Falsely elevated serum salicylate concentration secondary to hyperlipidemia

Dear Editor,

We report a case of falsely elevated salicylate concentration similar to the case reported by Biary et al. [1] published earlier this year.

A 46-year-old male presented to the emergency department following a work related motor vehicle crash causing minor injuries and lacerations needing sutures. The patient’s medical history includes type 2 diabetes, hyperlipidemia, peripheral neuropathy, gout, and GERD. His medications include allopurinol, atorvastatin, canagliflozin, gabapentin, gemfibrozil, glimepiride, lisinopril/hydrochlorothiazide, metformin, omeprazole, propranolol, and an investigational drug made from hepatocyte growth factors (not thought to interact with salicylate assay). The patient requested toxicology testing to document he was not impaired at the time of the crash.

The serum and urine drug screens were negative except the salicylate concentration that resulted >100 mg/dL (ref. 15–30 mg/dL), triggering further labs and workup for salicylate intoxication. The patient denied taking any source of salicylates and was asymptomatic outside of his physical injuries sustained in the crash. The patient was held for observation while the elevated salicylate lab was investigated, but was not alkalinized or dialyzed since the clinical appearance did not indicate a genuine toxicity. A venous blood gas returned pH 7.41 (ref. 7.31–7.41), pCO₂ 37 mmHg (ref. 40–50), and HCO₃ 23 mmol/L (ref. 23–29). The hospital lab repeated the salicylate concentration four times, all resulting with salicylate concentration >100 mg/dL. Further investigation identified hyperlipidemia as a potential source of interference with spectrophotometric quantification. The patient’s lipids were: total cholesterol 200 mg/dL (ref. 120–200 mg/dL), triglycerides 1888 mg/dL (ref. 40–150 mg/dL), HDL 17 mg/dL (ref. 40–60 mg/dL), LDL 14 md/dL (ref. 0–13 mg/dL). To address hyperlipidemia the lab treated the patient’s serum with a lipoprotein removal reagent (LipoClear^® Beckman Coulter, Brea, CA) and the salicylate concentration resulted <5 mg/dL. Following the negative salicylate concentration the patient discharged home after a night admitted to the hospital.

The available literature discussing the effect of hyperlipidemia on spectrophotometric analysis is contradictory. When the salicylate hydroxylase method became available it was thought that lipemia would not have any effect on the assay, but one paper does not state the degree of lipemia tested [2]. The hospital lab policy in this case explicitly stated that lipemia has no significant interference on the salicylate assay. Subsequent publications state various spectrophotometric assays are affected by hyperlipidemia because lipoproteins can scatter light, changing the absorbance spectra [3–6]. Another study has shown that increasing lipid concentrations resulted in falsely high salicylate concentrations, and different analyzers can produce different results even with the same degree of lipemia [5].

At the time of this writing two other published cases of hyperlipidemia caused false salicylate concentration exist (see Table 1) [1, 7]. However, there is no clear information available regarding the clinical relevance that hyperlipidemia has on salicylate concentrations. This case shows that a triglyceride concentration more than 3 fold lower than previously demonstrated will cause this lab error, on a Seimens Advia 1800 analyzer.

Table 1. Known cases of false salicylate concentrations.

	Case 1	Case 2	Current case
Triglyceride (mg/dL)	6390	7650	1888
Salicylate (mg/dL)	77–109	>100	>100
Equipment	Unknown	Siemens	Siemens Advia 1800
Method	Enzymatic/Spectrophotometric	Colorimetric*	Enzymatic/Spectrophotometric
Salicylate after clearing lipids	Undetectable	Undetectable	Undetectable

* Unable to verify, likely salicylate hydroxylase method as well

If not recognized, hyperlipidemia can produce alarmingly elevated serum salicylate concentrations, which may lead to unnecessary use of healthcare resources.