"In the hospital laboratory, we see specimens sent for hCG
testing there from 80-year-old women, from women with
hysterectomies, and women who are many months
pregnant. Our data indicates that we need to be certain that
the devices we choose can recognize the hCG variants
present in the patient population that we're going to be
testing. As a result of our findings, our hospital switched
their qualitative point-of-care hCG device to a different
brand.
Host: So in your opinion, how can a hospital laboratory or
physician's office using point-of-care hCG devices be certain
that the device they use recognizes the necessary hCG
variants?
Dr. Ann Gronowski: This is an important question. Publications by David
Grenache’s group have utilized the new purified
International Reference Reagents to characterize several of
the hospital point-of-care hCG devices, and our own group
has used this material to characterize several over-thecounter
home use hCG devices.
These types of reports can help professionals select their
qualitative devices. If only early pregnancy urine is going to
be tested, as in a fertility clinic, then any device that
recognizes intact hCG is likely sufficient.
However, if the device is going to be used for more
advanced pregnancies, as in a hospital setting, then a device
that recognizes variants such as free-beta hCG and betacore
fragment should be selected. What's really needed is
for manufacturers to better characterize what hCG variants
their device recognize and to make that information
available. To date that type of research has not been done.
When a negative result is suspected to be a false-negative,
a simple dilution can be performed. The idea here is that as
with the hook effect, you can get the variant antigen down
to a concentration that does not block all the antibodies, and
then a sandwich can form with the intact hCG.
Host: What about quantitative hCG tests? Are they also prone to
this type of problem?
Dr. Ann Gronowski: In theory, yes. Quantitative hCG tests are also potentially
subject to interference with high concentrations of certain
hCG variants. Currently, our laboratory is actually examining
this. hCG beta-core fragment is found almost exclusively in
the urine and currently most quantitative hCG devices are
FDA approved for use with serum only, therefore, there
should be less of a problem with serum quantitative hCG
assays. However, many laboratories have validated their
© 2009 American Association for Clinical Chemistry Page 4 of 4
_____________________________________________________
False-Negative Results in Qualitative hCG Devices
Due to Excess hCG Beta Core Fragment
_____________________________________________________
quantitative devices for use with urine to help when
interpreting difficult cases.
In the August 2009 issue of Clinical Chemistry, Catherine
Sturgeon and colleagues examined the ability of 16 different
quantitative hCG assays to recognize four of the purified
International Reference Reagent variants. Their report
shows clearly that certain quantitative tests just don't
recognize certain hCG variants.
This type of study will be key to interpreting discrepant hCG
results and choosing hCG test for different clinical needs.
We've written an editorial discussing this important work
that appears in the same August issue of Clinical Chemistry.
Host: Well, it seems these data demonstrates that there is just a
lot we still don't know about hCG testing?
Dr. Ann Gronowski: Absolutely. I think that our finding should be a call to arms
for laboratorians to demand better standardization of hCG
immunoassays, and at the very least, better characterization
by manufacturers. We need to know which hCG variants
each device recognizes, and if they're subject to interference
with normal concentrations of hCG variants. Also, we need
to have more discussion and research into what
characteristics different hCG immunoassays should ideally
have.
For example, what hCG variant should be recognized, and
should all variants be recognized by all assays. We've got a
long way to go in the improvement of hCG assays."
Host: Dr. Ann Gronowski is an Associate Professor in the
Departments of Pathology and Immunology and Obstetrics
and Gynecology......
There you have it.
testing there from 80-year-old women, from women with
hysterectomies, and women who are many months
pregnant. Our data indicates that we need to be certain that
the devices we choose can recognize the hCG variants
present in the patient population that we're going to be
testing. As a result of our findings, our hospital switched
their qualitative point-of-care hCG device to a different
brand.
Host: So in your opinion, how can a hospital laboratory or
physician's office using point-of-care hCG devices be certain
that the device they use recognizes the necessary hCG
variants?
Dr. Ann Gronowski: This is an important question. Publications by David
Grenache’s group have utilized the new purified
International Reference Reagents to characterize several of
the hospital point-of-care hCG devices, and our own group
has used this material to characterize several over-thecounter
home use hCG devices.
These types of reports can help professionals select their
qualitative devices. If only early pregnancy urine is going to
be tested, as in a fertility clinic, then any device that
recognizes intact hCG is likely sufficient.
However, if the device is going to be used for more
advanced pregnancies, as in a hospital setting, then a device
that recognizes variants such as free-beta hCG and betacore
fragment should be selected. What's really needed is
for manufacturers to better characterize what hCG variants
their device recognize and to make that information
available. To date that type of research has not been done.
When a negative result is suspected to be a false-negative,
a simple dilution can be performed. The idea here is that as
with the hook effect, you can get the variant antigen down
to a concentration that does not block all the antibodies, and
then a sandwich can form with the intact hCG.
Host: What about quantitative hCG tests? Are they also prone to
this type of problem?
Dr. Ann Gronowski: In theory, yes. Quantitative hCG tests are also potentially
subject to interference with high concentrations of certain
hCG variants. Currently, our laboratory is actually examining
this. hCG beta-core fragment is found almost exclusively in
the urine and currently most quantitative hCG devices are
FDA approved for use with serum only, therefore, there
should be less of a problem with serum quantitative hCG
assays. However, many laboratories have validated their
© 2009 American Association for Clinical Chemistry Page 4 of 4
_____________________________________________________
False-Negative Results in Qualitative hCG Devices
Due to Excess hCG Beta Core Fragment
_____________________________________________________
quantitative devices for use with urine to help when
interpreting difficult cases.
In the August 2009 issue of Clinical Chemistry, Catherine
Sturgeon and colleagues examined the ability of 16 different
quantitative hCG assays to recognize four of the purified
International Reference Reagent variants. Their report
shows clearly that certain quantitative tests just don't
recognize certain hCG variants.
This type of study will be key to interpreting discrepant hCG
results and choosing hCG test for different clinical needs.
We've written an editorial discussing this important work
that appears in the same August issue of Clinical Chemistry.
Host: Well, it seems these data demonstrates that there is just a
lot we still don't know about hCG testing?
Dr. Ann Gronowski: Absolutely. I think that our finding should be a call to arms
for laboratorians to demand better standardization of hCG
immunoassays, and at the very least, better characterization
by manufacturers. We need to know which hCG variants
each device recognizes, and if they're subject to interference
with normal concentrations of hCG variants. Also, we need
to have more discussion and research into what
characteristics different hCG immunoassays should ideally
have.
For example, what hCG variant should be recognized, and
should all variants be recognized by all assays. We've got a
long way to go in the improvement of hCG assays."
Host: Dr. Ann Gronowski is an Associate Professor in the
Departments of Pathology and Immunology and Obstetrics
and Gynecology......
There you have it.
