Clinical Conundrum
Did you know Heparin can cause hyperkalemia? What is the proposed mechanism…& what is the onset?
Background
Heparin is a heterogenous mixture of sulfated polysaccharide polymers that is frequently used for treatment and prophylaxis of VTE.
The most common adverse effects of heparin are hemorrhage, thrombocytopenia, HIT and HITT, hypersensitivity reactions, and elevations of aminotransferase levels.
Heparin induced hyperkalemia has been observed in 7% of patients treated with unfractionated heparin. It is also observed in low molecular weight heparin (LMWH), although its occurrence is rare.
Answer
The proposed mechanism of heparin induced hyperkalemia is aldosterone inhibition by reduction in number and affinity of the aldosterone receptors in the zona glomerulosa.
Aldosterone suppression and increase in potassium occurs within a few days of heparin initiation, as soon as 1-3 days and maximally by 3-5 days.
Most patients are able to compensate for hypoaldosteronism, but some risk factors that may predispose patients for heparin induce hypoaldosteronism include diabetes, renal insufficiency, type 4 renal tubular acidosis, and metabolic acidosis.
Although, there have been a few reports of severe hyperkalemia, typically there is no life threatening or symptomatic hyperkalemia and potassium levels will return to normal upon discontinuation of heparin and LWHH.
References
1. Oster JR, Singer I, Fishman LM. Heparin-induced aldosterone suppression and hyperkalemia. Am J Med. 1995;98(6):575-586. doi:10.1016/s0002-9343(99)80017-5.
2. Orlando MP, Dillon ME, O'Dell MW. Heparin-induced hyperkalemia confirmed by drug rechallenge. Am J Phys Med Rehabil. 2000;79(1):93-96. doi:10.1097/00002060-200001000-00019.
3. Heparin [package insert]. New York, NY: Pfizer Labs; 2013.
4. Koren-Michowitz, Maya. “Early Onset of Hyperkalemia in Patients Treated with Low Molecular Weight Heparin: a Prospective Study.” Pharmacoepidemiology and Drug Safety, vol. 13, no. 5, John Wiley & Sons,, 2004, pp. 299–302, doi:10.1002/pds.881.
5. Montague BT, Ouellette JR, Buller GK. Retrospective review of the frequency of ECG changes in hyperkalemia. Clin J Am Soc Nephrol. 2008;3(2):324-330. doi:10.2215/CJN.04611007.
Written by:
Justyna Fydrych, PharmD, PGY 1 Pharmacy Resident
Reviewed By: Joanne C. Routsolias, PharmD, RN, BCPS
Clinical PharmD Specialist - Emergency Medicine/ToxicologyReviewed By:
Joanne C. Routsolias, PharmD, RN, BCPS
Clinical PharmD Specialist - Emergency Medicine/Toxicology