Artefactually Low Hemoglobin A1C in a Patient with Hemolytic Anemia

Gifford Lum, MD


Lab Med. 2010;41(5):267-270. 

In This Article

Abstract and Introduction


Hemoglobin A1C (HbA1C) is widely used for the monitoring and management of diabetes mellitus. Shortened red cell survival may result in artefactually low HbA1C values. In patients with hemoglobin variants or chemically-modified derivatives of hemoglobin, falsely decreased or increased HbA1C results may be found depending on the particular assay method. Although in most such cases, HbA1C can be reported if the appropriate methodology is selected. In diabetic patients with shortened red cell survival and in a small number of patients with certain hemoglobin variants, alternate approaches such as frequent glucose measurements and/or self glucose monitoring and fructosamine should be used to assess glycemic control. In diabetic patients with these conditions, HbA1C as the preferred diagnostic test for diabetes is not valid.


The patient was an 84-year-old male who was admitted to the emergency room in April 2009 with the chief complaint of increased bilateral lower extremity edema, a 34-pound weight gain over the past month, and worsening anemia. The patient stated that his legs had been steadily swelling over the last month although he had been taking Lasix faithfully (20 mg Monday, Wednesday, and Friday). In the emergency room, the patient was in atrial fibrillation but was free of chest pain. He had significant lower extremity edema and was given IV Lasix and diuresed approximately 1 liter overnight.

Past medical history was significant for rate controlled atrial fibrillation, anemia, warm autoantibodies, type II diabetes mellitus treated with oral medication, congestive heart failure, hypertension, chronic venous insufficiency, osteopenia, arthritis, and compression fracture. A physical examination revealed findings consistent with right and left heart failure with elevated B-type natriuretic peptide (BNP) but no evidence of myocardial infarction. The patient was also found to have 4+ lower extremity edema up to the thighs and lower back. In the hospital the patient's congestive heart failure was treated with Lasix therapy (10 mg IV bid) with net diuresis of >2 liters daily.

Table 1 summarizes this patient's principal laboratory findings. The most striking laboratory findings were anemia (RBC count of 2.12 K/cmm, hemoglobin (Hb) of 7.2 g/dL, hematocrit (Hct) of 22.5%) and a significantly low Hemoglobin A1C (HbA1C), performed using an ion exchange high performance liquid chromatography (HPLC) method, of <3.8%, a value consistent with an estimated average glucose of approximately 77 mg/dL. Because of the discrepancy between the patient's HbA1C level of <3.8% and high glucose concentration of 313 mg/dL, a serum fructosamine level was performed, which was elevated (344 μmol/L).

The patient was evaluated for anemia, which included a normal vitamin B12, folate, and iron/total iron binding capacity (Fe/TIBC). This patient's anemia was clinically thought to be hemolytic in nature, a diagnosis supported by an elevated total bilirubin, increased lactate dehydrogenase (LD), decreased haptoglobin, and elevated reticulocyte count. Examination of the peripheral smear showed polychromasia, fragmented and nucleated red cells, and anisocytosis (Image 1) and the presence of spherocytes (Image 2). The patient was treated with hydrocortisone 1000 mg followed by prednisone 60 mg daily.

Image 1.

Peripheral smear showing polychromasia, fragmented and nucleated red cells, and anisocytosis.

Image 2.

Spherocytes in peripheral smear.

The blood bank workup included a positive direct anti-human globin test, and the presence of a warm autoantibody with the relative specificity of anti e with panreactivity to all red cells in the diagnostic panel. The patient was transfused with 3 units of least incompatible red blood cells, and his Hct rose from 22.5% to 31%. He was discharged with a Hb of 11.1 g/dL and a Hct of 33.3% to be followed in the hematology clinic.


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