Is Sample Quality in the Eye of the Beholder?

Here’s a simple experiment to try in your lab: Find a hemolysed sample and separately ask five different medical laboratory scientists to judge the amount of hemolysis present. What you’ll probably find is that “grossly hemolyzed” is most definitely in the eye of the beholder.

Along with hemolysis, lipemia and icterus are determined by judgment calls made by laboratory scientists. Considering that these three interferences make up the bulk of interferences found in patient samples, “eye of the beholder” may not be good enough. Luckily, with most modern chemistry analyzers, it does not have to be.

Most major chemistry analyzers now perform what we like to call “indices”. The HIL (hemolysis, icterus, lipemia) indices are directly measured by the instrument for a given sample. If any of these three interfering substances are present, the instrument will determine both its presence and its concentration. This last point is important also, because some analytes are only affected by a significantly large amount of the interfering substance. Being able to directly measure these interfering substances, allows the instrument to be set to deal with the affected sample in the most appropriate way. It can be set to not analyze those tests affected, or to not report the results on affected tests, or to simply flag the result for footnoting. Computer systems across the interface can likewise be automatically programmed to accept the HIL numbers and respond appropriately.

Analyzers measure the HIL indices in different ways and until recent years, pediatric labs have often been unable to take advantage of analyzer-measured indices. In pediatrics, especially in infant patients, sample volume is often an issue, and so this feature has traditionally been turned off in pediatric labs. However, there are instruments on the market that measure the indices through the pipet tip without using up any sample volume including most of the Ortho Diagnostics analyzers, like the Fusion 5,1 and the 5600. This feature is one of the reasons these instruments are so often found in pediatric labs. In addition, those instruments that use sample volume are now capable of using microliter quantities, like the Siemens Vista or the Roche Cobas 6000.  Utilizing minimal sample volume for this measurement allows the HIL features to be used on these instruments in almost all situations.

Thus the good news is that the sample quality and appropriateness for any given test no longer needs to be in the eye of the beholder.

-Patti Jones

Pain Management Drug Testing

Traditionally, urine drug testing has looked for the presence of drugs that should not be there. You are hoping for a completely negative drug test. Because tests for measuring drugs in urine haven’t always been incredibly accurate at the low end of the measurement range, and interferences from other compounds can cause false positives and negatives, back in the early 1990s the Department of Health and Human Services provided cut-off concentrations for abused drugs that gave the best discrimination between samples that actually contain those compounds and those that don’t. What that means today is that if the concentration of the drug in the sample is higher than the cut-off, that sample is positive for the tested drug. If the concentration is less than the cut-off, the test is negative, whether there is actually any drug present or not.

How is pain management drug testing different? When testing urine samples for drugs for pain management, you are looking for the presence of drugs that SHOULD be there. In essence, you’re hoping for a positive drug test. Controlling pain with medication is a massive industry, but to keep prescribing those drugs, the physician needs proof that the patient is actually taking the medication and not diverting it for sale or use by someone else. Thus pain management drug testing looks for the presence of the specific drug and may actually require a quantitative result rather than a simple positive/negative.

In addition, although the assays used for both types of drug testing may be the same (mass spectrometry or immunoassay), traditional urine drug testing often only includes drugs in the major classes of drugs of abuse. Pain management drug testing must also include specific drugs prescribed therapeutically for pain, like methadone and oxycodone. Thus point-of-care (POC) devices for drugs of abuse drug testing may not be adequate for pain management drug testing.

Here is a list of drugs usually included in POC testing panels:

Drugs of Abuse
Amphetamines
Opiates
Cocaine
Benzodiazepines
Tetrahydrocannabinoids
Barbiturates
Phencyclidine

Pain Management Testing

Amphetamines
Opiates
Cocaine
Benzodiazepines
Tetrahydrocannabinoids
Barbiturates
Phencyclidine
Oxycodone
Methadone
Propoxyphene

-Patti Jones

Cystic Fibrosis Related Diabetes

Cystic fibrosis-related diabetes (CFRD) is a type of diabetes that affects individuals who have Cystic Fibrosis. CFRD is an entity unto itself, having several aspects that make it different from other forms of diabetes.

Cystic Fibrosis (CF) is one of the most common genetic defects among the Caucasian population, and it is a devastating, systemic disease. When CF was first being diagnosed, children with this disorder rarely lived to reach their teens]; now the average life expectancy  of an individual with CF is around 36 years. Still horrifically short, but better. The fact that people with CF are living longer means they acquire other disorders, including a type of diabetes. It has been shown that with increasing age in the CF population there is increasing incidence of diabetes mellitus.  Roughly 20% of adolescents with CF have diabetes and about 50% of adults with CF have CFRD (1).

CFRD is not as straight-forward to diagnose as type 1 and type 2 diabetes, so it’s important for laboratory professionals to be aware of this disease. People with CF who have diabetes may not always have hyperglycemia. Also hemoglobin A1c (Hgb A1c) values, which is a test recommended by the ADA for diagnosing diabetes, may not be elevated in these patients. The oral glucose tolerance test (OGTT) is recommended for diagnosis of CFRD, and yet even these results may be equivocal in CFRD patients (2). Nonetheless, the ADA/CFF guidelines suggest that all CF patients over 10 years of age should be screened yearly for CFRD using the OGTT. In addition, at least one study in the literature has found that when performing an OGTT on CFRD patients, a glucose level at the 1 hr time point correlates best with the patient’s lung function (3). Thus, if your lab performs OGTT on individuals with suspected CFRD, the physician requesting the test may want the glucose value on a one hour time point as well as the standard 2 hour OGTT.

Individuals with CF who get CFRD tend to have weight loss, protein catabolism, worsened lung function and significantly increased mortality compared to CF individuals without diabetes. The increased mortality is directly related to decreased pulmonary function, rather than to the atherosclerotic vascular disease seen in other types of diabetes. Insulin therapy is the recommended therapy for CFRD.

-Patti Jones

References:

  1. Moran A, Brunzell C, Cohen RC, Katz M, Marshall BC, Onady G, Robinson KA, Sabadosa KA, Stecenko A, Slovis B. Clinical care guidelines for cystic fibrosis-related diabetes.  Diabetes care 33(12):2697-2708. 2010.
  2. Rana M, Munns CF, Selvadurai H, Donaghue KC, Craig ME. Cystic fibrosis-related diabetes in children – gaps in the evidence? Nature Reviews: Endocrinology, 6:371-378. July 2010.
  3. Brodsky J, Dougherty S, Makani R, Rubenstein RC, Kelly A. Elevation of 1-hour plasma glucose during oral glucose tolerance testing is associated with worse pulmonary function in cystic fibrosis. Diabetes Care, 34:292-205. 2011.

Estimated Glomerular Filtration Rate (eGFR)

A colleague, upon checking her lab test results after an annual physical, was horrified to discover a flagged eGFR result of 57 ml/min/1.73 m2; even more so after her research indicated this result could mean she had stage 3 chronic kidney disease. She immediately called her primary care physician, who informed her that since her creatinine value hadn’t changed in more than 25 years (it had been 0.9 at 29 years of age and again at 59 years of age), he ignored the eGFR as useless. So what’s the purpose of an eGFR? If physicians are ignoring it, is it necessary and important to report it with every creatinine value?

Chronic kidney disease is an increasingly huge problem facing the American population. According to the the National Kidney Foundation (NKF) Kidney Disease Outcome Quality Initiative (KDOQI) Guidelines more than 4% of the American population suffers from stage 3 chronic kidney disease, with another 3% in stage 2 and 3% in stage 1. It’s well known that renal function decreases with age, and recent estimates suggest that roughly half the US population is over the age of 50. Although creatinine is the most commonly used marker of renal function, it is a remarkably insensitive marker of renal function loss, and new markers are just being discovered and validated. Glomerular Filtration Rate (GFR) is considered the best estimate of kidney function; however it’s not simple to measure.   eGFR is an estimated GFR, calculated from the creatinine the age, gender and race of the patient. It is a way of assisting in the early diagnosis of kidney disease. To help make this diagnosis, urine albumin is an important test to use along with eGFR. In addition, both should be abnormal for >3 months in order to make the diagnosis. Early diagnosis can help prevent progression to renal failure.

The equations for calculating eGFR have evolved and improved, from the early 6-parameter formula which came out of the Modification of Diet in Renal Disease (MDRD) study, to the most recent 4-parameter CKD-EPI formula. For adults, the CKD-EPI formula is increasingly being considered the most useful of these formulas. Formulas are also available for children, and online calculators are easy to find.

Patti Jones