Q. Does the CAP still require checking positive urine
proteins with sulfo-salicylic acid? I cannot find this in the current
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
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
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
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
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.
In a 1997 study, postlunch plasma glucose and "extended postlunch"
plasma glucose correlated better with hemoglobin A
than fasting plasma glucose.
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
found that (1) there was insufficient data to determine the relative
contributions of fasting hyperglycemia versus postprandial hyperglycemia
on hemoglobin A
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.
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