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Chapter 24: Hemolytic Anemia Resulting from Warm-Reacting Antibodies

INTRODUCTION

  • In autoimmune hemolytic anemia (AHA), shortened red blood cell (RBC) survival is the result of host antibodies that react with autologous RBC.

  • AHA may be classified by whether an underlying disease is present (secondary) or not (primary or idiopathic) (Table 24–1).

  • AHA may also be classified by the nature of the antibody (Table 24–2).

  • "Warm-reacting" antibodies are usually of the IgG type, have optimal activity at 37°C, and bind complement.

  • "Cold-reacting" antibodies show affinity at lower temperatures (see Chap. 25).

  • Occasionally, mixed disorders occur with both warm and cold antibodies.

  • Warm antibody AHA is the most common type.

TABLE 24–1CLASSIFICATION OF WARM-ANTIBODY–MEDIATED AUTOIMMUNE HEMOLYTIC ANEMIA (AHA)
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TABLE 24–1 CLASSIFICATION OF WARM-ANTIBODY–MEDIATED AUTOIMMUNE HEMOLYTIC ANEMIA (AHA)

  1. On basis of presence or absence of underlying or significantly associated disorder

    1. Primary or idiopathic AHA (no apparent underlying disease)

    2. Secondary AHA

      1. Associated with lymphoproliferative disorders (e.g., Hodgkin or non-Hodgkin lymphoma)

      2. Associated with the rheumatic disorders, particularly systemic lupus erythematosus

      3. Associated with certain infections (e.g., Mycoplasma pneumoniae)

      4. Associated with certain non-lymphoid neoplasms (e.g., ovarian tumors)

      5. Associated with certain chronic inflammatory diseases (e.g., ulcerative colitis)

      6. Associated with ingestion of certain drugs (e.g., α-methyldopa)
TABLE 24–2MAJOR REACTION PATTERNS OF THE DIRECT ANTIGLOBULIN TEST AND ASSOCIATED TYPES OF IMMUNE INJURY
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TABLE 24–2 MAJOR REACTION PATTERNS OF THE DIRECT ANTIGLOBULIN TEST AND ASSOCIATED TYPES OF IMMUNE INJURY
Reaction Pattern Type of Immune Injury
IgG alone

Warm-antibody autoimmune hemolytic anemia

Drug-immune hemolytic anemia: hapten drug adsorption type or autoantibody type
Complement alone

Warm-antibody autoimmune hemolytic anemia with subthreshold IgG deposition

Cold-agglutinin disease

Paroxysmal cold hemoglobinuria

Drug-immune hemolytic anemia: ternary complex type
IgG plus complement

Warm-antibody autoimmune hemolytic anemia

Drug-immune hemolytic anemia: autoantibody type (rare)

Source: Williams Hematology, 8th ed, Chap. 53, Table 53–4, p. 787.

ETIOLOGY AND PATHOGENESIS

  • AHA occurs in all age groups, but the incidence rises with age, probably because the frequency of lymphoproliferative malignancies increases with age.

  • In primary AHA, the autoantibody often is specific for a single RBC membrane protein, suggesting that an aberrant immune response has occurred to an autoantigen or a similar immunogen; a generalized defect in immune regulation is not seen.

  • In secondary AHA, the autoantibody most likely develops from an immunoregulatory defect.

  • Certain drugs (e.g., α-methyldopa) can induce specific antibodies in otherwise normal individuals by some unknown mechanism. These subside spontaneously when the drug is stopped.

  • The red cells of some apparently normal individuals may be found coated with warm-reacting autoantibodies similar to those of patients with AHA. Such antibodies are noted in otherwise normal blood donors at a frequency of 1 in 10,000. A few develop AHA.

  • RBC autoantibodies in AHA are pathogenic.

  • RBCs that lack the targeted antigen have a normal survival.

  • Transplacental passage of autoantibodies to a fetus can cause ...

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