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© American Society for Clinical Pathology<br />

Coagulation and Transfusion Medicine / LABORATORY-INITIATED REFLEX TESTING FOR AIHA<br />

<strong>Au<strong>to</strong>matic</strong> <strong>Labora<strong>to</strong>ry</strong>-<strong>Initiated</strong> <strong>Reflex</strong> <strong>Testing</strong> <strong>to</strong> <strong>Identify</strong><br />

<strong>Patients</strong> With Au<strong>to</strong>immune Hemolytic Anemia<br />

Paul Froom, MD, Alexander Neck, MD, Michaela Shir, MS, Rosa Haavis, and Mira Barak, PhD<br />

Key Words: Normocytic; Anemia; <strong>Labora<strong>to</strong>ry</strong>; Workup<br />

DOI: 10.1309/CFEECW31UYLHUJQG<br />

Abstract<br />

The clinical usefulness of au<strong>to</strong>matic labora<strong>to</strong>ryinitiated<br />

testing of patients with recent-onset<br />

normocytic anemia <strong>to</strong> diagnose au<strong>to</strong>immune hemolytic<br />

anemia (AIHA) is uncertain. During a 28-month period,<br />

we performed 784,185 CBC counts. <strong>Patients</strong> without a<br />

his<strong>to</strong>ry of anemia had reticulocyte count testing if<br />

hemoglobin values were less than 10 g/dL (


Froom et al / LABORATORY-INITIATED REFLEX TESTING FOR AIHA<br />

abnormal test results are compared with previous results if<br />

present in the database.<br />

In all patients without a his<strong>to</strong>ry of anemia, we performed<br />

a reticulocyte count if the hemoglobin value was less than 10<br />

g/dL (


❚Table 1❚<br />

Univariate Analysis *<br />

led <strong>to</strong> considerable savings by decreasing physician visits.<br />

Cost-effectiveness, however, can be calculated only by determining<br />

the number of additional physician follow-up visits for<br />

patients who are not tested au<strong>to</strong>matically.<br />

Negative consequences of au<strong>to</strong>matic labora<strong>to</strong>ry testing<br />

include redundant testing in approximately 20% of the<br />

patients with a positive direct antiglobulin test result, with previous<br />

positive test results in the hospital or from other areas in<br />

Israel. This might be prevented by improved computer integration<br />

of test results from other sources. Also, 87.7% of<br />

patients with elevated reticulocyte counts did not have a positive<br />

direct antiglobulin test result, and not all with a positive<br />

direct antiglobulin test result were treated. In these patients,<br />

additional test results outside the reference range could lead <strong>to</strong><br />

negative consequences, including patient anxiety. Also, the<br />

effect of the test results on subsequent testing and treatment in<br />

patients without au<strong>to</strong>immune hemolytic anemia needs <strong>to</strong> be<br />

studied because the added testing might have had positive or<br />

negative effects on patient care.<br />

We were unable <strong>to</strong> find clinical or CBC count variables<br />

that aid in limiting direct antiglobulin testing. Neither<br />

absolute reticulocyte counts nor corrected absolute reticulocyte<br />

counts were better than the more familiar uncorrected<br />

reticulocyte test.<br />

The cu<strong>to</strong>ff for the degree of anemia needed <strong>to</strong> initiate a<br />

reticulocyte count is uncertain. It is possible that patients with<br />

a hemoglobin value of 10 g/dL (100 g/L) or more also might<br />

benefit from such testing. Further studies are warranted <strong>to</strong><br />

substantiate our findings and <strong>to</strong> determine the proper cu<strong>to</strong>ff<br />

for au<strong>to</strong>matic direct antiglobulin testing.<br />

Extrapolation of our results <strong>to</strong> other settings should be<br />

done with caution. The upper end of the reference interval for<br />

reticulocytes in our labora<strong>to</strong>ry is 1.9% (0.019) but has been<br />

reported variously <strong>to</strong> be 2.7% (0.027), 3 1.8% (0.018), 3 1.6%<br />

(0.016), 4 1.25% (0.013), 5 2.16% (0.022), 6 1.79% (0.018), 6<br />

1.55% (0.016), 6 2.24% (0.022), 6 1.44% (0.014), 6 1.85%<br />

(0.019), 7 2.3% (0.023), 7 and 1.6% (0.016), 8 depending in<br />

© American Society for Clinical Pathology<br />

Coagulation and Transfusion Medicine / ORIGINAL ARTICLE<br />

Direct Antiglobulin Test Results<br />

Variable Positive (n = 52) Negative (n = 372) P<br />

Age (y) 60 ± 20 52 ± 25 .025<br />

Female 35 (67.3) 244 (65.6) .807<br />

Reticulocyte count, % of RBCs (proportion of RBCs) 6.5 ± 5.5 (0.065 ± 0.055) 4.7 ± 2.7 (0.047 ± 0.027)


Froom et al / LABORATORY-INITIATED REFLEX TESTING FOR AIHA<br />

Conclusion<br />

The labora<strong>to</strong>ry initiation of the workup ensured recommended<br />

medical practices, probably saved physician visits,<br />

and, in some patients, led <strong>to</strong> more timely diagnosis and appropriate<br />

treatment. Our findings support the use of reflex labora<strong>to</strong>ry-initiated<br />

testing in patients with normocytic anemia.<br />

Further studies are warranted <strong>to</strong> determine whether our findings<br />

can be extrapolated <strong>to</strong> other settings.<br />

From the Central <strong>Labora<strong>to</strong>ry</strong> of Haifa and Western Galilee, Clalit<br />

Health Services, Nesher, Israel.<br />

Address reprint requests <strong>to</strong> Dr Froom: Hema<strong>to</strong>logy<br />

Labora<strong>to</strong>ries, Central <strong>Labora<strong>to</strong>ry</strong> of Haifa and Western Galilee,<br />

Clalit Health Services, Nesher, Israel.<br />

References<br />

1. Normocytic normochromic anemias other than hemolytic<br />

anemias. In: Wintrobe MW, Lee GR, Boggs DR, et al, eds.<br />

Clinical Hema<strong>to</strong>logy. 8th ed. Philadelphia, PA: Lea and Febiger;<br />

1981:677-724.<br />

2. Beutler E. Production and destruction of erythrocytes. In:<br />

Beutler E, Lichtman MA, Coller BS, et al, eds. Williams<br />

Hema<strong>to</strong>logy. 6th ed. New York, NY: McGraw-Hill; 2001:356.<br />

3. Van Houte AJ, Bartels PC, Schoorl M, et al. Methodologydependent<br />

variations in reticulocyte counts using a manual<br />

and two different flow cy<strong>to</strong>metric procedures. Eur J Clin Chem<br />

Clin Biochem. 1994;32:859-863.<br />

132 Am J Clin Pathol 2005;124:129-132<br />

132 DOI: 10.1309/CFEECW31UYLHUJQG<br />

4. Nobes PR, Carter AB. Reticulocyte counting using flow<br />

cy<strong>to</strong>metry. J Clin Pathol. 1990;43:675-678.<br />

5. Kojima K, Niri M, Se<strong>to</strong>guchi K, et al. An au<strong>to</strong>mated<br />

op<strong>to</strong>electronic reticulocyte counter. Am J Clin Pathol.<br />

1989;92:57-61.<br />

6. Van den Bossche J, Devreese K, Malfait R, et al. Reference<br />

intervals for a complete blood count determined on different<br />

au<strong>to</strong>mated haema<strong>to</strong>logy analyzers: Abx Pentra 120 Retic,<br />

Coulter Gen-S, Sysmex SE 9500, Abbott Cell Dyn 4000, and<br />

Bayer Advia 120. Clin Chem Lab Med. 2002;40:69-73.<br />

7. Buttarello M, Bulian F, Venudo A, et al. <strong>Labora<strong>to</strong>ry</strong> evaluation<br />

of the Miles H.3 au<strong>to</strong>mated reticulocyte counter: a<br />

comparative study with manual reference method and Sysmex<br />

R-1000. Arch Pathol Lab Med. 1995;119:1141-1148.<br />

8. Nobes PR, Carter AB. Reticulocyte counting using flow<br />

cy<strong>to</strong>metry. J Clin Pathol. 1990;43:675-678.<br />

9. Hegde UM, Gordon-Smith EDC, Worlledge SM.<br />

Reticulocy<strong>to</strong>penia and absence of red cell au<strong>to</strong> antibodies in<br />

au<strong>to</strong>immune hemolytic anemia: analysis of 109 cases. Br Med<br />

J. 1977;2:1444-1447.<br />

10. Liesveld JL, Rowe JM, Lichtman MA. Variability of the<br />

erythropoietic response in au<strong>to</strong>immune hemolytic anemia.<br />

Blood. 1987;69:820-826.<br />

11. Packman CH. Acquired hemolytic anemia due <strong>to</strong> warmreacting<br />

au<strong>to</strong>antibodies. In Beutler E, Lichtman MA, Coller<br />

BS, et al, eds. Williams Hema<strong>to</strong>logy. 6th ed. New York, NY:<br />

McGraw-Hill; 2001:641.<br />

© American Society for Clinical Pathology

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