Applied Evidence

Pitfalls & pearls for 8 common lab tests

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It can be tough to incorporate concepts like sensitivity, specificity, and positive and negative predictive value into everyday practice, but lab results may not be meaningful otherwise. Here’s what you need to know.




› When interpreting hemoglobin A1c (HbA1c) levels, assess for anemia and other comorbidities that can significantly affect the lifespan of red blood cells and skew HbA1c test results. B
› Order nonfasting lipid panels for patients for whom fasting laboratory tests are difficult to obtain, as they have good clinical utility in screening and initial treatment. A
› Avoid routine thyroid-stimulating hormone (TSH) testing in asymptomatic adults; when testing is indicated, start with TSH. A

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

Laboratory mistakes are not defined as diagnostic errors, but they contribute significantly to the thousands of medical errors that occur every year.1 Part of the problem: While accurate interpretation of lab tests often depends on the use of statistical concepts we all learned in medical training, it is difficult to find the time to incorporate these principles into a busy practice.

Overuse of lab tests presents problems, as well. Because “normal ranges” for test results are based on statistical analysis, as many as 5% of patients in a standard distribution fall outside of the range.2 It is important to order only the tests you really need, as extra testing automatically means more false positive results.

This article was written with such pitfalls in mind. In the pages that follow, we focus on 8 types of tests family physicians rely on regularly—all cases in which test results are reliable only if comorbidities, pre- and post-test probabilities, and clinical context are carefully considered. To help you put these lab tests into the proper context, we’ve addressed a key question—and highlighted both pitfalls and pearls—about each.

1. Hemoglobin A1c: How does anemia affect it?

Hemoglobin A1c (HbA1c) can be measured in many ways, including high-performance liquid chromatography, boronate affinity, capillary electrophoresis, and immunoassay, all of which can provide equivalent values without significant variability.3,4 In interpreting these tests, however, it is important to understand the effect that anemia has on HbA1c.

It's important to order only the tests you really need, as extra testing automatically means more false positive results.

Two primary variables influencing HbA1c are the average glucose level and the average lifespan of red blood cells (RBCs). Normally, there is a direct correlation between average serum glucose and HbA1c.4 In patients with anemia, however, this relationship is less clear, and may be affected by erythropoiesis and RBC destruction.5 In iron deficiency anemia (IDA),6,7 hemoglobin production falls secondary to iron stores, resulting in microcytic cells with a longer lifespan and elevated HbA1c. In at least one study,5,7 HbA1c approached levels associated with diabetes (with increases as high as 1.5%) in nondiabetic patients, but resolved with treatment of IDA.

Increased destruction as well as increased production of RBCs lowers their lifespan, and in turn decreases HbA1c levels (TABLE 1).4 This can be seen in conditions such as splenomegaly and hemoglobinopathies. In patients with hemoglobinopathies, the percentage of hemoglobin A is significantly decreased, often to undetectable levels—thereby making HbA1c tests inaccurate. Hemoglobin electrophoresis and determination of glycation by capillary electrophoresis or high-performance liquid chromatography can be used instead, but neither is practical because of cost and limited availability.4,8,9

THE TAKEAWAY: When you evaluate HbA1c test results, it is crucial to assess the patient for anemia and other conditions or comorbidities that can significantly affect RBC lifespan and skew test results.2,4-6

2. D-dimer: When should you use it?

D-dimer is a fibrin degradation product that is increased when active clotting is present,10 and its assay—which has high sensitivity and low specificity—is widely used to screen for pulmonary embolism (PE) and deep vein thrombosis (DVT). While the minimal number of false negatives makes the D-dimer a good screening test, the higher rate of false positives makes it difficult to arrive at a definitive diagnosis. Appropriate use of the D-dimer assay is crucial to minimize the potential for adverse consequences, such as bleeding in patients who are subjected to unnecessary anticoagulation because of false positive results.

Further testing typically follows. A positive D-dimer test is commonly followed by a computed tomography (CT) scan of the chest or a ventilation/perfusion scan to establish a PE or DVT diagnosis. But this subsequent testing increases both the cost of health care and the patient’s radiation exposure. Use of these subsequent scans can be reduced by first considering the patient’s pretest probability for PE or DVT. The Wells’ Criteria (available at and Geneva Score (Revised) ( can both be used for this purpose.10,11

Nonfasting lipid values can offer useful information—particularly in patients who are unwilling or unable to return for fasting labs.Patients with high pretest probability should undergo immediate scanning, foregoing the D-dimer—which should be reserved for patients who have a low or moderate pretest probability but sufficient reason to suspect PE or DVT.10-12


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