Autoimmune hemolytic anemia (AHA) is characterized
by shortened red blood cell (RBC) survival and the presence of autoantibodies directed
against autologous RBCs. A positive direct antiglobulin test (DAT,
also known as the Coombs test) is essential for diagnosis. Most
patients with AHA (80%) exhibit warm-reactive antibodies
of the immunoglobulin (Ig) G isotype on their red cells. Most of
the remainder of patients exhibit cold-reactive autoantibodies.
Two types of cold-reactive autoantibodies to RBCs are recognized:
cold agglutinins and cold hemolysins. Cold agglutinins are generally
of IgM isotype, whereas cold hemolysins usually are of IgG isotype.
The DAT may detect IgG, proteolytic fragments of complement (mainly
C3), or both on the RBCs of patients with warm-antibody AHA. In
cold-antibody AHA, only complement is detected because the antibody
dissociates from the RBCs during washing of the cells. About half
of patients with AHA have no underlying associated disease; these cases
are termed primary or idiopathic. Secondary cases are associated
with underlying autoimmune, malignant, or infectious diseases or
with ingestion of certain drugs.
Although most patients do not require transfusion
of RBCs, transfusion should not be withheld from those with symptomatic
anemia. In warm-antibody AHA, glucocorticoids are effective in slowing
the rate of hemolysis. Splenectomy is indicated for patients who require
an unacceptably high maintenance dose or prolonged administration
of glucocorticoids. Intravenous immunoglobulin may provide short-term
control of hemolysis. Immunosuppressive drugs and danazol have been
used successfully in refractory cases. In cold agglutinin- and cold
hemolysin-mediated hemolysis, keeping the patient warm and treating
underlying lymphoproliferative disorders usually are effective.
Rituximab has been effective in reported cases of both warm and
cold AHA. Drug-immune hemolytic anemia usually is ameliorated by
discontinuation of the offending drug.
Acronyms and Abbreviations
Acronyms and abbreviations
that appear in this chapter include: AHA, autoimmune hemolytic anemia; CLL,
chronic lymphocytic leukemia; DAF, decay accelerating factor; DAT,
direct antiglobulin test; HLA, human leukocyte antigen; HRF, homologous
restriction factor; HS, hereditary spherocytosis; IAT, indirect
antiglobulin test; Ig, immunoglobulin; IGHV, immunoglobulin heavy
chain variable region; PNH, paroxysmal nocturnal hemoglobinuria;
RBC, red blood cell; SLE, systemic lupus erythematosus.
The two main features of immune red blood cell (RBC) injury are (1)
shortened RBC survival in vivo and (2) evidence
of host antibodies reactive with autologous RBCs, most frequently
demonstrated by a positive direct antiglobulin test (DAT), also
known as the Coombs test. Most cases in adults are mediated by warm-reactive
autoantibodies. A smaller proportion of patients exhibit cold-reactive
autoantibodies or drug-related antibodies.
By the early 20th century, reticulocytes, spherocytes, and osmotic
fragility of RBCs had been described. Clinicians could diagnose
hemolytic anemia, but the distinction between congenital and acquired
forms was imprecise. Some clinicians even doubted the existence
of acquired hemolytic anemia.1 The sera of some
patients with hemolytic anemia directly agglutinated saline suspensions
of normal or autologous human RBCs. These serum factors, later shown
to be specific antibodies (largely of the immunoglobulin ...