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February 2005
Originally published in CAP TODAY
Stephen J. Sarewitz, MD
Q. Before we do a mixing study on a patient, we always call the floor to make sure the patient is not on any anticoagulant drugs. Why is the CAP now suggesting that we screen these patients for the drugs instead of accepting the information from the nurse or doctor? We do not perform any of the assays the College suggests we perform for heparin.
A. The intent of this question follows the principle
of the mixing studies, which are intended to differentiate coagulation inhibitors—that
is, lupus anticoagulants or factor inhibitors—from factor deficiencies.
But because heparin acts as an immediate-acting coagulation inhibitor, the presence
of heparin in a specimen can give a false impression of a clinically significant
inhibitor. Heparin can be present in the plasma because the patient is receiving
heparin therapy, but heparin is also a common contaminant due to heparin flushes
and heparin in indwelling catheters. Consequently, samples on which mixing studies
are performed should be screened for heparin when positive results are obtained.
This is to avoid erroneously reporting a positive inhibitor when the abnormal
results are due to heparin contamination of the sample. Some laboratories screen
for heparin by performing an anti-Xa heparin assay, while others treat the sample
with polybrene or heparinase to eliminate the heparin effect.
These are only suggestions regarding what a lab can do when the results of the mixing studies are positive. The laboratory could also ask for information from the nursing unit or the physician. However, if a patient is on a catheter, the nurse or doctor may not be aware that the heparin in the catheter may affect the mixing studies. Many laboratories add a disclaimer to positive mixing studies indicating that heparin may affect the results.
Q. I am trying to find the CAP requirement for how often
to run external quality controls on human chorionic gonadotropin qualitative
tests. Is it acceptable to run quality controls on each lot, or do we need to
continue doing them daily?
A. The guideline regarding the use of built-in
controls is listed in most of the checklists, which can be viewed on the CAP
Web site, www.cap.org.
Immunology checklist item IMM.34325, for example, states: For tests that do include built-in positive and negative controls, is a positive and negative external control tested with each new kit lot number or different shipment of a given lot number for all qualitative or semi-quantitative antigen-antibody tests (e.g., rheumatoid factor, rapid plasma reagin, ASO, hCG, heterophile antibody, etc.)?
If the manufacturer states that the product has a built-in positive and negative control, and the medical director accepts the internal controls as appropriate for daily quality control, this is acceptable. For qualitative testing, known positive and negative controls must be documented with each run of patient testing. A run can be defined as the interval in which the test system is expected to be stable (based on the manufacturer's recommendations) but at least each 24 hours that patient testing is performed. This, historically, has been accomplished by running positive and negative liquid (external) controls. The use of positive and negative internal controls may be acceptable for use with test systems that have been classified as waived or moderate complexity under CLIA '88 and have not been modified. The laboratory director is responsible for approving the QC process established in the laboratory.
External quality control is required at the change of lot number or shipment, or both. Based on the performance of the quality control system in place, the medical director may determine whether or not it is necessary to run additional quality control.
Q. I understand that the new point-of-care testing checklist will not be available until March. Is there any way we can know how the CAP intends to interpret the new CLIA regulations for equivalent QC? Specifically, will we be required to perform verification and monthly liquid QC on every instrument when multiple same analyzers are used in the facility (i-Stat, for example), or can we use a representative number of handhelds?
A. The CAP Laboratory Accreditation Program and
the CAP's scientific resource committees are reviewing the draft state operations
manual that addresses the CLIA regulations on equivalent QC standards. After
this information is reviewed, the College will incorporate changes in its checklist
requirements if appropriate. Until changes are approved and incorporated, please
continue to follow the requirements of the current checklists. (The new edition
of the point-of-care checklist should be available in 2005, but probably not
as early as March.)
POC checklist items POC.08500 and POC. 08700 give a detailed description of acceptable options for analytical measurement range validation and multi-instrument comparison. In summary, once the AMR has been established initially for each device and it has been determined that all the POC equipment correlates by using patient samples, it is acceptable to use a combination of methods for validating the AMR and performing multi-instrument comparisons every six months.
As a means for compliance with the abovementioned checklist items, you would initially establish the AMR on all the glucose meters or i-Stat instruments. Linearity is a common method to establish AMR. Follow the manufacturer's guidelines regarding the number of samples and replicates needed.
Linearity is not a CAP requirement; however, it is most commonly used to establish
the analytical measurement range at initial setup of each instrument. AMR validation
is then required every six months by testing three levels of material (calibrators,
linearity material) that span the AMR. The CAP does not specify a required number
of samples; that is a determination for the laboratory to make. You should attempt
to cover the entire analytical measurement range. Within 10 percent of the top
of the AMR and 50 percent of the lower AMR limit are goals to aim for. For some
analytes, these guidelines will be difficult to achieve, and the laboratory
director needs to determine low and high values that will validate acceptable
clinical performance of the test.
Continued acceptable device performance is based on validating the AMR for representative device(s) every six months and for the other devices by consistent QC results that meet the established acceptability values. The definition of a representative number would be at the discretion of your medical director. Continued acceptable performance can also be documented by monitoring the agreement between results from the POC tests and near-simultaneously collected blood sent to the laboratory for analysis. This approach can also concurrently document correlation between devices and the main laboratory method (POC.08700).
The following references may be resources in establishing the comparisons:
Clinical and Laboratory Standards Institute (formerly NCCLS)Guideline EP9-A,
"Method Comparison and Bias Estimation Using Patient Samples" (www.clsi.org)
and the CAP's 1999 publication, Laboratory Instrument Evaluation, Verification
and Maintenance Manual, which can be purchased by calling 847-832-7000
ext. 6515. The Laboratory Instrument Evaluation, Verification and
Maintenance Manual is no longer available from the CAP. The proposed CLSI
standard, GP31-P, Laboratory Instrument Evaluation, Verification and Maintenance
Manual is in development and expected to be available before the end of
2005. Please contact the CLSI, 610-688-0100, for further information.
CLSI document EP9-A is a helpful reference to use for determining the number
of samples that should be tested for correlation.
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