Variance of laboratory results

Dr Th Dhabali Singh MD *

It is often we come across discussions regarding laboratory tests results differing from one laboratory to another and then obtaining different tests results for the same person in the same laboratory. As simple as it is to point and say that the laboratory results are wrong, there is a lot more than meets the eye.

The very first thing everyone should be aware of is how a laboratory functions and how the tests results are interpreted and the factors on which the values are provided.The laboratory reports are notuniversal fit with a default one template for all individuals.

Why do reference ranges vary? : Routine blood tests have different reference ranges in different laboratories as the equipment are different and as such, the test methods also vary. We need to understand that there are factors that decide the variation of reference ranges. There is no universal reference range that we can rely on to establish a “normal range” for everyone.

The demographics of different populations such as Asians, Europeans, Americans etc., play a huge role in deciding the range for that particular population since we have different genetic structure and our lifestyles and food habits are different. What the diagnostic laboratories provide in the reports as normal range are the values expected of a normal healthy person of that particular population.

Again, these normal ranges are not specific ranges as the testing equipment and test methods will each have its calibrated reference range. For example, if we perform a random blood sugar in three methods – manual, semi-automatic and fully automatic analyzers, we will have three different detectable ranges and three different methods which will in turn provide 3 different readings of blood sugar for that same individual.

If a layman interprets the result, he or she will think that the result is wrong as all three results are different and will blame the laboratory as the individual does not understand why the variance is happening. The main reason why people think that the report of a certain laboratory is wrong is that they compare it with the results of another laboratory. However, it is also possible that the two laboratories might be using different equipment, chemical reagents and analysis techniques.

Reference ranges vs Decision limits : For few numbers of tests, long-term studies of certain diseases have led to the establishment of decision limits that are more useful than reference ranges in determining clinical interpretation and guiding treatment approaches.

Decision limits are values that represent either the upper or lower quantity of an analyte that are consistent with a disease state or indicate a need for treatment. For example, HbA1c (Glycated Haemoglobin test or Glycosylated Haemoglobin test) is a test to diagnose diabetes and also used for diabetic patients to test whether their average level of blood sugar are within range during the past 2 to 3 months.

As per High Performance Liquid Chromatography (HPLC) method, the decision limit to show a person as non-diabetic or pre-diabetic is value <6.5%.In this situation, it is a value above a particular limit that provides information rather than a value that falls within or outside a set range of numbers.

Diabetic Status HbA1c Levels
Non-Diabetic = Less than 5.7% (39 mmol/mol)
Prediabetic = 5.7% – 6.4% (39 – 46 mmol/mol)
Diabetic = 6.5% (47 mmol/mol) or greater
Well-controlled Diabetes = Less than 7.0% (52 mmol/mol)

Instrument calibration and quality control : Leading laboratories perform mandatory calibration of the instruments and run control tests every day before the patients samples are loaded for the specified tests. Calibrators give a reference point for the machine to adjust to.Controls (QC) make sure the machine is working properly. They are basically samples with known lab values.

If the results match what we expect, we know the machine is giving accurate results.If the QC is out of range, a calibrator can be used to adjust the machine so the QC results can be within the correct ranges. These two processes ensure that the equipment is giving results accurately within the defined reference range for a healthy individual. Precision of a result on the other hand doesn’t mean that the value sits in between the ranges.

Precision in this case is obtaining the same result with minimal variation for a same person undergoing confirmatory tests for a particular disease. The result can be within the reference range or outside the range. Majority of the well known laboratoriestry to ensure that all tests results from their machines are accurate and precise by providing values within the reference range.

Other factors affecting lab results

1. Diet and nutritional status such as fasting, calorie restriction, food exclusion diets, malnutrition and dehydration can affect the results.
2. The body is always changing and age, hormonal cycles, physical activity level, medications, lifestyle and evenseasonal changes can cause alterations in the body chemistry that will show up on a test result.
3. The stage of illness and the timing of tests can also affect results.

It is important to note that results are also affected by race, gender and other characteristics and can vary due to the time of the day the blood sample was drawn and whether the individual have taken food or not. The patient should not decide whether a result is correct based on his or her assumptions. Results should be reviewed by a doctor who is familiar with the different reference ranges and the disease(s) for which the result is being interpreted.

The clinician will interpret the results correlating to the patient’s clinical history and if needed, will advise to redo the test at another laboratory or the same laboratory if he or she feels that the values are not in-line with the diagnosis of the patient.