College of American Pathologists
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  Q & A





cap today

February 2002

Q.  When will a vaccine be available for hepatitis C?

A.  The prospect for a traditional inactivated (killed) or attenuated live hepatitis C virus vaccine is not immediate. Even if every ongoing research study were to have the optimal outcome and every regulatory and manufacturing process were on the fastest track imaginable, no candidate vaccine could be approved and ready for routine use within five years.

The principal scientific impediment is the propensity of HCV to mutate and, thus, the inability of traditional vaccines to induce protective immunity. Other limitations are the scarcity of chimpanzees, the only animal model for studying HCV infection, and the absence of an efficient HCV culture system for propagating HCV and testing neutralizing antibodies. New approaches to vaccine development, such as subunit, recombinant virus, or DNA vaccines, offer promise, but it’s too early to predict their efficacy. Lastly, there is the possibility that preventive immunity may not be necessary if a novel vaccine could induce an immune response—even after HCV infection—that would contain replication and prevent chronic infection and cirrhosis, the major cause of HCV-related morbidity and mortality.

S. Gerald Sandler, MD
Professor of Medicine and Pathology
Director, Transfusion Medicine
Georgetown University Hospital
Washington, DC

Q.  How valid are results on lipid profiles that are done on ICU patients the day after admission? These patients usually come in with chest pain. They are on IV solutions. They may have been vomiting and in discomfort. Should we attach a disclaimer to patient results that are done under other than "normal conditions"? Or are these orders reasonable for patient care?

A.  These questions are important ones and are oftentimes neglected issues that are encountered almost every day in clinical practice. Over the last decade we have seen significant improvements in the methods, instruments, and calibration materials used to enhance the accuracy of lipid and lipoprotein measurements in the clinical laboratories. From an analytical standpoint, the manufacturers’ participation in the National Heart, Lung, and Blood Institute-Centers for Disease Control and Prevention Standardization Program for lipids and lipoproteins has resulted in their analytical testing systems becoming certified because the accuracy of testing can be traced to approved reference methods and calibrating materials.

Today, the biggest sources of error are preanalytical issues, which can contribute to more than 50 percent of the total variation that can influence the lipid and lipoprotein test results on serial specimens collected from one person.1 The work of Smith et al2 demonstrated that the average intra-individual variation for serum total cholesterol is 6.1 percent; for LDL-cholesterol, 9.5 percent; for HDL-cholesterol, 7.4 percent; and for triglycerides, 22.6 percent. This makes it difficult to classify coronary heart disease, develop appropriate treatment strategies, and assess the efficacy of treatment. Ironically, many of the intra-individual variations can be minimized or avoided.

It is wise to measure the blood lipids and lipoproteins only during a patient’s steady state or while the patient is healthy with no metabolic distress.3 Any patient in the hospital (especially if they are in the ICU, CCU, ATU, or ER) should not be tested for lipids and lipoprotein profiling. It is well established that during times of infections, MI, stroke, surgical recovery, physical trauma, and other conditions that do not represent a person’s normal metabolic state, the test results are inaccurate and do not reflect the values obtained during steady state. Furthermore, any untreated secondary causes of dyslipoproteinemia should be first identified and then appropriately treated. They could come from secondary conditions such as hormonal imbalances, nephrotic syndrome, diabetes mellitus, or uncontrolled hypertension, or from excessive weight change during a short period or major dietary changes. The use of IV solutions compounds these problems by causing further inaccuracies in the test results because of hemodilution effects. Acute bouts of vomiting can cause dehydration and, thus, hemoconcentration, which falsely elevates analyte values.

It is always best not to do any lipid and lipoprotein testing for inpatients. One should safely wait four to six weeks after hospital discharge to do measurements with patients who are in a more stable metabolic state. Any behavioral or clinical sources of variation should be noted and, if possible, eliminated before the serum specimen is collected.4 The patient should maintain his or her normal lifestyle and should not gain or lose weight around the time the blood specimen is collected. The patient should also be advised to abstain from drinking alcohol for two to three days before the specimen is collected. An overnight fasting specimen is desirable for the measurement of the lipids and lipoproteins when profiling the patient. 5

No medical decision should be based on a single measurement. Because of the preanalytical sources of variation and the laboratory analytical variation, at least two serial specimens should be measured for the majority of individuals. 6,7 Cooper et al 8 calculated the total percent error (NCEP total analytic error + biological variation) for two separate measurements for total cholesterol to be 12.4 percent, LDL-C to be 18.6 percent, for HDL-C to be 23.6 percent, and triglycerides to be 37.0 percent. In other words, if the mean differences on the repeated measurement values exceed the total percent error values, another measurement should be taken.

Finally, if the patient’s specimen was analyzed, it would be prudent to put a disclaimer on the inpatient’s inaccurate lipid and lipoprotein test values because the patient was not in a stable metabolic condition when the measurements were done.

1.  Cooper GR, Myers GL, Smith SJ, et al. Blood lipid measurements: variations and practical utility. JAMA. 1992;267: 16521660.
2.  Smith SJ, Cooper GR, Myers GL, et al. Biological variability in concentrations of serum lipids: sources of variation among results from published studies and composite predicted values. Clin Chem. 1993;39:1012-1022.
3.  Naito HK. Cholesterol: How do we manage laboratory and patient health data? In: Martin ML, Addison BV, Wagner WM, et al, eds. 1989 Institute on Critical Issues in Health Laboratory Practice: Improving the Quality of Health Management Through Clinician and Laboratorian Teamwork. Wilmington, Del.: The Du Pont Co.; 1991:63-70.
4.  National Heart, Lung, and Blood Institute. Recommendations for improving cholesterol measurement: a report from the Laboratory Standardization Panel of the National Cholesterol Education Program. Bethesda, Md.: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, 1990; Publication No. 90-2964.
5.  Executive summary of the third report of the National Cholesterol Education Program expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285: 2486-2497.
6.  Cooper GR, Myers GL, Smith SJ, et al. Standardization of lipid, lipoprotein, and apolipoprotein measurements. Clin Chem. 1988;33:B95-B105.
7.  Brookstein L, Gidding SS, Donovan M, et al. Day-to-day variability of serum cholesterol, triglycerides, and high-density lipoprotein cholesterol levels. Arch Intern Med. 1990;150:1653-1657.
8.  Cooper RG, Smith SJ, Myers GL, et al. Estimating and minimizing effects of biologic sources of variation by relative range when measuring the mean serum lipids and lipoproteins. Clin Chem. 1994;40:227-232.

Herbert K. Naito, PhD
Chief, Ancillary Testing and Satellite Facilities
Pathology and Laboratory Medicine Service
Louis Stokes Cleveland Veterans
Affairs Medical Center