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The American Journal of Managed Care September 2010
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Mayer B. Davidson, MD; Maria Blanco-Castellanos, RN; and Petra Duran, BS
Organization of Care and Diagnosed Depression Among Women Veterans
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Jasvinder A. Singh, MD, MPH; Jeff A. Sloan, PhD; Pamela J. Atherton, MS; Tenbroeck Smith, MS; Thomas F. Hack, PhD; Mashele M. Huschka, BS, RN; Teresa A. Rummans, MD; Matthew M. Clark, PhD; Brent Diekmann, BS; and Lesley F. Degner, RN, PhD
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Scott D. Ramsey, MD, PhD; Jeannine S. McCune, PharmD; David K. Blough, PhD; Cara L. McDermott, BA; Lauren Clarke, MS; Jennifer L. Malin, MD, PhD; and Sean D. Sullivan, PhD
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Antiquated Tests Within the Clinical Pathology Laboratory
Alan H. B. Wu, PhD; Kent Lewandrowski, MD; Ann M. Gronowski, PhD; David G. Grenache, PhD; Lori J. Sokoll, PhD; and Barbarajean Magnani, PhD, MD
Magnitude and Economic Effect of Overuse of Antisecretory Therapy in the Ambulatory Care Setting
Joel J. Heidelbaugh, MD; Kathleen L. Goldberg, PharmD; and John M. Inadomi, MD

Antiquated Tests Within the Clinical Pathology Laboratory

Alan H. B. Wu, PhD; Kent Lewandrowski, MD; Ann M. Gronowski, PhD; David G. Grenache, PhD; Lori J. Sokoll, PhD; and Barbarajean Magnani, PhD, MD

Physicians and laboratorians must work to reduce use of antiquated clinical laboratory tests.

Objective: To provide evidence supporting the discontinuation of laboratory tests that do not have clinical utility today.


Study Design: We selected 10 representative tests considered antiquated by most experts in the clinical laboratory medicine field: creatine kinase-MB, myoglobin, serum folate and red blood cell folate, amylase, lecithin/sphingomyelin ratio, qualitative serum human chorionic gonadotropin, prostatic acid phosphatase, bleeding time, and erythrocyte sedimentation rate.


Methods: Published literature was reviewed to provide evidence of the poor performance and/or limited clinical utility of these tests. When available, subscriptions to the Proficiency Testing Program of the College of American Pathologists were tracked from 1993 to 2008 as supporting evidence. Finally, when appropriate, alternative testing was suggested.


Results: The data show clearly that there is a national trend toward reduction or elimination of these 10 tests.


Conclusion: Together with their clinical colleagues, clinical laboratorians should review their menu of tests and consider removing tests that do not provide clinical benefit. In most cases, alternative tests are already in clinical use.


(Am J Manag Care. 2010;16(9):e220-e227)

Although the clinical laboratory plays a critical role in management of patients in both disease and health, some tests have been replaced by others and no longer provide value.


  • Newer analytes such as troponin, prostate-specific antigen, and C-reactive protein have replaced creatine kinase-MB, myoglobin, and lactate dehydrogenase; prostatic acid phosphatase; and the erythrocyte sedimentation rate, respectively.


  • The need for folate testing has been dramatically reduced with the supplementation of dietary folic acid. n Testing technologies have improved, making bleeding time, the lecithin/sphingomyelin ratio, and amylase redundant or unnecessary.
Given the current economic climate for medical practices, it is the responsibility of clinical laboratory directors in hospitals and medical centers to review their test menu and, in collaboration with their clinical staff leaders, remove tests that do not provide clinical value to a particular medical practice, whether such testing is conducted in-house or sent to a reference laboratory. However, many physicians who are experienced with the use of older tests may resist adoption of newer technologies even if the tests have been shown to have superior clinical value or are recommended in contemporary clinical guidelines. Changing the testing menu can be a difficult process and should involve laboratorians and the medical staff, especially the staff who frequently order the tests that are to be eliminated. This article provides documentation for laboratorians who are considering the removal of tests from their menu and can serve as an educational platform for discussions with clinical colleagues.

Here we have selected 10 tests that most experts consider antiquated in clinical laboratory medicine: creatine kinase-MB (CK-MB), myoglobin, serum folate and red blood cell folate, amylase, lecithin/sphingomyelin (L/S) ratio, qualitative serum human chorionic gonadotropin (hCG), prostatic acid phosphatase, bleeding time, and erythrocyte sedimentation rate (ESR). There may be many other tests that can be eliminated after a systematic review. After examination of the literature, we have provided published evidence for these tests’ limited diagnostic and clinical utility. As supporting evidence, when possible, we have provided subscription trends from the College of American Pathologists (CAP) Proficiency Testing Program to examine trends in the subscription as a surrogate for the clinical utilization of these tests among participants. Finally, when appropriate, we have suggested  alternate testing that should replace the antiquated methods.


The use of CK-MB isoenzymes as markers for acute myocardial infarction (AMI) dates back to the early 1970s with enzymatic measurement by electrophoresis.1 Currently, most laboratories use the automated mass assays for CK-MB described in the mid-1980s.2 Release of CK-MB into the blood occurs in patients with heart or skeletal muscle injury or disease. A calculation of the CK-MB amount relative to total CK measurements (relative index) has been useful to differentiate the source of CK-MB release. Following AMI, there is a delay in the appearance of CK-MB due to its relatively large size (84 kDa). The clinical interest in myoglobin dates to the early 1990s with the development of automated  immunoassays.3 Myoglobin is a smaller protein than CK-MB (17 kDa) and is released into the blood sooner than CK-MB after the onset of AMI. Myoglobin also is released into the blood of patients with skeletal muscle injury, and the clearance of myoglobin is retarded in cases of renal damage. Each condition leads to increased blood concentrations. The isoenzymes of lactate dehydrogenase can differentiate between release of this enzyme because of cardiac damage and release from other organs such as the liver or lungs.

The development and implementation of, and continued improvements in, cardiac troponin have put in question the need for clinical laboratories to offer CK-MB, myoglobin, and lactate dehydrogenase isoenzymes. Unlike those biomarkers, release of troponin T or I is specific to cardiac injury. When the myocyte is irreversibly damaged, there is an initial rise in troponin due to its release from the free cytosolic pools, followed by a prolonged increase due to degradation of the myofibrils. Using first-generation assays, troponin becomes detectable in blood at the same time as CK-MB and remains elevated longer than CK-MB or lactate dehydrogenase.4 With improvements in analytical sensitivity and use of the 99th percentile as a cutoff limit for AMI, as recommended by the Task Force for the Redefinition of Myocardial Infarction,5 troponin is released before CK-MB and appears in the blood as early as if not earlier than myoglobin after AMI onset.6

Based on the CAP Cardiac Markers Survey (Table), utilization of CK-MB and myoglobin has undergone a gradual decline in subscriptions in recent years. In contrast, the corresponding proficiency survey subscription rate for cardiac troponin has remained steady or slightly increased (data not shown). Critics opposed to the removal of CK-MB and/or myoglobin argue that because troponin remains increased for 5 to 7 days, the test cannot determine the presence of a reinfarction. However, in a case series, Apple and Murakami showed that troponin tracks closely with CK-MB.7 Moreover, in a controlled coronary care unit environment, measurement of total CK, a test that is not considered obsolescent,can be used to detect a reinfarction. Total CK also can be important in the evaluation of patients with skeletal muscle injury and/or diseases such as Duchenne muscular dystrophy

or rhabdomyolysis.

Others have advocated retention of the CK-MB test to make estimates of infarct size. Such assessments require measurement of the area under the enzyme versus time curve, and are inaccurate when there is reperfusion of the target vessel. Cardiologists should not delay in treating patients to obtain peak CK-MB levels to document infarct size, as the objective of early intervention is to minimize the extent of myocardial damage. If determination of the severity of AMI is desired, some investigators have shown that single-point troponin measurements equate to infarct size.8 Today, myoglobin testing has largely been discontinued by clinical laboratories. It is likely that more laboratories will abandon CK-MB testing in the near future as well.


A deficiency in folic acid and vitamin B12 is one cause of macrocytic anemia. The detection of low folate concentrations in serum or red blood cells is useful for finding folic acid deficiencies. Red blood cell folate is thought to be more reflective of tissue stores, but requires an extraction step prior to analysis.9 In January and November 1998, the United States and Canada, respectively, mandated that foods with processed grains be fortified with folic acid. Dietary folate supplementation has resulted in a significant decline in the incidence of folate deficiency.10-13 The incidence of folic acid deficiency was even low in indigent patients, in whom dietary deficiency would be expected to be more prevalent.9 Therefore, routine screening of serum and/or red blood cell folate as a means to evaluate patients with anemia is difficult to justify. Shojania has shown that folate deficiency is also a rare cause of untreated celiac disease.14 For the rare patients suspected of such a deficiency, many clinicians now suggest that simply treating with folic acid is a more   cost-effective approach than blood testing.15 For laboratories testing international populations in which there is no folate supplementation, this testing may be warranted. If deficiencies are found, follow-up testing may be important to determine therapeutic efficacy of folate fortification.


Amylase and lipase are digestive enzymes normally released from the acinar cells of the exocrine pancreas into the duodenum. Following injury to the pancreas, these enzymes are released into the circulation and cause a subsequent increase in their measured activity. Both amylase and lipase are low-molecular- weight enzymes (40-50 kDa) and are filtered through the glomerulus. Amylase is cleared in the urine, whereas lipase is reabsorbed back into the circulation. In patients with acute pancreatitis, the activities are greatly increased in serum above the reference range. There is historic confusion regarding the clinical utility and enzyme profiles of amylase and lipase in acute pancreatitis.16 This confusion stems from the discovery that lipase assays devoid of colipase and bile salts were an insensitive and imprecise measure.17 As these constituents are now incorporated into all commercial reagents, lipase has clinical sensitivity equivalent to that of amylase and superior clinical specificity.18 For example, amylase is increased in patients with salivary gland inflammation.19 The salivary isoenzyme also can bind with immunoglobulin to form a macromolecular complex that is not cleared from the circulation, and persistent elevations are observed in the absence of pancreatic diseases.20 Werner et al showed that there was no diagnostic advantage to combining results of lipase and amylase tests compared with the clinical performance of the individual tests.21 The development of assays for the pancreatic amylase isoenzyme has improved the specificity of the test.22  However, if the objective of amylase and lipase testing is to detect pancreatic diseases, amylase provides redundant information and elimination of this test can be considered.

It should be noted that lipase and amylase testing is performed on routine clinical chemistry analyzers at minimal incremental reagent costs, and the cost savings to the laboratory in eliminating amylase will be marginal. Nevertheless, elimination of a nonspecific test may mean less diagnostic confusion and fewer unnecessary workups for a patient with a nonspecific increase in amylase activity. It also opens up a “reagent channel” on the chemistry analyzer that can be used for another test.


First reported in 1971, the L/S ratio, determined by thin-layer chromatography, was the first biochemical test for assessing the maturity of fetal lungs. Many outcome studies have demonstrated that the L/S ratio has good sensitivity (80%- 100%) and specificity (70%-97%).23 Because it was the first test developed, it was long considered to be the gold  standard for assessing fetal lung maturity. However, today, use of L/S testing has become largely obsolete and has mostly been replaced by fluorescent polarization and lamellar body counts.

Reports have suggested that the volume of all fetal lung maturity testing is decreasing nationally, with one laboratory demonstrating a 64% decrease in test volumes from 1994 to 2004.24 Among tests of fetal lung maturity, the frequency of L/S ratio testing in the United States has declined the most dramatically (Table). Results of a survey of 417 physicians indicated that their use of the L/S ratio had decreased by 70%, in contrast to a 35% decrease for fluorescence polarization.24 The reason for this dramatic decrease in the use of the L/S ratio is likely multifactorial.

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