Autoimmune hemolytic anemias
Autoimmune hemolytic anemia is antibody-mediated red cell destruction confirmed by a positive direct antiglobulin (Coombs) test, split into warm IgG disease with splenic clearance and spherocytes and cold agglutinin IgM disease with complement-mediated agglutination worse in the cold. Warm disease is treated with glucocorticoids first and cold agglutinin disease with cold avoidance and rituximab, and roughly half have an identifiable secondary cause that must be sought and treated.
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What this article covers
- Overview
Definition: autoimmune hemolytic anemia (AIHA) is premature red cell destruction driven by autoantibodies against erythrocyte surface antigens, confirmed by a positive direct antiglobulin (Coombs) test.
- Epidemiology
Warm AIHA is the dominant subtype; cold agglutinin disease is less common, and paroxysmal cold hemoglobinuria is the least common cause overall.
- Risk factors
Underlying lymphoproliferative disorder: CLL and B-cell non-Hodgkin lymphomas predispose to warm AIHA; the same disorders, plus Waldenstrom macroglobulinemia and MGUS, predispose to cold agglutinin disease (chronic lymphocytic leukemia).
- Pathophysiology
Warm AIHA, extravascular clearance: pathogenic IgG autoantibodies (may or may not fix complement) recognize Rh-type antigens on the erythrocyte surface; splenic macrophages bind the Fc portion of the…
- Clinical features
Anemia symptoms of variable severity: fatigue, dyspnea on exertion, and pallor, ranging from mild and compensated to severe and hemodynamically significant depending on hemolysis rate and marrow compensation.
- Differential diagnosis
Thrombotic thrombocytopenic purpura and other thrombotic microangiopathies: negative DAT, schistocytes rather than spherocytes or agglutination, severe thrombocytopenia; ADAMTS13 activity below 10%…
- Diagnosis
Establish AIHA with evidence of hemolysis plus a positive DAT, then subtype by the antiglobulin pattern: anti-IgG positive (with or without anti-C3) defines warm AIHA, positive in about 95% of cases…
- Management
Stabilize first if severe or symptomatic anemia: transfuse when hemoglobin is below 7 g/dL or the patient has hemodynamic instability or significant cardiopulmonary comorbidity, regardless of…
- Complications
Life-threatening anemia and cardiovascular decompensation: rapid or severe hemolysis can outpace marrow compensation, precipitating high-output heart failure or ischemia in patients with cardiopulmonary disease.
- Prognosis
Response-driven outlook in warm AIHA: about two-thirds respond to glucocorticoids alone, and most of the remainder respond to rituximab or splenectomy, so durable remission is achievable in most…
- Prevention
No primary prevention exists for idiopathic AIHA; prevention targets recognizing and removing secondary triggers and preventing complications of chronic hemolysis and its treatment.
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Related articles
- Hemolytic anemia: an overview
Hemolytic anemia is premature red cell destruction confirmed by a high reticulocyte count and LDH with low haptoglobin and high indirect bilirubin. The approach then classifies disease by smear findings and a direct antiglobulin test, separating immune from non-immune and inherited from acquired causes to direct treatment.
- Hereditary spherocytosis
Hereditary spherocytosis is an inherited red cell membrane defect, usually autosomal dominant, that produces rigid spherocytes trapped and destroyed in the spleen. It presents with anemia, jaundice, splenomegaly, and pigment gallstones, is diagnosed by spherocytes with elevated MCHC and a negative direct antiglobulin test, and is confirmed by eosin-5-maleimide binding or osmotic fragility testing, with folic acid and splenectomy as the mainstays of treatment.
- Chronic lymphocytic leukemia
Chronic lymphocytic leukemia is the most common adult leukemia, a clonal proliferation of mature B lymphocytes usually discovered as incidental lymphocytosis in older adults with smudge cells on smear. Diagnosis rests on absolute B-lymphocytosis with a characteristic flow cytometry immunophenotype, and asymptomatic early-stage disease is observed while symptomatic or progressive disease is treated with targeted agents such as ibrutinib and venetoclax.
- Thrombotic thrombocytopenic purpura (TTP)
Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy caused by severe ADAMTS13 deficiency that lets ultralarge von Willebrand factor multimers drive platelet microthrombi; the key dyad of microangiopathic hemolytic anemia plus thrombocytopenia without another cause mandates the PLASMIC score, an ADAMTS13 activity and inhibitor level, and emergent plasma exchange started before results return.