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Year : 2008  |  Volume : 51  |  Issue : 4  |  Page : 571-572
Coomb's negative autoimmune hemolytic anemia: A diagnostic dilemma for the hematologist


Department of Pathology, Maulana Azad Medical College, Bahadurshah Zafar Marg, New Delhi - 110 002, India

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How to cite this article:
Gupta R, Singh DK, Singh S, Singh T. Coomb's negative autoimmune hemolytic anemia: A diagnostic dilemma for the hematologist. Indian J Pathol Microbiol 2008;51:571-2

How to cite this URL:
Gupta R, Singh DK, Singh S, Singh T. Coomb's negative autoimmune hemolytic anemia: A diagnostic dilemma for the hematologist. Indian J Pathol Microbiol [serial online] 2008 [cited 2017 Apr 25];51:571-2. Available from: http://www.ijpmonline.org/text.asp?2008/51/4/571/43771


Sir,

We would like to share our recent experience with a patient diagnosed with Coomb's negative autoimmune hemolytic anemia (AIHA). A 40-year-old female presented with breathlessness, easy fatigability and anorexia for 10 months. She had a history of jaundice 1 month prior to the presentation. There was a history of similar complaints 1 year prior, which remitted without any treatment. There was no history of exposure to chemicals, blood transfusion, drug intake, or known allergies. There was no fever or symptoms suggestive of infection.

On examination, the patient was pale with mild icterus. The spleen tip was palpable; however, there was no hepatomegaly or lymphadenopathy. Investigations revealed a hemoglobin level of 6.1 g/dl, a total leukocyte count of 8100/mm 3 with 74% polymorphs, 25% lymphocytes and 1% eosinophils and a platelet count of 1.6 lac/mm 3 . The erythrocyte sedimentation rate (ESR) was 80 mm in the first hour by Westergren's method. A peripheral smear showed moderate anisocytosis with mild hypochromia, polychromatophils and few microspherocytes. No malarial parasite was seen. There were no bite cells or Heinz bodies. The reticulocyte count with brilliant cresyl blue was 20% and HbH inclusions were absent. Serum bilirubin was raised to 3.0 mg/dl (direct 0.4 mg/dl) with normal liver enzymes. The lactate dehydrogenase level was 2443 U/L and urine was negative for hemosiderinuria. The clinical and hematological features were suggestive of hemolytic anemia and the patient was further investigated for the cause of hemolysis.

Considering the history and hematological findings, hemoglobinopathy, red cell enzyme defect and hereditary ovalocytosis as possible etiologies for hemolytic anemia were excluded. Osmotic fragility showed a tail of fragile cells. A Nile blue reduction test and elution tests for G-6-PD deficiency were negative. Ham's test for paroxysmal nocturnal hemoglobinuria was negative and serology for viral infections (CMV, EBV and Hepatitis A and B) was negative. A normal computerized tomography (CT) scan, negative dsDNA and rheumatoid factor excluded underlying malignant conditions and connective tissue disorders. Direct and indirect Coomb's tests performed with poly-specific antisera at 4 C and 37 C by tube method were negative (repeated twice). The patient could not afford more sensitive methods of direct antiglobulin tests (DAT).

With a presumptive diagnosis of AIHA, the patient was given prednisolone 60 mg/m 2 /day. There was a dramatic improvement with a rise in hemoglobin to 9.2 g/dl and a reduction in reticulocyte count to 7%. There was a concurrent reduction in polychromasia and microspherocytes on the peripheral smear. An attempt to withdraw corticosteroids led to a recurrence of hemolysis, which responded to the reinstitution of steroids at 60 mg/m 2 /day. The patient is currently doing well and is receiving maintenance doses of steroids.

AIHA is a relatively uncommon disorder that occurs due to the presence of IgG or IgM autoantibodies against red cell membrane antigens. The degree of hemolysis varies among patients and depends on the characteristics of the antibody. [1] The cornerstone of diagnosis of AIHA is a positive Coomb's antiglobulin test in a proper clinical setting. [2] The diagnosis of AIHA is usually not seriously considered in the absence of a positive Coomb's test, attesting to the importance given to this procedure. [3] However, gradually reports of Coomb's negative AIHA are being added to English literature.

The exact frequency of Coomb's negative AIHA is not known. [3] Naithani, et al. found six patients who were found to be negative by DAT in their series of 79 cases. [1] In such patients, other causes of hemolysis need to be ruled out using pertinent investigations. Negative DATs in patients with AIHA could be due to low levels of antibodies on red cell membranes or a low sensitivity of conventional tube method of DAT. [4] The sensitivity of DAT may be improved by modifications using polyvinyl pyrrolidone (PVP), bromelin, flow cytometry, enzyme linked DAT, radioimmunoassays using 125 I-labeled anti-IgG or 125 I staphylococcal protein A, solid phase DAT using microtiter plates, gel testing or using mono-specific antisera. [4] In mono-specific DAT, mono-specific anti-IgG, -IgM, -IgA, or anti-C3d antibodies are used. [5] In the developing world, DAT is still being performed by the conventional tube method in most hospitals. This may lead to some cases of AIHA being missed or having a significant delay in diagnosis. The detection of DAT negative AIHA cases is important since AIHA can be a life-threatening condition with intense hemolysis, shock and death. As with DAT-positive AIHA, DAT-negative cases also respond to corticosteroids. Cases of patients with AIHA not responding to steroids or with intolerable side effects of steroids may be offered a splenectomy, immunosuppressive drugs, plasmapheresis, or danazol. [2]

In conclusion, Coomb's negative autoimmune hemolytic anemia needs to be recognized so that an early diagnosis can be made and appropriate therapy can be given. In such cases, sensitivity of Coomb's test may be enhanced using various modifications.

 
   References Top

1.Naithani R, Agarwal N, Mahapatra M, Pati H, Kumar R, Choudhary VP. Autoimmune hemolytic anemia in India: Clinico-hematological spectrum of 79 cases. Hematology 2006;11:73-6.  Back to cited text no. 1    
2.Agarwal B. Autoimmune hemolytic anemia. Indian J Pediatr 1998;65:663-8.  Back to cited text no. 2  [PUBMED]  
3.Gilliland BC. Coomb's negative immune hemolytic anemia. Semin Hematol 1976;13:267-75.  Back to cited text no. 3  [PUBMED]  
4.Engelfriet CP, Overbeeke MA, von D Borne AE. Autoimmune hemolytic anemia. Semin Hematol 1992;29:3-12.  Back to cited text no. 4    
5.Kemppinnen E, Vuopio P, Sandstom R, Wager O. Significance of mono-specific antisera in the diagnosis and prognosis of autoimmune hemolytic anemias. Ann Clin Res 1981;13:85-90.  Back to cited text no. 5    

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Correspondence Address:
Ruchika Gupta
162, Pocket-B, Sarita Vihar, New Delhi - 110 076
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.43771

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