1. Hoffman R, Benz E, Jr, Shattil S, et al. Hematology: Basic Principles and Practice. London, England: Chruchill Livingstone; 2009. pp. 645–57.
2. Lodi G, Resca D, Reverberi R. Fatal cold agglutinin-induced haemolytic anaemia: a case report. J Med Case Reports. 2010;4:252.[PMC free article][PubMed]
3. Stefanizzi C, Breccia M, Santopietro M, et al. Unusual association of paroxysmal cold hemoglobinuria as the first sign of disease in myelodysplastic patient. Int J Hematol. 2009;89(5):720–1.[PubMed]
4. Dhouib N, Guedhami H, Mellouli F, et al. Mycoplasma pneumoniae associated with severe autoimmune hemolytic anemia in a child with homozygous beta-thalassemia. Tunis Med. 2011;89(7):652–3.[PubMed]
5. Patel M, Durao H, Govender Y. Paroxysmal cold haemoglobinuria coexisting with cold agglutinins in a patient with syphilis resulting in peripheral gangrene: a case report. East Afr Med J. 1993;70(8):526–7.[PubMed]
6. Yagasaki H, Kato M, Shimizu N, Shichino H, Chin M, Mugishima H. Autoimmune hemolytic anemia and autoimmune neutropenia in a child with erythroblastopenia of childhood (TEC) caused by human herpesvirus-6 (HHV-6) Ann Hematol. 2011;90(7):851–2.[PubMed]
7. Arai A, Imadome K, Fujiwara S, Miura O. Autoimmune hemolytic anemia accompanied by reactivation of an Epstein-Barr virus infection with suppressed CTL response to EBV-infected cells in an elderly man. Intern Med. 2010;49(4):325–9.[PubMed]
8. Rheingold SR, Burnham JM, Rutstein R, Manno CS. HIV infection presenting as severe autoimmune hemolytic anemia with disseminated intravascular coagulation in an infant. J Pediatr Hematol Oncol. 2004;26(1):9–12.[PubMed]
9. Khawaja S, Abdul Muqtadir K, Taj Y. Warm autoimmune haemolytic anaemia and autoimmune hepatitis in an asymptomatic carrier of hepatitis B virus. J Pak Med Assoc. 2011;61(5):512–5.[PubMed]
10. Dacie JV, Worlledge SM. Auto-immune hemolytic anemias. Prog Hematol. 1969;6:82–120.[PubMed]
11. Petz LD, Garratty G. Acquired Immune Hemolytic Anemias. 2nd edition. New York, NY: Churchill Livingstone; 2004.
12. Chaplin H, Nasongkla M, Monroe MC. Quantitation of red blood cell-bound C3d in normal subjects and random hospitalized patients. Br J Haematol. 1981;48(1):69–78.[PubMed]
13. Chaudhary R, Das SS, Gupta R, Khetan D. Application of flow cytometry in detection of red-cell-bound IgG in Coombs-negative AIHA. Hematology. 2006;11(4):295–300.[PubMed]
14. Shvidel L, Shtalrid M, Duek A, Haran M, Berrebi A, Sigler E. Direct antiglobulin test reactive with complement only in warm type autoimmune hemolytic anemia. Int J Lab Hematol. 2008;30(6):494–8.[PubMed]
15. Domen RE. Warm red blood cell autoantibodies and the direct antiglobulin test revisited. Am J Clin Pathol. 2004;122(5):673–4.[PubMed]
16. Worlledge SM. The interpretation of a positive direct antiglobulin test. Br J Haematol. 1978;39(2):157–62.[PubMed]
17. Eyster ME, Jenkins DE., Jr Erythrocyte coating substances in patients with positive direct antiglobulin reactions. Correlation of gamma-G globulin and complement coating with underlying diseases, overt hemolysis and response to therapy. Am J Med. 1969;46(3):360–71.[PubMed]
A 47-year-old white woman, who was an active smoker, was referred to the emergency department for the recent onset of exertional dyspnea with chest pain. She did not have a remarkable medical history or family history of anemia and received no medications, although she took pain medication occasionally. Her clinical examination revealed pallor and conjunctival jaundice with mild hepatosplenomegaly. She displayed isolated macrocytic (mean corpuscular volume, 125 fL) anemia (hemoglobin, 4.2 g/dL). An elevated automated reticulocyte count (603 × 109/L) was confirmed by supravital staining with brilliant cresyl blue (panel B; many cells display a typical blue-stained reticulum, original magnification ×1000). Hemolysis was confirmed (lactate dehydrogenase, 2866 IU/L; bilirubin, 62 µmol/L; haptoglobin, <0.1 g/L). The direct antiglobulin test (DAT) was originally negative, however, the examination of the blood smear showed numerous spherocytes (panel A; May-Grünwald–Giemsa stain shows sphere-shaped erythrocytes, original magnification ×1000) that looked consistent with autoimmune hemolytic anemia (AIHA) in the absence of a familial hemolysis history. Hence, a new extensive DAT was performed and revealed the presence of erythrocyte-bound immunoglobulin A (IgA) autoantibodies. Additional exploration revealed chronic nonactive hepatitis C. The severe AIHA was treated with corticosteroids, rituximab, azathioprine, and eventually responded to splenectomy.
Such DAT-negative AIHAs remain rare (∼3%-5% of all AHAIs). Warm IgA antibody AIHAs represent 1% to 2% of all warm AIHAs. This case highlights the relevance of careful blood-smear examination, which can avoid costly investigation of unexplained hemolytic anemia.