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Autoimmune hemolytic anemia

Last updated: October 18, 2021

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Autoimmune hemolytic anemias (AIHAs) are a collection of disorders characterized by the destruction of RBCs through antibody-mediated hemolysis (extravascular and/or intravascular). There are two broad types, categorized by the temperature at which the antigen-antibody reactions maximally occur: cold agglutinin hemolytic anemia (cold AIHA) and warm agglutinin hemolytic anemia (warm AIHA). AIHAs can be either idiopathic or secondary to another disease e.g., infectious, lymphoproliferative, or autoimmune diseases. Cold AIHA and warm AIHA share some characteristics, e.g., they can both present with clinical signs of anemia and laboratory signs of hemolysis, and produce symptomatic anemia severe enough to require blood transfusion. However, their pathophysiology, etiology, epidemiology, clinical and diagnostic features, and targeted treatments all have key differences. Careful clinical and diagnostic evaluation (including direct Coombs testing, antibody titers, and peripheral blood smear) can help distinguish between the types, however, occasionally patients may have a mixed-type AIHA or unusual clinical presentations and laboratory findings. Management depends on the clinical presentation, etiology, and subtype, and is typically performed in consultation with a hematologist. Treatments include stabilization with blood transfusion and temporizing measures (e.g., plasmapheresis, plasma exchange), systemic immunomodulators (e.g., glucocorticoids, rituximab), treatment of underlying conditions, supportive care, and in warm AIHA, splenectomy.

Typical distinguishing features of autoimmune hemolytic anemias [1][2]
Cold AIHA Warm AIHA
Pathophysiology
Etiology
Clinical features

Diagnostics

Acute therapy
Long-term management

Typical biochemical findings in hemolysis include haptoglobin, LDH concentration, indirect bilirubin concentration, peripheral blood smear abnormalities (e.g., reticulocytes, schistocytes, spherocytes, polychromasia), and urinalysis abnormalities (e.g., hemoglobinuria, hemosiderinuria, and urobilinogen).

Background [3][4][5]

Pathophysiology [4]

Etiology [4]

Cold weather is MMMMiserable: Cold (IgM) AIHA is seen in Malignancy (CLL), Mycoplasma pneumonia, and Mononucleosis.

Clinical features

Diagnostics [4][6][9]

Spherocytes may be seen in both cold AIHA and warm AIHA. However, abundant spherocytosis is characteristic of warm AIHA.

Management [5][9][10]

Approach

The goal is to reduce cold-induced symptoms, control hemolysis, and improve anemia. Hematology consult is advised.

  • Compensated hemolysis and mild or absent circulatory symptoms : close surveillance
  • Significant clinical manifestations: Start acute therapy.
  • CAD: Consider chronic therapy (systemic immunomodulatory).
  • CAS: Treat the underlying condition
  • Advise all patients to avoid exposure to the cold.
  • Consider folic acid supplementation in all patients.
  • Manage disease complications: Venous thromboembolism (VTE) [11]

Spontaneous remission is rare in CAD but is common in CAS secondary to infection (e.g., Mycoplasma) and typically occurs within a few weeks of onset. [4][6]

Acute therapy

Long-term therapy

Splenectomy is not recommended for cold AIHA. It is not effective as most extravascular hemolysis occurs in the liver.

Background [5][7][12][13]

Pathophysiology [15]

Warm weather is Great”: Warm AIHA is IgG mediated.

Etiology

Clinical features

Diagnostics [10]

Consider warm AIHA in patients with severe anemia for whom the blood bank is unable to find crossmatch-compatible blood units.

Management [5][10][14]

Approach

The goal is to control hemolysis and improve anemia. Early specialist consultation is advised (e.g., hematology, intensive care).

  • Manage severe disease acutely.
  • Address potential secondary causes (see “Etiology”). [17]
    • Hold any potentially causative medications.
    • Identify and manage underlying conditions.
  • Consider the need for chronic systemic immunomodulators.
  • Observation without immunosuppressive interventions may be appropriate for patients with mild asymptomatic anemia.
  • Manage disease complications: e.g., VTE
  • Monitor for relapses and consider repeated therapeutic intervention.

Acute therapy

Do not delay a potentially life-saving blood transfusion in unstable patients with severe anemia, even if crossmatched blood is unavailable. Use type-specific uncrossmatched blood in close consultation with the blood bank. [14]

Long-term therapy

References: [5][7][12][13]

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