a long time, manifesting as apparent hyperkalemia. We report a suspicious case of FP, which demonstrated an apparent seasonal trajectory of serum-potassium levels at the local clinic. At first, laboratory test results did not show an increase in the serum-potassium levels in our tertiary hospital. However, by replicating the clinic's storage conditions, the patient's serum sample showed hyperkalemia only when it was stored at a temperature of 4 °C or 20 °C for 4-8 h. Hyperkalemia was not observed in the patient's sample when it was stored at 37 °C, or in the healthy control's sample at a temperature of 20 °C or 37 °C. When encountering hyperkalemia without an obvious cause and symptoms, physicians should consider pseudohyperkalemia in the differential diagnosis. In particular, if a seasonal trajectory of serum-potassium levels is observed, FP should be suspected as a potential cause of pseudohyperkalemia. Although a genetic test is needed to properly diagnose FP, confirming it by verifying the sample storage conditions or proving it by replicating the test using different storage conditions is easy and very important, as it can prevent unnecessary treatment.

We herein report two suspected cases of pseudohyperkalemia who presented with severe hyperkalemia examined at small primary care clinics; however, re-exams at a tertiary care hospital showed normal potassium levels. We reproduced the laboratory examination conditions of the clinics and found that hyperkalemia was due to sampling/storage condition of serum, which is strongly suggestive of familial pseudohyperkalemia (FP). FP is a possible but under-appreciated cause of hyperkalemia, which does not require treatment, so it is important to include FP in the differential diagnosis of hyperkalemia especially in cases with discrepant of serum potassium levels at different settings.

Study and management of a case with elevated potassium levels without apparent clinical causes in successive follow-up visits. We present the case of a primary care female patient who persistently exhibited elevated levels of potassium (5.3-5.9 mmol/L) in successive control laboratory tests, without an apparent clinical cause. The patient was ultimately referred to the Unit of Nephrology, where a potassium-low diet was indicated. Diet did not have any effect on potassium levels. After a thorough study, the cause of hyperkalemia could not be determined. The inconsistency between elevated potassium levels and the reason of consultation, and exclusion of other pre-analytical or pathological causes raised suspicion of familial pseudohyperkalemia. The sample was incubated at different times and temperatures to demonstrate their influence on levels of potassium in blood. Familial pseudohyperkalemia was established as the most probable diagnosis. Finally, the patient was discharged from the Unit of Nephrology and instructed to follow a normal diet.

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. 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. 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. FP does not increase the rate of potassium leak from irradiated RBCs. Irradiation may cause a membrane defect similar to that in FP RBCs.

Hyperkalemia is an electrolyte disorder requiring medical attention because it can cause cardiac arrhythmias. Pseudohyperkalemia is the phenomenon of an elevated potassium concentration that is present in the blood sample but not in the patient. Pseudohyperkalemia can be caused by hemolysis, leukocytosis, thrombocytosis, seasonal pseudohyperkalemia, potassium release from muscle cells due to fist clenching during venipuncture, and contamination due to blood withdrawal from an intravenous line over which potassium was administered. Rarer causes include EDTA contamination and familial pseudohyperkalemia. A 23-year old woman was admitted with ascites due to polycythemia vera and essential thrombocytosis for which hydroxycarbamide was started. The reported serum potassium concentrations were 6.1 and 6.8 mmol/l. The use of spironolactone was discontinued and she was treated with sodium polystyrene sulfonate and insulin-glucose infusion. The serum potassium concentration only decreased on the ninth day of admission, when the thrombocyte count was normalizing. A diagnosis of pseudohyperkalemia due to thrombocytosis was established. Knowledge of the causes of pseudohyperkalemia and interaction between the clinician and clinical chemist aids in the differentiation between true hyperkalemia and pseudohyperkalemia and may prevent unnecessary diagnostics and harmful treatment.