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Managed Care & Healthcare Communications n TRENDS FROM THE FIELD n 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 iven the current economic climate for medical practices, it Objective: To provide evidence supporting the discontinuation of laboratory tests that do not is the responsibility of clinical laboratory directors in hos- have clinical utility today. G pitals and medical centers to review their test menu and, Study Design: We selected 10 representative tests in collaboration with their clinical staff leaders, remove tests that do considered antiquated by most experts in the clinical laboratory medicine field: creatine kinase- not provide clinical value to a particular medical practice, whether MB, myoglobin, serum folate and red blood cell such testing is conducted in-house or sent to a reference laboratory. folate, amylase, lecithin/sphingomyelin ratio, qualitative serum human chorionic gonadotropin, However, many physicians who are experienced with the use of older prostatic acid phosphatase, bleeding time, and tests may resist adoption of newer technologies even if the tests have erythrocyte sedimentation rate. been shown to have superior clinical value or are recommended in Methods: Published literature was reviewed to provide evidence of the poor performance and/ contemporary clinical guidelines. Changing the testing menu can be or limited clinical utility of these tests. When a difficult process and should involve laboratorians and the medical available, subscriptions to the Proficiency Testing Program of the College of American Pathologists staff, especially the staff who frequently order the tests that are to were tracked from 1993 to 2008 as supporting be eliminated. This article provides documentation for laboratori- evidence. Finally, when appropriate, alternative testing was suggested. ans who are considering the removal of tests from their menu and Results: The data show clearly that there is a can serve as an educational platform for discussions with clinical national trend toward reduction or elimination of colleagues. these 10 tests. Here we have selected 10 tests that most experts consider anti- Conclusion: Together with their clinical colleagues, clinical laboratorians should review their menu quated in clinical laboratory medicine: creatine kinase-MB (CK-MB), of tests and consider removing tests that do not myoglobin, serum folate and red blood cell folate, amylase, lecithin/ provide clinical benefit. In most cases, alternative tests are already in clinical use. sphingomyelin (L/S) ratio, qualitative serum human chorionic gonado- (Am J Manag Care. 2010;16(9):e220-e227) tropin (hCG), prostatic acid phosphatase, bleeding time, and eryth- rocyte 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.© Managed Finally, when appropriate, Care we& have suggested alter- Healthcarenate testing that should Communications, replace the antiquated methods. LLC CREATINE KINASE-MB AND MYOGLOBIN The use of CK-MB isoenzymes as markers for acute myocardial infarction (AMI) dates back to the early 1970s with enzymatic mea- surement by electrophoresis.1 Currently, most laboratories use the automated mass assays for In this article Take-Away Points / e221 For author information and disclosures, CK-MB described in the mid- see end of text. Published as a Web Exclusive 1980s.2 Release of CK-MB into www.ajmc.com e220 n www.ajmc.com n SEPTEMBER 2010 Antiquated Tests the blood occurs in patients with heart or skeletal muscle injury or disease. A Take-Away Points Although the clinical laboratory plays a critical role in management of patients in both dis- calculation of the CK-MB amount rela- ease and health, some tests have been replaced by others and no longer provide value. tive to total CK measurements (relative n Newer analytes such as troponin, prostate-specific antigen, and C-reactive protein have index) has been useful to differentiate replaced creatine kinase-MB, myoglobin, and lactate dehydrogenase; prostatic acid phos- phatase; and the erythrocyte sedimentation rate, respectively. the source of CK-MB release. Following n The need for folate testing has been dramatically reduced with the supplementation of AMI, there is a delay in the appearance dietary folic acid. of CK-MB due to its relatively large size n Testing technologies have improved, making bleeding time, the lecithin/sphingomyelin ratio, and amylase redundant or unnecessary. (84 kDa). The clinical interest in myo- globin dates to the early 1990s with the development of automated immunoas- says.3 Myoglobin is a smaller protein than CK-MB (17 kDa) injury and/or diseases such as Duchenne muscular dystrophy and is released into the blood sooner than CK-MB after the or rhabdomyolysis. onset of AMI. Myoglobin also is released into the blood of Others have advocated retention of the CK-MB test to patients with skeletal muscle injury, and the clearance of make estimates of infarct size. Such assessments require mea- myoglobin is retarded in cases of renal damage. Each condi- surement of the area under the enzyme versus time curve, and tion leads to increased blood concentrations. The isoenzymes are inaccurate when there is reperfusion of the target vessel. of lactate dehydrogenase can differentiate between release of Cardiologists should not delay in treating patients to obtain this enzyme because of cardiac damage and release from other peak CK-MB levels to document infarct size, as the objective organs such as the liver or lungs. of early intervention is to minimize the extent of myocardial The development and implementation of, and continued damage. If determination of the severity of AMI is desired, improvements in, cardiac troponin have put in question the some investigators have shown that single-point troponin need for clinical laboratories to offer CK-MB, myoglobin, and measurements equate to infarct size.8 Today, myoglobin test- lactate dehydrogenase isoenzymes. Unlike those biomarkers, ing has largely been discontinued by clinical laboratories. It release of troponin T or I is specific to cardiac injury. When is likely that more laboratories will abandon CK-MB testing the myocyte is irreversibly damaged, there is an initial rise in the near future as well. 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 SERUM FOLATE AND RED detectable in blood at the same time as CK-MB and remains Blood CELL FOLATE 4 elevated longer than CK-MB or lactate dehydrogenase. A deficiency in folic acid and vitamin B12 is one cause With improvements in analytical sensitivity and use of the of macrocytic anemia. The detection of low folate concen- 99th percentile as a cutoff limit for AMI, as recommended by trations in serum or red blood cells is useful for finding fo- the Task Force for the Redefinition of Myocardial Infarction,5 lic acid deficiencies. Red blood cell folate is thought to be troponin is released before CK-MB and appears in the blood more reflective of tissue stores, but requires an extraction as early as if not earlier than myoglobin after AMI onset.6 step prior to analysis.9 In January and November 1998, the Based on the CAP Cardiac Markers Survey (Table), uti- United States and Canada, respectively, mandated that foods lization of CK-MB and myoglobin has undergone a gradual with processed grains be fortified with folic acid. Dietary fo- decline in subscriptions in recent years. In contrast, the cor- late supplementation has resulted in a significant decline in responding proficiency survey subscription rate for cardiac the incidence of folate deficiency.10-13 The incidence of folic troponin has remained steady or slightly increased (data not acid deficiency was even low in indigent patients, in whom shown). Critics opposed to the removal of CK-MB and/or dietary deficiency would be expected to be more prevalent.9 myoglobin argue that because troponin remains increased for Therefore, routine screening of serum and/or red blood cell 5 to 7 days, the test cannot determine the presence of a re- folate as a means to evaluate patients with anemia is difficult infarction. However, in a case series, Apple and Murakami to justify. Shojania has shown that folate deficiency is also a showed that troponin tracks closely with CK-MB.7 Moreover, rare cause of untreated celiac disease.14 For the rare patients in a controlled coronary care unit environment, measure- suspected of such a deficiency, many clinicians now suggest ment of total CK, a test that is not considered obsolescent, that simply treating with folic acid is a more cost-effective can be used to detect a reinfarction. Total CK also can be approach than blood testing.15 For laboratories testing inter- important in the evaluation of patients with skeletal muscle national populations in which there is no folate supplementa- VOL. 16, NO. 9 n THE AMERICAN JOURNAL OF MANAGED CARE n e221 n TRENDS FROM THE FIELD n n Table. Enrollments in the College of American Pathologists Proficiency Surveys for Selected Laboratory Analytes CK-MBa L/S Ratiob Acid Phosphatasec RBC Folated ESRe Year No. Year No. Year No. Year No. Year No. 1993 3046 1994 218 — — — — — — 1996 3234 1996 262 1996 372 1997 244 — — 1999 3531 1999 189 1999 274 1999 355 1999 4114 2002 3411 2002 138 2002 142 2002 258 2002 3484 2005 2706 — — 2005 95 2005 273 2005 2825 2008 2723 2007 71 2008 46 2008 230 2008 3138 2010 2741 2010 49 2010 35 2010 236 2010 3513 CK-MB indicates creatine kinase-MB; ESR, erythrocyte sedimentation rate; L/S, lecithin/sphingomyelin; RBC, red blood cell.
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