One of the most frequent reasons for performing clinical laboratory tests is to support, confirm, or refute a diagnosis of disease that is suspected based on other information sources, such as history, physical examination findings, and imaging studies. The following questions need to be considered: Which clinical laboratory tests may be of value in supporting, confirming, or excluding the clinical impression? What is the most efficient test-ordering strategy? Will a positive test result confirm the clinical impression or even definitively establish the diagnosis? Will a negative result disprove the clinical suspicion, and, if so, what further testing or alternative approach will be needed? What are the known sources of false-positive and false-negative results, and how are these misleading results recognized?
Another reason for ordering clinical laboratory tests is to screen for disease in asymptomatic individuals (Chap. 4). Perhaps the most common examples of this application are the newborn screening programs now routinely used in most developed countries. Their purpose is to identify newborns with treatable conditions for which early intervention—even before clinical symptoms develop—is known to be beneficial. In adults, screening tests for diabetes mellitus, renal disease, prostate cancer (measurement of serum prostate-specific antigen [PSA] levels), and colorectal cancer (testing for occult blood in stool), for example, are widely applied to apparently healthy individuals because early diagnosis and intervention lead to improved long-term outcomes.
Differences between Screening Tests and Confirmatory Tests
It is important to distinguish between clinical laboratory tests that can be used to screen for disease and those that offer a confirmatory result. Screening tests are generally less expensive and more widely available than are confirmatory tests, which often require more specialized equipment or personnel. As a general principle, screening tests are designed to identify all individuals who have the disease of interest, even if, in the process, some healthy individuals are misidentified as possibly having the disease. In other words, maximization of the diagnostic sensitivity of screening tests inevitably comes at the expense of reduced diagnostic specificity. Confirmatory testing is intended to correctly separate those individuals who have a disease from those who do not.
These principles are exemplified by screening for hepatitis C virus (HCV) infection. A common approach is to test first for the presence of antibodies to HCV in serum. A positive result generally indicates either a current infection or a previous infection that the patient’s immune system has successfully cleared. In the latter situation, antibodies may persist at detectable levels for life. However, a small proportion of patients have false-positive results in the serologic screening test for HCV. To resolve uncertainty in these instances, a positive serologic screening test should be followed by confirmatory identification of HCV RNA with molecular techniques. This confirmatory testing can provide evidence of current viral infection and can identify patients who are not infected.
RISK ASSESSMENT OF FUTURE DISEASE
Another reason for clinical laboratory testing is to assess a patient’s risk of developing disease in the future. Many diseases are associated with well-established clinical laboratory–defined risk factors that, if present, indicate the need for more frequent monitoring for the disease in question. The need for risk assessment is even clearer if there are useful interventions that decrease the risk of developing disease. For example, hypercholesterolemia is a well-established risk factor for coronary artery disease that may be modified by pharmacologic intervention. Many genetic mutations are known to be associated with increased risk of cancer. For example, hereditary mutations in the BRCA1 and BRCA2 genes predispose to breast and/or ovarian cancer. Individuals who are known to carry these mutations require more vigilant monitoring for early signs of cancer and may even opt for prophylactic surgery in an effort to prevent cancer (Chap. 457). Individuals with factor V Leiden are at increased risk of developing deep-venous thrombosis and may benefit from prophylactic anticoagulation, especially in settings that pose additional risk of venous thromboembolism, for example, in the perioperative period.
MONITORING DISEASE AND THERAPY
Many clinical laboratory tests offer useful information on the progress of disease and the response to therapy. One example is the measurement of viral load in HIV-1-infected patients who are taking antiretroviral agents. A key goal of treatment is a reduction in the viral load to below the level of laboratory detection, which is typically in the range of 40–50 copies/mL. Other examples of the use of clinical laboratory testing for monitoring disease include measurement of tumor markers such as PSA, especially following surgical removal of tumors. In this situation, the expectation is that successful treatment of a tumor will cause a decrease in the level of the tumor marker. A later increase in the level of the tumor marker suggests a recurrence of the disease. Finally, the clinical laboratory offers direct monitoring of levels of some therapeutic agents, such as drugs. This monitoring is important if a drug has a defined therapeutic concentration range above which it is toxic and below which it is ineffective. Monitoring of drug levels in this situation facilitates optimal dosing and avoidance of toxicity.