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Utility of osmotic fragility test.

Q As a cost-containment and labor-reduction effort, our hematopathology department is reviewing our list of tests. We are seeking information regarding the feasibility and cost effectiveness of performing the osmotic fragility test, which is so labor intensive. This test was the gold standard for diagnosing spherocytosis--but with CBC (complete blood count) indices provided from today's automated hematology instruments and a carefully reviewed smear, does this test really provide any additional clinically significant information? Do you have any statistics on how many institutions still offer this test? Your opinion, please, on the rationale to discontinue offering this test.

A A peripheral blood osmotic fragility test has traditionally been considered important in the workup of hereditary spherocytosis (HS). It has a number of problems, however, including a lack of sensitivity and specificity for HS. In fact, when positive, it merely confirms the presence of spherocytes, regardless of the etiology (hereditary or acquired/autoimmune). It can be positive in hereditary elliptocytosis and autoimmune hemolytic anemia. Furthermore, a normal osmotic fragility test does not exclude HS, since 10% to 20% of HS cases are negative for the test. Cell dehydration of spherocytes in an HS patient is one of the causes of normal osmotic fragility test. In addition, the test is technically difficult and time-consuming; it gives little information beyond what is learned from the automated hematology instrument and a careful review of the peripheral blood smear.

Current guidelines for HS diagnosis include family history, splenomegaly, abnormal CBC indices [spherocytes identification; increase in MCHC (mean corpuscular hemoglobin concentration)], reticulocytes, and RDW (red cell distribution width); and decrease in Hb (hemoglobin) and MCV (mean cell volume), a negative direct antiglobulin test, increased bilirubin, and reticulocytosis. Most cases of HS have a clear-cut presentation as described above, and do not need additional testing for diagnosis. Additional testing will primarily be helpful in situations where there is an atypical morphology or a lack of family history. There are several different tests available for HS, including the osmotic fragility test, acidified glycerol lysis test, osmotic gradient ektacytometry, hypertonic cryohaemolysis test, and eosin-5-maleimide binding test. Each test offers different sensitivities and specificities and may be helpful in different clinical settings. Clinicians will need to select an appropriate test for atypical HS. Unfortunately, many clinicians, especially those who have been practicing for a long time, continue to believe that the osmotic fragility test is the "gold standard" for HS and are reluctant to stop ordering it.

Although we do not know the overall percentage of laboratories that still offer the test, we do know that many have begun offering it as a send-out test only. Our rationale, therefore, is to attempt to educate the clinicians as to the nonspecific nature of the osmotic fragility test and discontinue it as an in-house test. In those cases where the clinician insists an osmotic fragility test is needed, sending it overnight to a reference laboratory should suffice.

--Kathleen Siechen, MD

--Guang Fan, MD, PhD

Hematology Service

Department of Pathology

Oregon Health and Science University

Portland, OR

Suggested Reading

Bolton-Maggs, PHB et al. Guidelines for the diagnosis and management of hereditary spherocytosis. Br J of Haematology. 2004; 126:455-474.

Daniel M. Baer, MD, is professor emeritus of laboratory medicine at Oregon Health and Science University in Portland, OR, and a member of MLO's editorial advisory board.

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Title Annotation:answering your questions; hematopathology department management
Author:Baer, Daniel M.
Publication:Medical Laboratory Observer
Geographic Code:1USA
Date:Sep 1, 2006
Words:554
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