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Innovations in Pathology: Improving laboratory use

The following suggestions for improving laboratory use are from "Lab Tips: A Quarterly Newsletter Helping to Promote Cost-Effective Lab Utilization." It is written by Roger Baxter, MD, under the imprimatur of the Laboratory Utilization Committee of The Permanente Medical Group, of which he is chairman. The success of laboratory utilization projects depends on the cooperation and contributions of various chiefs of departments at the Kaiser Permanente medical centers. Arnold Yee, analyst and administrative liaison, provides and organizes essential utilization data by facility and by individual practitioner.

Medical statistics 101 for clinicians

Clinicians who order tests should remember that each test has certain characteristics related to how the result should be interpreted. Two of these characteristics are "sensitivity" (that is, screening—how well a test picks up every case of disease) and "specificity" (how well the test excludes those who don't have disease).

After you have the results of a test, how sure can you be the patient does or does not have disease? How much can you rely on the test results? For the answer we look to Bayes' theorem, the basis for what follows:

The results of a test must always be interpreted in the context of the population you are testing. This means that your suspicion of disease actually influences the interpretation of the test. Suspicion of disease is called "pretest probability," as opposed to "posttest probability," which is the suspicion of disease after you have the test results. This is statistically measured as the "predictive value" of a positive or negative test, which is a measure of the test's reliability.

Basically, the predictive value of a test takes the specificity, sensitivity, and pretest probability into account and comes up with a value. Here are the formulas from which you can derive these values.

True positive (TP) tests mean the test is positive and the person actually has disease.

False positives (FP) mean the test is positive but the person does not have disease.

True negatives (TN) mean the test is negative and there is no disease.

Predictive value
of a positive test

(Predictive value of a positive is the percent of all positive tests that are true positives.)

(Predictive value of a negative is the percent of all negative tests that are truly negative.)

Let's try some examples—first using a test to screen a population.

The ANA is a test for systemic lupus. Our current assay has a 94 percent sensitivity and 92 percent specificity.

  • Approximately one of every 1,000 young women has lupus, so if we decided to screen 1,000 young women for lupus, we would expect one to have disease.
  • The test is 94 percent sensitive, so we would expect 94 percent x 1 = 0.94 true positive tests.
  • The test is 92 percent specific, so we would expect eight percent of all tests (8% x 1,000) = 80 false-positive tests.
The predictive value of a positive test is 0.94/(0.94 + 80) = 0.01 (1%). This means that if we were to use this test for screening, we would expect that 99 percent of positive tests would be false-positive. The predictive value is extremely low, and we cannot rely on the result of the test. Therefore, the ANA makes a poor screening test.

Now, let's say we use the test to confirm our suspicion of lupus. A 45-year-old woman is in our office with a malar rash, pleuritis, and arthralgias. We think she has a 65 percent chance of having an autoimmune disease, so we do the ANA. The test is positive.

  • In 1,000 similar women, 65 percent (650) would have disease. Ninety-four percent of these (611) would be picked up by the test (TP).
  • Eight percent would still be false-positive (0.08 x 1,000 = 80).

Predictive value of the test = 611/(611 + 80) = 88%.

Therefore, when the test is used to confirm a suspected case, you can rely on a positive test.

Good clinicians use the predictive value of test results intuitively every day when they order tests on their patients. As you can see from the example, you can be misled easily by a test result if you forget the nature of tests when ordering. Remember to order the test when you suspect disease. Few tests have the specificity they would need to be good screening tests. In addition to specificity, the test cost must be justified by the test's benefit in the population tested.

Distinguishing the microcytic anemias

This guideline to help distinguish the microcytic anemias has been endorsed by the regional hematology/oncology chiefs of The Permanente Medical Group.

The two most common causes of microcytic anemia (MCV < 80) are iron deficiency or one of the thalassemia syndromes. The distinguishing characteristics are as follows:

  • Onset. Thalassemias are congenital. A previous normal CBC is strong evidence against this. Hemoglobin electrophoresis should not be sent if iron deficiency is suspected.
  • Ratio of MCV/RBC. The decrease in MCV is proportionately greater with iron deficiency than with thalassemia. The Mentzer Index (MCV/RBC) suggests that thalassemia has an MCV/RBC < 13. This is not completely reliable.
  • Platelet count. Iron deficiency and inflammation often stimulate high platelet counts.
  • RDW. Red cell distribution width is a measure of anisocytosis (uniformity of size of red cells). RDW is usually elevated in acquired anemias and normal or low in thalassemias. Peripheral blood smears may also show target cells in thalassemia, or elliptocytes in iron deficiency, in addition to other findings.
  • Ferritin, TIBC. While ferritin is an acute-phase reactant, it is pathognomonic of iron deficiency if < 15, even in the setting of anemia of chronic disease (low TIBC), and suggestive if near that. A ferritin can be ordered first and the TIBC added if needed. The % iron saturation calculation is useless if TIBC is low and should be ignored in that case.
Thalassemia patients can also have iron deficiency and should be treated accordingly.

A therapeutic trial of iron (in patients with low suspicion for malignancy and not severely symptomatic) can produce a remarkable improvement in iron deficiency. This should be of limited duration so as not to obscure a significant reason for blood loss, such as colon cancer. If the trial is successful, be sure you know the etiology of the iron deficiency.

If iron deficiency is demonstrated outside of the setting of known surgical or menstrual losses, or frequent blood donation, a gastroenterologist should be consulted.

Test add-ons

We repeatedly remind clinicians that it is inconsiderate, unnecessary, inefficient, and inconvenient to re-call patients for repeat phlebotomy when they forgot to order a test, or the need for it is based on the results of a recent test. We save blood specimens for at least a week, so we can generally add the tests they need if they simply call the lab.

Stool specimens (O & P)

There is no reason to order "O&P." There are three kinds of laboratory tests for stool parasites:

  • Protozoal screen: This takes the place of "O&P x 3." Order only one; you get a smear and Giardia EIA. This is enough for the vast majority of suspected parasites, when the patient has diarrhea.
  • Protozoal smear only: When Entamoeba histolytica is highly suspected and the original screen is negative, two more smears may pick up E. histolytica.
  • Helminths: This is the "O" of "O&P." Here we examine the stool for the eggs of helminths, looking for organisms like schistosomiasis. This is not a test for diarrhea but for unusual syndromes in travelers and immigrants.

Digital photography

In appreciation of some of the excellent digital photographs William Dito, MD, and others have taken and shown, I finally became a convert. I'd been a non-negotiable film photographer, partially because I've always done it that way, but largely because digital photographs had essentially no legal status as evidence, thanks to the ease with which they can be manipulated. But, as I've found, digital photography's versatility justifies its use in pathology, if only to prepare photomacrographs, photomicrographs, and texts for teaching conferences for which you've been given too short notice to wait for film processing. (The hand surgeons, by definition, take a lot of digital photographs.) I chose the Olympus Camedia C-720 because of the 8¥ optical zoom, excellent macro mode, and three-megapixel sharpness. Why did you choose the one you're using?

Please share the innovative uses you've devised for your digital camera, and you'll get full credit in this column. If you get it to me by Oct. 15, I'll put it into my December column.

PDAs in pathology

Many of us are relative newcomers to the world of personal digital assistants and would appreciate advice from those who have "been there, done that." Which features and PDAs have you found most useful, which would you avoid, and why? Which medical programs have you found most useful, and why? Are the "free" downloadable programs worth the money? Please give us neophytes the benefits of your experience; if you submit it by Oct. 15, you'll see it in my December column.

Please send in one or more of the innovations you've devised to make your department more cost--efficient or your job easier. Please send your ideas in as soon as possible to help ensure the continuation of this column.

I will send you a sheet of Slide Glide in gratitude for your contribution to this column. Slide Glide is Pathco's (650-321-3441) Teflon-coated, adhesive-backed plastic that mounts on your microscope stage to make it more slippery and to provide a white background for you to look at the slide for ink dots or tissue fragments.