Falsely decreased total cholesterol
| HOSP # | Req#452050196 | WARD | Pathcare Private |
| CONSULTANT | John Stanfliet / Jody Rusch | DOB/AGE | Unknown |
Abnormal Result
Presenting Complaint
This was a case discussed in consultation with a private consultant:
The patient was admitted with SARS-CoV-2.
History
The clinician was contacted regarding an extremely low LDL-cholesterol, not comparable with the other measurements.
Medication history was unknown at the time when these results became known and had to be authorized.
Examination
Not applicable and information not available.
Laboratory Investigations
| Test | Result |
| Lipaemia | Absent |
| Total Cholesterol | < 0.5 mmol/L |
| Triglyceride | 0.38 mmol/L |
| HDL Cholesterol | 1.9 mmol/L |
| Non-HDL-Cholesterol | -1.40 mmol/L |
| Cholesterol:HDL ratio | 0.3 |
| LDL-cholesterol (calculated) | Not done |
| LDL-cholesterol (measured) | 3.0 mmol/L |
| Glucose (fasting) | 5.0 mmol/L |
Other Investigations
From the results above it becomes clear that there are some discrepancies in the results. The total cholesterol, as measured on the Abbott Allinity (<0.5 mmol/L) does not compare against the measured LDL-cholesterol (3.0 mmol/L), which should be lower than the total cholesterol.
Other investigations to perform on this sample would perhaps be to run it on a different analyser.
Final Diagnosis
The clinician was phoned and it was found that the patient was on high doses of Vitamin C intravenously.
Take Home Message
When there’s a big discrepancy between LDL (measured – directly with a homogenous assay) and the total cholesterol, the cause should be determined, or at least investigated.
The Total cholesterol, LDL-cholesterol, Triglycerides and HDL-cholesterol all use Trinder reactions.
Vitamin C is a quencher in the reaction (likely due to its high anti-oxidant activity). Since COVID has been around, there are quite a lot of protocols of treatment with Vitamin C IV. It is likely that patients infused with IV N-acetylcysteine, also a potent anti-oxidant, will also cause spuriously low total cholesterol. Or perhaps spuriously low results in any reaction employing the trinder reaction.
It is also clear from this case how important it is to discuss results which do not make sense with clinicians.
Summary of the Trinder reaction
A few decades ago, Emerson presented a new color test reaction (Emerson 1943), which is still in common use for the determination of phenolic compounds (e.g. Ettinger et al. 1951; Fiamegos et al. 2002). Later, Trinder adapted this reaction for the determination of blood glucose using horseradish peroxidase (HRP), coupling the hydrogen peroxide produced from the glucose oxidase reaction, to the Emerson indicator reaction (Trinder 1969; Barham & Trinder 1972). For this reason, this reaction is also known as the Trinder reaction. The so-called Emerson–Trinder reaction, is now routinely used as a spectrophotometric indicator reaction in clinical chemistry, in which a quinoneimine dye product is produced by oxidative condensation of a phenol with 4-aminoantipyrine (4-AAP) (Emerson 1943). This indicator reaction was subsequently used for the spectrophotometric assay of a large number of substrates or enzymes (Burtis & Ashwood 1994) such as uric acid (Kabasakalian et al. 1973), cholesterol (Allain et al. 1974), free hemoglobin (Bauer 1981) or triglycerides (Fossati & Prencipe 1982) and also by using different organic hydrogen-donor compounds such as different substituted (ortho, meta and para) chloro or bromophenols, 4-hydroxybenzene-sulfonic acid (Wang et al. 1992), 2,4-dichlorophenol (Klose et al. 1978), 3,5-dichloro-2-hydroxybenzensulfonic acid (Fossati & Prencipe 1982; Fossati et al. 1980) or different aniline derivatives (Tamaoku et al. 1982).
Farzad Deyhimi, Massoud Arabieh & Lida Parvin (2006) Optimization of the Emerson–Trinder enzymatic reaction by response surface methodology, Biocatalysis and Biotransformation, 24:4, 263-271, DOI: 10.1080/10242420600661943