Inaccurate Lab Results

Posted by Elaine Moore Jun 14, 2006

It's normal to panic when you first see abnormal test results, especially if they're your own. But consider the fact that lab results may not be as ominous as they first appear when there are laboratory test interferences. Lab test interferences have two major causes: 1) substances or factors that cause temporary physiological changes in the body and thereby temporarily influence test results and 2) innocuous substances, for instance heterophile antibodies, that cause interferences with analytical assays, causing falsely elevated or decreased test results.

An example of a physiological effect is the temporary increase in platelets that occurs in conditions of sudden bleeding. In this case, a blood disorder causing thrombocytosis (increased platelet production) wouldn't be initially suspected unless a platelet count repeated after bleeding had subsided still showed an increased platelet count. An example of an interfering substance would be an abnormally increased thyroxine (T4) or free T4 (FT4) level in a pregnant patient with no symptoms of hyperthyroidism caused by the increased levels of binding proteins that normally occur in pregnancy. Another example of an interfering substance would be a marked elevated digoxin level on a patient on a low therapeutic dose of digoxin caused by mouse antibodies.

Many factors can influence blood test results and these factors must be taken into consideration when results are interpreted. Trauma patients, in particular, will have test results that reflect the body's attempt to shut down and prepare for death. The blood often hemoconcentrates causing the red blood cell count and hemoglobin to rise, similar to the elevations seen in dehydration. Patients who suddenly move to a high altitude will also have similar changes as their body adapts to thinner air.

Diet, exercise, illnesses, temperature, altitude, stress and medications all affect blood test results. A sudden increase in blood eosinophils may be related to parasitic infection, seasonal allergies, lymphoma or, more commonly, a reaction to medications or food allergens, even in the absence of rash. The dietary supplement tryptophan has been associated with a condition known as eosinophilic myalgia that resulted in 38 deaths in the 1980s. A contaminant caused the rise in eosinophils, which, in turn, released toxic factors that injured muscle, including heart muscle. In patients with autoimmune thyroid disease the presence of TSH receptor antibodies can suppress TSH, causing low TSH test results even when thyroid function is normal. When this is not understood, patients are often treated incorrectly for both conditions of hypothyroidism and hyperthyroidism. Although disclaimers are made for immunoassay test results to be interpreted with caution, they seldom are. A thorough medical evaluation and drug history should be correlated before interpreting abnormal test results.

Besides these types of interferences, the lab specimen itself may be responsible for abnormal results. For instances, blood specimens may be contaminated with heparin if they're drawn from a line resulting in abnormal tests for blood clotting, similar to what's seen in patients on aspirin therapy. Blood specimens may be also diluted with saline during line draws or inadvertently put into the wrong type of test tube, causing diluted or contaminated test results. Difficult blood draws can cause the red blood cells to rupture, resulting in hemolyzed specimens. Hemolyzed specimens can interfere with liver function tests and potassium levels. Specimens that are improperly handled after blood draw, standing too long before being centrifuged, for instance, can cause falsely decreased blood sugar and high potassium levels. Many test results, for instance triglyceride levels, are falsely elevated when the patient doesn't fast for 8-12 hours. On the other hand, increased fasting, longer than 12 hours for instance, can cause the liver to produce more cholesterol, falsely increasing levels.

Today's immunoassays used to detect hormones, tumor markers and therapeutic drug levels are most likely to be affected by non-human antibody testing interferences.

Heterophile antibodies and specific human anti-antimal antibodies (HAAAs) are antibodies produced during viral infection, bacterial infection, vaccination, or exposure to animals. Some patients have both heterorphile antibodies and HAAAs. These antibodies interfere with test results when antibodies of the species the antibodies are directed against are used to prepare test reagents. Heterophile antibodies to at least 4 different interfering species have been found to interfere with immunoassays. Historically, heterophile antibodies have been sheep cell agglutinins associated with mononucleosis.

The clinical significance of interfering substances is great, yet laboratory professionals do not have reliable ways to detect their presence. They must rely on the physician to question the results and either request tests for heterophile antibodies or HAAAs....or request that the test be performed at another institution using a different analytical testing method. In one well-publicized case, a patient sued the laboratory that released false pregnancy test results because the test for the hormone beta HCG that rises in pregnancy was affected by interfering substances.

Spurious laboratory results can lead to misdiagnosis and to inadequate disease management. Human anti-mouse antibody, in one patient, led to a false positive PSA result after radical prostate surgical removal. This resulted in over-treatment of the patient because of presumed cancer reoccurrence. Antibodies to Escherichia coli resulted in falsely elevated immunoassay results for six different hormones in one patient. Heterophile antibodies have also been found to interfere with the gold standard Western Blot assay used for the detection of HIV. These antibodies are also known to cause false positive HIV ELISA test results. Anti-murine antibodies have also been reported to interfere with cardiac marker tests for CK MB isoenzymes and troponin, causing a false diagnosis of myocardial infarction.

Resource:

Mildred Fleetwood, Interference in Clinical Laboratory Tests by Human Antibodies to Specific and Non-Specific Immunogens, Laboratory Medicine, April 2003.