FALTs: Factors Affecting Laboratory Tests

FALTs: Factors Affecting Laboratory Tests

L. V. Rao


Laboratory testing is an integral part of modern medical practice. Although clinical laboratory testing accounts for only 2.3% of annual health care costs in the United States, it plays a major role in the clinical decisions made by physicians, nurses, and other health care providers for the overall management of disease. More than 4,000 laboratory tests are available for clinical use, and about 500 of them are performed regularly. The number of Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories has grown to exceed more than 200,000. The laboratory medicine workforce comprises pathologists, doctoral-level laboratory scientists, technologists, and technicians, who play a vital role in the health care system.

The health care system is increasingly dependent on reliable clinical laboratory services; however, as part of the overall health care system, these laboratory evaluations are prone to errors. Laboratory medicine comprises more than just the use of chemicals and reagents for the measurement of various analytes for clinical diagnosis purposes. Interference by both endogenous and exogenous substances is a common problem for the test analysis. These substances play a significant role in the proper interpretation of results, and such interference is adverse to patient care and adds to the cost of health care. It would be an oversimplification to conclude that each variable will always produce a specific effect; it depends on the person, the duration of exposure to that variable, and the time between initial stress, the sample collection, and the degree of exposure. Awareness that many factors occurring outside the laboratory in and around
the patient may affect the test result before the sample reaches the laboratory or even before the sample is collected is very important. These factors can be minimized when the clinician takes a good history and when there is a good communication of such information between the laboratory and the physician.


The total testing process defines the preanalytic, analytic, and postanalytic phases of laboratory testing and serves as the basis for designing and implementing interventions, restrictions, or limits that can reduce or remove the likelihood of errors. Over the last several years, there has been a remarkable decrease in error rates, especially analytic errors. Evidence from recent studies demonstrates that a large percentage of laboratory errors occur in preanalytic and postanalytic steps. Errors in the preanalytic (61.9%) and postanalytic (23.1%) processes occurred much more frequently than occurrences of analytic errors (15%). About one fourth of these can have consequences to the patient either in delay of the test result or life-threatening.


Preanalytic factors act on both the patient and the specimen before analyses. It is a complex and dynamic process differing from one hospital to another. It can cause random errors, undetectable by routine quality control and often unknown to testing personnel and clinicians. These factors may be divided further into those acting in vivo (biologic or physiologic) and those acting in vitro (specimen handling and interference factors). See Table 1-1 for some of the most frequently ordered tests, and their limitation causes false positive and false negative test results.


Some physiologic factors are beyond our control. They include age, sex, and race, and so on, and can be managed by placing appropriate reference limits. Others factors such as diet, starvation, exercise, posture, diurnal and seasonal variations, menstrual cycle, and pregnancy must be considered in the interpretation of the test results. Age has a noticeable effect on some test results and the need for establishing appropriate reference intervals. In newborns, the composition of blood is affected by the maturity of the infant at birth. At birth, RBC and hemoglobin values are higher than adults due to low levels of oxygen in the uterus. They continue to decrease and level out to adult values about the age of 15. Adult values are usually taken as the reference for comparison with those of the young and the elderly. The concentration of most test constituents remains constant between puberty and menopause in women and between puberty and middle age in men. The plasma concentrations of many constituents increase in women after menopause. Hormone levels are affected by aging. However, changes in concentrations are much less pronounced than an endocrine organ’s response to stimuli. Until puberty, there are few differences in laboratory data between boys and girls. After puberty, the characteristic changes in the levels of sex hormones become apparent.

TABLE 1-1. Preanalytic Factors Affecting Laboratory Tests


Normal Range


Falsely Increased

Falsely Decreased


<46 pg/mL

Significant diurnal variations, high in the morning (6-8 AM). Releases in bursts, levels vary by minute.

Pregnancy, menstruation, stress, rheumatoid factor

Patients taking glucocorticoids


0-4 mo: 2.0-4.5 g/dL

4 mo-16 y: 3.2-5.2 g/dL

>16 y: 3.5-4.8 g/dL

Two dye-binding methods, bromocresol green (BCG) and bromocresol purple (BCP), are in routine use.

BCG overestimates albumin in serum due to poorer specificity for the analyte.

BCP underestimates in pediatric patients on hemodialysis and chronic renal failure.

Alkaline phosphatase

0-1 y: 150-350 IU/L

1-16 y: 30-300 IU/L

>16 y: 30-115 IU/L

Day-to-day variations (5-10%)

Higher in African American men (15%) and women (10%) compared to other racial/ethnic groups

Recent food ingestion, smoking, increased BMI (25%), drugs: penicillin, antiepileptic drugs, antihistamines, cardiovascular drugs

Use of oral contraceptives

AFP, tumor marker

0.6-6.60 ng/mL

Not recommended as a screening procedure to detect cancer in the general population

Tumors of the GI tract, liver damage (e.g., cirrhosis, hepatitis, or drug or alcohol abuse), and pregnancy

Smoking tobacco (10%)

Inflammatory bowel disease

Some dietary supplements, herbal remedies, and vitamins can cause liver toxicity, leading to a rise in AFP levels.



<50 µmol/L

Not useful to assess the degree of dysfunction (e.g., in Reye syndrome, hepatic function improves and the ammonia level falls, even in patients who finally die of these disorders)

Levels are not always high in all patients with urea cycle disorders.

Atmospheric ammonia

The presence of ammonium ions in anticoagulants

High-protein diet, GI hemorrhage, increases due to cellular metabolism: 20% in 1 h and 100% by 2 h, prolonged tourniquet application




Not recommended as a general screening test

Depending on the titer, normal healthy population can have 5-20% positive test results.

Drugs (carbamazepine, chlorpromazine, ethosuximide, hydralazine, isoniazid, mephenytoin, methyldopa, penicillins, phenytoin, primidone, procainamide, and quinidine)

Viral illness and infections


Bilirubin total and direct

0-1 d: 0.0-6.0 mg/dL

1-2 d: 0.0-8.0 mg/dL

2-5 d: 0.0-12.0 mg/dL

5 d-4 mo: 0.3-1.2 mg/dL

>4 mo: 0.3-1.2 mg/dL

Direct bilirubin

0.0-0.4 mg/dL

Day-to-day variation (15-30%)

Lower in African Americans

Fasting up to 48 h

Exposure to light


Acetyl salicylic acid


Calcium, total

8.7-10.7 mg/dL

Need to interpret with total protein and albumin levels

0.8 mg of calcium is bound to 1.0-g albumin in serum. To correct, add 0.8 mg/dL for every 1.0 g/dL that serum albumin falls below 4.0 g/dL.


Multiple myeloma

Waldenström macroglobulinemia


Venous stasis during blood collection by prolonged application of tourniquet

Hyponatremia (<120 mmol/L)


Hyperphosphatemia (e.g., laxatives, phosphate enemas, chemotherapy of leukemia or lymphoma, rhabdomyolysis)



CO2, total

0-2 y: 20-25 mmol/L

2-16 y: 22-28 mmol/L

>16 y: 24-32 mmol/L

80-90% present as bicarbonate and is general guide to body’s buffering capacity



Mercurial and thiazide diuretics

Sodium bicarbonate



Ammonium chloride, aspirin, chlorothiazide diuretics, methicillin

Paraldehyde, tetracycline

High altitudes


0-35 U/mL

Not recommended for screening asymptomatic women

Not increased in mucinous adenocarcinoma

Different manufacturer assays do not produce similar value. Should not be used interchangeably.


Menstruation, endometriosis

Pleural effusion or inflammation

Peritoneal effusion or inflammation, cirrhosis, severe liver necrosis (66%), disorders of the GI tract, liver, and pancreas

Renal failure, healthy persons (1%)

Postmenopausal women

African American and Asian women

Cholesterol, total

<200 mg/dL

Intraindividual variation (10%)

Seasonal variation (8%) higher in the winter than in summer

Positional variation is 5% and 10-15% lower when phlebotomized sitting or recumbent, respectively, as opposed to standing.

Pregnancy, drugs: beta blockers, anabolic steroids, vitamin D, oral contraceptives, and epinephrine

Smoking, alcohol, renal failure

Hypothyroidism, glycogen storage disease, biliary cirrhosis, hepatocellular disease

Prostate and pancreatic neoplasms

Acute illness such as a heart attack


Liver disease

Myeloproliferative diseases

Chronic anemias





<10 mg/L

Not a screening test for wellness and should only be used in the diagnosis and monitoring of a patient who appears to have an inflammatory process

Elevated levels are nonspecific and should not be interpreted without a complete clinical history.

Influenced by genetics, age, and sedentary lifestyle, stress, exposure to environmental toxins, and diet that specifically contains refined, processed, and manufactured foods

Oral contraceptives


Monoclonal gammopathy

Patients treated with carboxypenicillins

Liver failure


0-15 mm/h in men 0-20 mm/h in women

Not a good screening test

Compared to the ESR, CRP is a more sensitive and specific marker of the acute phase reaction and is more responsive to changes in the patient’s condition.

There are only two circumstances where the erythrocyte sedimentation rate is superior—detecting low-grade bone and joint infections and monitoring disease activity in systemic lupus erythematosus.

Increased fibrinogen; increased gamma- and beta globulins

Drugs (dextran, penicillamine, theophylline, vitamin A, methyldopa, methysergide)

Technical factors (e.g., hemolyzed sample, high temperature in the laboratory)


Abnormally shaped RBCs (sickle cells, spherocytes, acanthocytes)

Microcytosis, HbC disease, hypofibrinogenemia

Technical factors (low temperature in the laboratory, clotted blood)

Extreme leukocytosis

Drugs (quinine, salicylates, high steroid levels, drugs that cause high glucose levels)


Male: 23-336 ng/mL (in patients with normal iron stores, it should be >30 ng/mL)

Female: 11-306 ng/mL

In hepatic, malignant, and inflammatory conditions, ferritin levels can be normal. In such cases, bone marrow stain of iron may be used to exclude iron deficiency.


Liver and kidney disease, malignancy

Obesity and age

Alcohol use



Sensitive but nonspecific indicator of biliary disease

Half-life (7-10 d); in alcoholassociated liver injury, the half-life is increased to as much as 28 d, suggesting impaired clearance.

Day-to-day variations (10-15%); approximately double in African Americans

Higher BMI (25-50%)

Renal disease

Cardiac disease


Pregnancy (25%)



Approximately one third of all conceptions end in natural termination. This may produce positive results when testing early in the pregnancy followed by negative results after the natural termination.

Marijuana use

Human antimouse antibody (HAMA) or heterophilic antibody

Elevated LH levels due to low testosterone can lead to false positives.

Duodenal ulcers

Cirrhosis of the liver

Inflammatory bowel disease

Smoking tobacco (20%)

False negatives in urine tests can be caused by drinking large amounts of fluids and taking diuretics, anticonsultants, anti-Parkinson drugs, tranquilizers, hypnotics, or certain antihistamines before the test.


0-50 U/L

More specific for pancreatitis than is for serum amylase; diagnosis of peritonitis, strangulated or infarcted bowel, pancreatic cyst

Cholinergic drugs, opiates


Renal disease



Intravenous dextrose




12-65 pg/mL

Inherent biologic variability due to hormone pulsatility and diurnal variation, choice of tube for sample collection, as well as sample stability at storage temperature

Because of a pronounced nocturnal rise in intact PTH levels observed in a small experimental male population, sampling after 10 AM for optimum discrimination between normal and those with mild primary hyperparathyroidism has been suggested.

Heterophile antibodies

Rheumatoid factor

Sedative-hypnotic drug propofol (Diprivan)


<4 ng/mL

Ambulatory values are higher than sedentary values, which may decrease ≤50% (mean = 18%).

Methodologic variations exist depending upon calibrators (WHO vs. Hybritech) used by various manufacturers (22% average bias).

Prostatic massage, ≤2 times

Cystoscopy: 4 times

Needle biopsy: >50 times for ≤1 mo

Transurethral resection: >50 times, digital rectal examination, indwelling catheter

Vigorous bicycle exercise: ≤2-3 times several days, ejaculation within 24-48 h

Urinary tract infection


Antiandrogen drugs (e.g., finasteride)

Radiation therapy


PSA falls 17% in 3 d after lying in hospital


0.5-6.3 µIU/mL, depending on age and sex

Not be useful for hospitalized ill patients. Has a diurnal rhythm (50%), with peaks at 2:00-4:00 AM and troughs at 5:00-6:00 PM with ultradian variations



Rheumatoid factor

Human antimouse antibodies

Heterophile antibodies

Thyroid hormone autoantibodies


Severe dehydration

Biotin may cause falsely low values in immunometric assays.

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Mar 20, 2021 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on FALTs: Factors Affecting Laboratory Tests

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