The Clinical Pictures of Autoimmune Hemolytic Anemia

Charles H Packman, Charles H Packman

Abstract

Autoimmune hemolytic anemia is characterized by shortened red blood cell survival and a positive Coombs test. The responsible autoantibodies may be either warm reactive or cold reactive. The rate of hemolysis and the severity of the anemia may vary from mild to severe and life-threatening. Diagnosis is made in the laboratory by the findings of anemia, reticulocytosis, a positive Coombs test, and specific serologic tests. The prognosis is generally good but renal failure and death sometimes occur, especially in cases mediated by drugs.

Keywords: Agglutinin; Autoimmunity; Direct antiglobulin test; Hemolysin; Hemolysis.

Figures

Fig. 1
Fig. 1
Physical examination in warm antibody AIHA. Skin pallor, icterus and nailbed pallor in a patient with treatment-refractory warm AIHA, hemoglobin 4.8 g/dl (photographs courtesy of Professor A. Salama, with kind permission of the patient).
Fig. 2
Fig. 2
Physical examination in cold antibody AIHA. a Livedo reticularis (photograph courtesy of Professor A. Salama). b Acrocyanosis involving the toes in a patient with a high-titer IgM cold agglutinin (reprinted from Sinha A, Richardson G, Patel RT : Cold agglutinin related acrocyanosis and paroxysmal hemolysis. Eur J Vasc Endovasc Surg, 30:563-565, copyright 2005, with permission from Elsevier).
Fig. 3
Fig. 3
Blood films from patients with AIHA. Used with permission from Lichtman's Atlas of Hematology, www.accessmedicine.com. a Cold agglutinin disease, low power, slide made at room temperature. Note agglutination of RBCs. b Warm antibody AIHA. Note frequent small, round RBCs lacking central pallor, large bluish RBCs (polychromasia), Howell-Jolly body and nucleated RBCs.

References

    1. Packman CH. Hemolytic anemia resulting from immune injury; in Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW, Burns LJ, Caligiuri MA (eds): Williams Hematology, 9th ed. New York, McGraw-Hill, chapter 54, 2016 (in press).
    1. Dacie JV. The Haemolytic Anaemias, vol 3, The Autoimmune Haemolytic Anaemias, 3rd ed. New York, Churchill Livingstone, 1992.
    1. Petz LD, Garratty G. Acquired Immune Hemolytic Anemias. Philadelphia, Churchill Livingstone, 2004.
    1. Sokol RJ, Hewitt S, Stamps BK. Autoimmune haemolysis: an 18 year study of 865 cases referred to a regional transfusion centre. Br Med J. 1981;282:2023–2027.
    1. Mayer B, Yürek S, Kiesewetter H, Salama A. Mixed‐type autoimmune hemolytic anemia: differential diagnosis and a critical review of reported cases. Transfusion. 2008;48:2229–2234.
    1. Shulman IA, Branch DR, Nelson JM, Thompson JC, Saxena S, Petz LD. Autoimmune hemolytic anemias with both cold and warm autoantibodies. JAMA. 1985;253:1746–1748.
    1. Salama A, Mueller-Eckhardt C. On the mechanisms of sensitization and attachment of antibodies to RBCs in drug-induced immune hemolytic anemia. Blood. 1987;69:1006–1010.
    1. Berentsen S, Bo K, Shammas F, Myking A, Ulvestad D. Chronic cold agglutinin disease of the ‘idiopathic’ type is a premalignant or low-grade malignant lymphoproliferative disease. APMIS. 1997;105:354–362.
    1. Jacobson LB, Longstreth GF, Edington TS. Clinical and immunologic features of transient cold agglutinin hemolytic anemia. Am J Med. 1973;54:514–521.
    1. Worlledge SM, Dacie JV. Haemolytic and other anaemias in infectious mononucleosis; in Carter RL, Penman HG (eds): Infectious Mononucleosis. Oxford, Blackwell Science, 1969, p 82.
    1. Gottsche B, Salama A, Mueller-Eckhardt C. Donath-Landsteiner autoimmune hemolytic anemia in children: a study of 22 cases. Vox Sang. 1990;58:281–286.
    1. Nordhagen R, Stensvold K, Winsnes A, Skyberg D, Storen A. Paroxysmal cold hemoglobinuria. The most frequent autoimmune hemolytic anemia in children? Acta Paediatr Scand. 1984;73:258–262.
    1. Arndt PA, Garratty G. Cross-reactivity of cefotetan and ceftriaxone antibodies, associated with hemolytic anemia, with other cephalosporins and penicillin. Coagul Transfusion Med. 2002;118:256–262.
    1. Garratty G, Nance S, Lloyd M, Domen R. Fatal immune hemolytic anemia due to cefotetan. Transfusion. 1992;32:269–271.
    1. Habibi B, Basty R, Chodez S, Prunat A. Thiopental- related immune hemolytic anemia and renal failure. N Engl J Med. 1985;312:353–355.
    1. Garratty G, Postoway N, Schwellenbach J, McMahill PC. A fatal case of ceftriaxone (Rocephin)-induced hemolytic anemia associated with intravascular immune hemolysis. Transfusion. 1991;31:176–179.
    1. Evans RS, Duane RT. Acquired hemolytic anemia: I. The relation of erythrocyte antibody production to activity of the disease: II. The significance of thrombocytopenia and leukopenia. Blood. 1949;4:1196–1213.
    1. Liesveld JL, Rowe JM, Lichtman MA. Variability of the erythropoietic response in autoimmune hemolytic anemia: analysis of 109 cases. Blood. 1987;69:820–826.
    1. Conley CL, Lippman SM, Ness P. Autoimmune hemolytic anemia with reticulocytopenia: a medical emergency. JAMA. 1980;244:1688–1690.
    1. Engelfriet CP, von dem Borne AE, Beckers D, van Loghem JJ. Autoimmune haemolytic anaemia: serological and immunochemical characteristics of the autoantibodies: mechanisms of cell destruction. Ser Haematol. 1974;7:328–347.
    1. Wolf CF, Wolf DJ, Peterson P, Brandstetter RD, Hansen DE. Autoimmune hemolytic anemia with predominance of IgA autoantibody. Transfusion. 1982;22:238–240.
    1. Szymanski IO, Teno R, Rybak ME. Hemolytic anemia due to a mixture of low-titer IgG lambda and IgM lambda agglutinins reacting optimally at 22 degrees C. Vox Sang. 1986;51:112–116.
    1. Göttsche B, Salama A, Mueller-Eckhardt C. Autoimmune hemolytic anemia associated with an IgA autoanti-Gerbich. Vox Sang. 1990;58:211–214.
    1. Evans RS, Bingham M, Boehni P. Autoimmune hemolytic disease: antibody dissociation and activity. Arch Intern Med. 1961;108:338–352.
    1. Gilliland BC, Leddy JP, Vaughan JH. The detection of cell-bound antibody on complement-coated human red cells. J Clin Invest. 1970;49:898–906.
    1. Segel GB, Lichtman MA. Direct antiglobulin (‘Coombs') test-negative autoimmune hemolytic anemia: A review. Blood Cells Mol Dis. 2014;52:152–160.
    1. Sokol RJ, Hewitt S, Booker DJ, Bailey A. Erythrocyte autoantibodies, subclasses of IgG and autoimmune haemolysis. Autoimmunity. 1990;6:99–104.
    1. von dem Borne AE, Beckers D, van der Meulen W, Engelfriet CP. IgG4 autoantibodies against erythrocytes, without increased hemolysis: a case report. Br J Haematol. 1977;37:137–144.
    1. Issitt PD, Pavone BG, Goldfinger D, Zwixker H, Issitt CH, Tessel JA, Kroovand SW, Bell CA. Anti-Wrb and other autoantibodies responsible for positive direct antiglobulin test in 150 individuals. Br J Haematol. 1976;34:5–17.
    1. Weiner W, Vos GH. Serology of acquired hemolytic anemia. Blood. 1963;22:606–613.
    1. Vos GH, Petz L, Funenberg HH. Specificity of acquired haemolytic anaemia autoantibodies and their serological characteristics. Br J Haematol. 1970;19:57–66.
    1. Leddy JP, Peterson P, Yeaw MA, Bakemeier RF. Patterns of serologic specificity of human γ G erythrocyte autoantibodies. J Immunol. 1970;105:677–686.
    1. Leddy JP, Falany JL, Kissel GE, Passodor, ST, Rosenfeld SI. Erythrocyte membrane proteins reactive with human (warm-reacting) anti-red cell autoantibodies. J Clin Invest. 1993;91:1672–1680.
    1. Bell CA, Zwicker H. Further studies on the relationship of anti-Ena and anti-Wrb in warm autoimmune hemolytic anemia. Transfusion. 1978;18:572–575.
    1. Celano MJ, Levine P. Anti-LW specificity in autoimmune acquired hemolytic anemia. Transfusion. 1967;7:265–268.
    1. Marsh WL, Reid ME, Scott EP. Autoantibodies of U blood group specificity in autoimmune haemolytic anaemia. Br J Haematol. 1972;22:625–629.
    1. Shulman IA, Vengelen-Tyler V, Thompson JC, Nelson JM, Chen DC. Autoanti-Ge associated with severe autoimmune hemolytic anemia. Vox Sang. 1990;59:232–234.
    1. Owen I, Chowdhury V, Reid ME, Poole J, Marsh JC, Hows JM. Autoimmune hemolytic anemia associated with anti-Sc 1. Transfusion. 1992;32:173–176.
    1. Marsh WL, Oyen R, Alicea E, Linter M, Horton S. Autoimmune hemolytic anemia and the Kell blood groups. Am J Hematol 1979;155-162.
    1. Roelcke D. Cold agglutination: antibodies and antigens. Clin Immunol Immunopathol. 1974;2:266–280.
    1. Curtis BR, Lamon J, Roelcke D, Chaplin H. Life-threatening, antiglobulin test-negative, acute autoimmune hemolytic anemia due to a non-complement-activating IgG 1k cold antibody with Pra specificity. Transfusion. 1990;30:838–843.
    1. Silberstein LE, Berkman EM, Schreiber AD. Cold hemagglutinin disease associated with IgG cold reactive antibody. Ann Intern Med. 1987;106:238–242.
    1. Feizi T, Kabat EA, Vicari G, Anderson B, Marsh WL. Immunochemical studies on blood groups: XLVII. The I antigen complex precursors in the A, B, H, Lea and Leb blood group system: hemagglutination inhibition studies. J Exp Med. 1971;133:39–52.
    1. Chapman J, Murphy MF, Waters AH. Chronic cold hemagglutinin disease due to an anti-M-like autoantibody. Vox Sang. 1982;42:272–277.
    1. von dem Borne AE, Mol JJ, Joustra-Maas N, Pegels JG, Langenjuijsen MMAC, Engelfriet CP. Autoimmune hemolytic anemia with monoclonal IgM (K) anti-P cold autohemolysins. Br J Haematol. 1982;50:345–350.
    1. Capra JD, Dowling P, Cook S, Kunkel HG. An incomplete cold-reactive λ-G antibody with i specificity in infectious mononucleosis. Vox Sang. 1969;16:10–17.
    1. Fellous M, Gerbal A, Tessier C, Frezal J, Dausset J, Salmon C. Studies on the biosynthetic pathway of human P erythrocyte antigens using somatic cells in culture. Vox Sang. 1974;26:518–536.
    1. Gehrie EA, Nian H, Young PP. Brown recluse spider bite mediated hemolysis: clinical features, a possible role for complement inhibitor therapy and reduced RBC surface glycophorin A as a potential biomarker of venom exposure. Plos One. 2013;8:e76558.
    1. McDade J, Aygun B, Ware RE. Brown recluse spider (Loxosceles reclusa) envenomation leading to acute hemolytic anemia in six adolescents. J Pediatr. 2010;156:155–157.
    1. Salama A, Janvier D, Mayer B, Saison C, Moscatelli H, Aucouturier F, Yilmaz P, Arnaud L, Wild V, Knop S, Cartron J-P. Lethal autoimmune hemagglutination due to an immunoglobulin A autoagglutinin with Band 3 specificity. Transfusion. 2014;54:1988–1995.
    1. Arndt P, Do JB, Garratty G, Kuriyan MA, Strair RK, Baranwal A. A high-titer, high-thermal amplitude autoanti-B associated with acrocyanosis but no obvious hemolytic anemia. Transfusion. 2003;43:1133–1137.
    1. Arndt P, Leger RM, Garratty G. Serologic findings in in autoimmune hemolytic anemia associated with immunoglobulin M warm autoantibodies. Transfusion. 2009;49:235–242.
    1. Sokol RJ, Booker DJ, Stamps R, Booth J R, Hook V. IgA red cell autoantibodies and autoimmune hemolysis. Transfusion. 1997;37:175–181.
    1. Silverstein MN, Gomes MR, Elveback LR, ReMine WH, Linman JD. Idiopathic acquired hemolytic anemia: survival in 117 cases. Arch Intern Med. 1972;129:85–87.
    1. Dausset J, Colombani J. The serology and the prognosis of 128 cases of autoimmune hemolytic anemia. Blood. 1959;14:1280–1301.
    1. Pullarkat V, Ngo M, Iqbal S, Espina B, Liebman HA. Detection of lupus anticoagulant identifies patients with autoimmune haemolytic anaemia at increased risk of venous thromboembolism. Br J Haematol. 2002;118:1166–1169.
    1. Hendrick AM. Auto-immune haemolytic anaemia - a high-risk disorder for thromboembolism? Hematology. 2003;8:53–56.
    1. Habibi B, Homberg JC, Schaison G, Salmon C. Autoimmune hemolytic anemia in children: a review of 80 cases. Am J Med. 1974;56:61–69.
    1. Buchanan GR, Boxer LA, Nathan DG. The acute and transient nature of idiopathic immune hemolytic anemia in childhood. J Pediatr. 1976;88:780–783.
    1. Heisel MA, Ortega JA. Factors influencing prognosis in childhood autoimmune hemolytic anemia. Am J Pediatr Hematol Oncol. 1983;5:147–152.
    1. Sokol RJ, Hewitt S, Stamps BK, Hitchen PA. Autoimmune haemolysis in childhood and adolescence. Acta Haematol. 1984;72:245–257.
    1. Wang WC. Evans syndrome in childhood: pathophysiology, clinical course, and treatment. Am J Pediatr Hematol Oncol. 1988;10:330–338.

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