Modern medicine relies extensively on the clinical laboratory as a key component of health care. It is estimated that in current practice, at least 60–70% of all clinical decisions rely to some extent on a laboratory result. For many diseases, the clinical laboratory provides essential diagnostic information. As an example, histopathologic analysis provides basic information about histologic type and classification of tumors and their degree of invasion into adjacent tissues. Microbiologic testing is required to identify infectious organisms and determine antibiotic susceptibility. For many common diseases, expert groups have produced standard guidelines for diagnosis that rely on defined clinical laboratory values, e.g., blood glucose or hemoglobin A1C levels form the basis for diagnosis of diabetes mellitus; the presence of specific serum antibodies is required for diagnosis of many rheumatologic diseases; and serum levels of cardiac markers are a mainstay in diagnosis of acute coronary syndromes.
The ever-increasing number and scope of clinical laboratory tests provides the clinician with a powerful set of tools but poses the challenge of appropriate selection of clinical laboratory tests in the most judicious and cost-effective way to deliver effective patient care.
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 sources such as the patient's history, physical examination findings, and imaging studies. The questions that need to be considered are which clinical laboratory tests could be of value in supporting, confirming, or excluding the clinical impression? What is the most efficient test-ordering strategy? If a test result is positive, will that confirm the clinical impression or even formally establish the diagnosis? If negative, does that disprove the clinical suspicion, and what further testing or approach is needed? What are the known sources of false-positive and false-negative results, and how does one recognize these?
Another reason for ordering clinical laboratory tests is screening for disease in asymptomatic individuals (Chap. 4). Perhaps the most common examples of this are the newborn screening programs now being 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. Screening of adults for the presence of diabetes mellitus, renal disease, prostate cancer [by testing serum prostate-specific antigen (PSA) levels], and colorectal cancer (by testing for occult blood in stool) are examples of widely used clinical laboratory screening procedures that are applied to apparently healthy individuals on the basis that early diagnosis and intervention in patients with these diseases leads 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 for screening 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 testing personnel. As a general principle, screening tests are designed to identify all subjects who have the disease of interest, even if that means incorrectly labeling some healthy individuals as possibly having disease. Stated more formally, the diagnostic sensitivity of screening tests is maximized and this inevitably comes at the expense of reduced diagnostic specificity. Confirmatory testing is intended to correctly separate those individuals with disease from those who do not have disease.
As an example of these principles, when screening for hepatitis C viral (HCV) infection, a common approach is to first test for the presence of anti-HCV antibodies in a patient's 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, anti-HCV antibodies may persist and be detectable for life. However, a small number of patients will have false-positive results in the serologic screening test for HCV. To resolve these uncertainties, a positive serologic screening test should be followed by confirmatory identification of hepatitis C viral RNA using molecular techniques. This confirmatory testing can provide evidence of current viral infection or identify patients who are not infected.
Risk Assessment of Future Disease
Another reason for clinical laboratory testing is assessing a patient's risk of developing disease in the future. A number of diseases are associated with well-established clinical laboratory-defined risk factors, which, if present, would indicate the need for more frequent monitoring for disease. The need for risk assessment is even clearer if there are also 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 (Chap. 241). Many genetic mutations are known to be associated with increased risk of cancer, such as hereditary mutations in the BRCA1 and BRCA2 genes, which 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 attempt to prevent cancer (Chap. 63). Individuals with factor V Leiden are at increased risk of developing deep venous thrombosis and may benefit from prophylactic anticoagulation in the perioperative period. For example, some types of surgery, such as hip replacement, are accompanied by prolonged immobilization, which is itself an additional risk for deep venous thrombosis.
Monitoring Disease and Therapy
Many clinical laboratory tests offer useful information on the progress of disease and the response to therapy. As an example, one might consider the role of viral load measurements in patients with HIV-1 infection who are on anti-retroviral agents. According to current Centers for Disease Control (CDC) guidelines, a successful anti-retroviral response is defined by a fall in plasma HIV-1 levels of 0.5 log...