Haptoglobin is primarily produced in the liver and is functionally important for binding free hemoglobin from lysed red cells in vivo, preventing its toxic effects. Because haptoglobin levels become depleted in the presence of large amounts of free hemoglobin, decreased haptoglobin is a marker of hemolysis. Despite its ubiquity and importance, a paucity of literature makes testing difficult to interpret. This review highlights the many physiological roles that have been recently elucidated in the literature. Different methodologies have been developed for testing, including spectrophotometry, immunoreactive methods, and gel electrophoresis. These are covered along with their respective advantages and disadvantages. As there is no single gold standard for hemolysis, validation studies must rely on a combination of factors, which are reviewed in this article. Pitfalls and limitations of testing are also addressed. False positives can occur in improper specimen preparations, cirrhosis, elevated estrogen states, and hemodilution. False negatives can occur in hypersplenism and medications such as androgens and corticosteroids. Haptoglobin testing in the setting of inflammation is additionally discussed as interpretation can be difficult in this setting. Given the widespread use of haptoglobin testing, it is vital that clinicians and laboratory staff understand the principles and correct interpretation of this test.

Automated high performance liquid chromatography and Capillary electrophoresis are used to quantitate the proportion of Hemoglobin A 2 (HbA 2 ) in blood samples order to enable screening and diagnosis of carriers of b-thalassemia. Since there is only a very small difference in HbA 2 levels between people who are carriers and people who are not carriers such analyses need to be both precise and accurate. This paper examines the different parameters of such equipment and discusses how they should be assessed.

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Routine laboratories use a hemoglobin H (HbH) screen to detect alpha-thalassemia carriers of fatal hemoglobin Bart's hydrops fetalis. This test is laborious and has sensitivity concerns. A commercial zeta-globin enzyme-linked immunosorbent assay (ELISA) is effective in detecting Southeast Asian (SEA) alpha-thalassemia. We present results of a study of the effectiveness of carrier detection of ELISA and a shortened HbH screen compared with gap polymerase chain reaction. ELISA was superior to the HbH screen for the SEA alpha0-thalassemia trait. The ELISA and H screen were equal for detection of all carriers encountered and combined were more effective than either test alone. A positive zeta-globin ELISA result is diagnostic of SEA alpha-thalassemia, and routine use of the zeta-globin ELISA in combination with a shortened HbH screen will improve the efficacy of prenatal screening for carriers of hemoglobin Bart's hydrops fetalis through improved detection and referral for follow-up DNA testing.

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Eosinophils function primarily as secretory cells and phagocytosis by eosinophils is rarely seen. We describe a case of chronic eosinophilic leukemia (CEL) in a 72-year-old male with a history of previously treated non-Hodgkin's lymphoma (NHL) presenting with erythrophagocytosis by eosinophils and an associated autoimmune hemolytic anemia (AIHA). This patient did not show evidence of relapsed NHL. The patient's blood showed a markedly ele-

To the Editor: Gladstone et al. (July 28 issue) 1 conclude that early infection in an area in India with a high diversity of rotavirus resulted in lower protection against subsequent infection and disease than has been reported elsewhere. Although there was no significant difference in nutritional status between children with and those without five or more infections, 303 of 373 children in the study (81%) were ever malnourished. Possible immune dysfunction related to deficiency of a trace element such as vitamin A in Indian children may have been contributory. 2

Context.—Quantitation of hemoglobin (Hb) A1c and investigation of hemoglobinopathy on the Bio-Rad Variant analyzers require a switch between 2 separate kits that is time consuming and causes errors. Objective.—Evaluation of a new Variant II HbA2/HbA1c Dual kit capable of both Hb A1c quantitation and hemoglobinopathy investigation on a single kit. Design.—We evaluated Hb A1c, Hb A2, and Hb F quantitation for precision, linearity, and correlation with current methodology. We also evaluated detection of Hb variants and correlation of Hb Barts quantitation. Setting.—Hamilton Regional Laboratory Medicine Program, Provincial Hemoglobinopathy Laboratory, St Joseph's Healthcare Site, Hamilton, Ontario. Patients.—Patient blood samples submitted for Hb A1c quantitation or hemoglobinopathy investigation. Main Outcome Measures.—Precision, linearity, linear regression, and reference interval validation. Results.—We provide tables and figures illustrating precision, linearity, linear regression, and quantitation of Hb variants. We validated reference intervals for Hb A1c, Hb A2, and Hb F. Conclusions.—The dual kit provides precise Hb A1c, Hb A2, and Hb F quantitation. The results show good linearity and correlate well with the results of current methods. We detected all clinically important Hb variants and a wide variety of rare variants. The dual kit has several advantages: it eliminates the need for extensive kit switch over; improves utility for newborn screening because of its quantification of Hb Barts; permits quantification of Hb A1c using the β-Thal method; and eliminates the need for separate Hb A2 reference intervals for patients with Hb S because of its accurate quantitation of Hb A2 in the presence of Hb S.