College of American Pathologists
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  Q & A





cap today

August 2002

Q.  Does the CAP still require checking positive urine proteins with sulfo-salicylic acid? I cannot find this in the current checklists.

A.  The old CAP checklist question about confirming positive dipstick protein results with a wet-chemistry method, such as sulfosalicylic acid or heat and acetic acid precipitation, has not existed for at least a decade.

As I recall, an astute participant noted that dipsticks are maximally sensitive for albumin but might fail to detect immunoglobulins or immunoglobulin light chains. Thus, if one had a urine sample with small amounts of light chains and no albumin, the dipstick would be negative and therefore not subject to acid precipitation confirmation of positives. In such a situation, confirmation of negative (rather than positive) protein dipsticks might make more sense.

Accordingly, the CAP Hematology/Clinical Microscopy Resource Committee recommended deletion of that question, along with other wet-chemistry confirmatory tests. The notion of confirming positive dipsticks, which already have high sensitivity for albumin, is archaic.

Albert Rabinovitch, MD, PhD
Checklist commissioner
CAP Commission on Laboratory Accreditation

Q.  We count body fluid WBC using a hemocytometer, and when the result is 0/µL, we report it as zero and do nothing else. My question is, If when counting body fluid WBC using a hemocytometer the result is 0 WBC/µL, do we have to concentrate the specimen using a cytospin and perform a differential? If the answer is yes, then what is the best explanation to give to the physicians questioning the result? For example, where does your differential come from if you reported a zero WBC count? I know that zero is per microliter and not an absolute zero, but it is confusing for the caregivers reading the report.

A.  Your questions raise several points. The first has to do with how to report a "zero" result from a hemocytometer examination. I have surveyed other members of the CAP Hematology/Clinical Microscopy Resource Committee, and a variety of methods are used, including "zero," "none seen," and "<10 cells/µL."

In regards to a subsequent differential, most go ahead and perform one and haven't received queries concerning this discrepancy. Many, however, will prepare a cytospin and only do a differential if cells are present.

I feel it is important to prepare and review this cytospin regardless of a zero count because the cytospin usually represents a concentrated specimen, and the chance of identifying rare abnormal cells is increased, such as in patients with central nervous system involvement by leukemia or lymphoma.

I think any combination of these approaches is acceptable; each institution should decide which method best serves its unique patient population and practice setting.

Katherine A. Galagan, MD
Department of Pathology
Virginia Mason Medical Center

Chair, CAP Hematology/Clinical
Microscopy Resource Committee

Q.  What is the rationale for performing a glucose tolerance test when a patient's fasting blood sugar is high (for example, 160 mg/dL)? The laboratory's policy is to stop the tolerance, but one of our physicians insists on proceeding with the tolerance until a one-hour sample is obtained. He uses this level to determine the amount of insulin his patient should take.

A.  There is no American Diabetes Association recommendation to use the oral glucose tolerance test for diabetes monitoring. The OGTT can be used to diagnose hyperglycemia. There are three conditions under which hyperglycemia is diagnosed: the random plasma glucose is 200 mg/dL or greater in a subject with symptoms of diabetes; the fasting plasma glucose is 126 mg/dL or greater; and a two-hour plasma glucose on OGTT is 200 mg/dL or greater. In the absence of diabetic ketoacidosis or hyperglycemic nonketotic coma at the time of initial presentation, hyperglycemia must be confirmed on two separate occasions to diagnose diabetes. The ADA in 1997 revised the recommended protocol for the OGTT to include only two time points: fasting and two hours. Thus, there is no apparent basis to recommend a one-hour OGTT time point to assess glycemic control. Furthermore, during oral glucose tolerance testing for the diagnosis of diabetes, if the fasting plasma glucose is 126 mg/dL or greater, the OGTT need not be continued because no additional diagnostic information is gained if the two-hour plasma glucose level is elevated (for example, ≥200 mg/dL) in addition to an elevated fasting plasma glucose level (≥126 mg/dL).

There is considerable controversy over whether postprandial self-monitoring of blood glucose should be recommended routinely. This may be the physician's true interest in requesting a one-hour postglucose challenge plasma glucose level. In 2001, the American College of Endocrinology (which is part of the American Association of Clinical Endocrinologists) recommended that, in subjects with diabetes, postprandial glucose be maintained at a level of less than 140 mg/dL. Data suggestive of an association between postprandial hyperglycemia and cardiovascular disease are part of the basis for this recommendation. 1 In a 1997 study, postlunch plasma glucose and "extended postlunch" plasma glucose correlated better with hemoglobin A 1c than fasting plasma glucose. 2

The current ADA recommendations for self-monitoring of blood glucose do not include postprandial targets. A recent review article on the topic of postprandial glucose monitoring 3 found that (1) there was insufficient data to determine the relative contributions of fasting hyperglycemia versus postprandial hyperglycemia on hemoglobin A 1c levels; (2) no data were available that demonstrated a beneficial effect on cardiovascular disease outcome if postprandial glucose was specifically or selectively lowered; and (3) other than in diabetic pregnancies, there were no data demonstrating that lowering postprandial glucose specifically improves outcomes. For instance, in the Insulin Resistance Atherosclerosis Study, impaired glucose tolerance—for example, two-hour OGTT glucose levels of 140-199 mg/dL—was not associated with carotid wall thickness. 4 It can be argued that postprandial hyperglycemia will be minimal in patients with preprandial glucose levels that are at target levels (for example, 80-120 mg/dL). Should postprandial glucose measurements eventually prove to be of significant value in guiding therapy in type 2 diabetes, the use of repaglinide, nateglinide, acarbose, and miglitol might be expanded because these drugs are particularly beneficial in controlling postprandial hyperglycemia.

If the physician wants to assess postprandial glucose levels, this can be accomplished best through self-monitoring of blood glucose after a routine meal. An OGTT cannot be recommended for this purpose. The OGTT tests glycemic responses solely to glucose challenges, whereas ordinary meals provide a mixture of caloric sources as challenges. Furthermore, self-monitoring is much less expensive than an OGTT. The value of measuring fasting or random glucose levels in central laboratories as part of routine diabetes management is minimal in light of the information provided by self-monitoring.

1.  Tominaga M, Eguchi H, Manaka H, et al. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study. Diabetes Care. 1999; 22(6): 920-924.
2.  Avignon A, Radauceanu A, Monnier L. Nonfasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes. Diabetes Care. 1997; 20(12):1822-1826.
3.  Postprandial blood glucose. American Diabetes Association. Diabetes Care. 2001; 24(4): 775-778.
4.  Wagenknecht LE, D'Agostino RB Jr, Haffner SM, et al. Impaired glucose tolerance, type 2 diabetes, and carotid wall thickness: the Insulin Resistance Atherosclerosis Study. Diabetes Care. 1998; 21(11): 1812-1818.

William E. Winter, MD
Department of Pathology
University of Florida

Member, CAP Therapeutic Drug Monitoring
Endocrinology Resource Committee