When raised potassium may be a false flag – pseudohyperkalaemia unmasking thrombocytosis

Under the radar: GP Dr Chitra Nair describes how pseudohyperkalaemia can occur with raised platelets and how in one case this helped to unmask essential thrombocytosis

Note details of the case in this article have been altered to ensure anonymity

The case

Routine NHS health check blood tests in a 45-year-old female showed a potassium of 6.3 with a normal eGFR, normal HbA1C and normal lipid profile.

There was no significant past medical history or comorbidity on the patient’s record, and no regular medication.

On checking the trend, it was noticed that U&Es were last done 3 years ago when the patient had bloods done for a routine pre-operative work-up for nasal polypectomy. Her potassium then was 6.7, so the pre-op nurse had sent her to A&E. The repeat potassium was normal and the patient therefore sent home. However, a FBC done at that point had shown that, while all other parameters were normal, she had a slightly raised platelet count of 515 x 10⁹.

Her GP immediately followed up by telephone; the patient reported being completely asymptomatic. An ECG and urgent bloods were organized the next day with a face-to-face patient review.

The ECG was normal and repeat potassium 5.0, but the platelet count was 635 x 10⁹. Systems review and examination were normal. Given the thrombocytosis, a FBC was repeated 6 weeks later with a full thrombocytosis screen (ferritin, iron studies, inflammatory markers, chest X-ray, FIT test, autoantibody screen). The repeat tests were all normal but platelet count was persistently raised, at 630 x 10⁹.

Diagnosis and outcome

The patient was referred to Haematology. She had further testing done including genetic testing for JAK2 mutation and bone marrow biopsy. The patient was diagnosed with essential thrombocytosis and was started on hydroxycarbamide and aspirin. She is now doing well and her platelet counts have normalized.

Recognising pseudohyperkalaemia and what causes it

Pseudohyperkalaemia is falsely raised potassium where the reported potassium result is higher than the patient’s actual physiological potassium level. It is an in vitro phenomenon whereby potassium leaks out of blood cells after the sample is taken, during handling or testing. Patients can be asymptomatic and have no ECG changes. If erroneously treated it can lead to iatrogenic hypokalaemia.

Most common causes relate to issues with collection, storage and transporting samples. This might for example be due to difficult phlebotomy or overheating, cooling or prolonged storage of the sample.

Raised counts – be that erythrocytes, leucocytes or platelets – increase the amount of intracellular potassium available to leak into the specimen after collection leading to pseudohyperkalaemia.

Repeating the test and sending it for analysis within 3 hours of collection is essential to differentiate it from true hyperkalaemia. Ideally a paired serum (clotted tube) and plasma potassium (unclotted in lithium heparin tube) should be requested. If the serum potassium is more than 0.4 mmol/L higher than the plasma potassium, it suggests pseudohyperkalaemia rather than true hyperkalaemia.

In patients with thrombocytosis, there is increased release of potassium from the activated platelets during the process of clotting in standard serum separating tubes used for blood collection. In isolated thrombocytosis repeating the counts and looking at secondary causes – for example, iron deficiency, infection, inflammation or malignancy, is essential. Persistent, unexplained thrombocytosis then needs to be referred to haematology for further investigations and treatment to avoid thrombotic complications.

Key learning points for GPs

True hyperkalaemia is rare in patients without renal impairment.
Pseudohyperkalaemia, where patients are asymptomatic and have normal physiological potassium but elevated potassium on blood testing, should always be considered in patients with unexplained hyperkalaemia.
It is caused by problems with blood sample collection/handling which lead to potassium leaking from blood cells into the serum.
Pseudohyperkalaemia can be exacerbated by raised blood platelets, erythrocytes or leucocytes which increase the amount of intracellular potassium available to leak into the sample.
An unexplained elevated potassium should be repeated; samples should be sent for analysis within 3 hours of collection and ideally a paired serum and plasma potassium should be requested – a serum potassium > 0.4 mmol/L above the plasma potassium suggests pseudohyperkalaemia rather than true hyperkalaemia.
In this case a simple NHS heath check and raised potassium unmasked the true underlying pathology essential thrombocytosis.