Acquired Autoimmune Hemolytic Anaemia

Mr. Topesh Patle

Introduction

  • Acquired Autoimmune Hemolytic Anaemia (AIHA) is a rare blood disorder in which the immune system produces autoantibodies that attack and destroy red blood cells (RBCs), leading to premature hemolysis.

  • It is acquired, meaning it develops later in life rather than being inherited.

  • The destruction of RBCs results in anaemia and related symptoms.

Types of AIHA

There are three main types, based on the temperature at which the antibodies work best:

A. Warm AIHA

  • Most common (about 70–80% of cases).

  • Antibodies: IgG (sometimes IgA).

  • Best active at body temperature (37°C).

  • RBCs mainly destroyed in the spleen (extravascular hemolysis).

  • Associated with:

    • Autoimmune diseases (e.g., SLE, rheumatoid arthritis).

    • Blood cancers (CLL, lymphoma).

    • Medicines (methyldopa, penicillin).

  • Peripheral smear: spherocytes.

B. Cold AIHA (Cold Agglutinin Disease)

  • Antibodies: IgM.

  • Work best in cooler temperatures (<30°C).

  • Cause clumping (agglutination) of RBCs and complement activation.

  • RBCs destroyed in liver and circulation (intravascular and extravascular hemolysis).

  • Associated with:

    • Infections (Mycoplasma pneumoniae, EBV, HIV).

    • Lymphoid cancers.

  • Clinical feature: acrocyanosis (blue fingers/toes in cold).

C. Paroxysmal Cold Hemoglobinuria (PCH)

  • Very rare, usually in children after viral illness.

  • Antibody: Donath–Landsteiner (IgG).

  • Attacks RBCs when body rewarms after cold exposure.

  • Often self-limiting.

 

Causes of AIHA

  • Primary (Idiopathic): No clear underlying reason (about 50% of cases).

  • Secondary (due to other conditions):

    • Autoimmune diseases: SLE, rheumatoid arthritis.

    • Blood cancers: CLL, lymphoma.

    • Infections: EBV, HIV, Mycoplasma.

    • Drugs: penicillin, cephalosporins, methyldopa.

 

Symptoms

  • From anemia: fatigue, weakness, pale skin, dizziness, rapid heartbeat, shortness of breath.

  • From hemolysis: yellow eyes (jaundice), dark urine (hemoglobinuria), enlarged spleen, gallstones.

  • Warm AIHA: gradual tiredness, enlarged spleen.

  • Cold AIHA: cold hands/feet, bluish skin, Raynaud’s phenomenon, hemoglobin in urine after cold exposure.

  • Severe cases: chest pain, fainting, heart strain.

Diagnosis

Blood tests to confirm AIHA:

  1. Complete Blood Count (CBC):

    • Low hemoglobin.

    • Often normal-sized (normocytic) RBCs.

  2. Reticulocyte count: High (bone marrow trying to make more RBCs).

  3. Peripheral smear:

    • Warm AIHA: spherocytes (small round RBCs).

    • Cold AIHA: RBC clumping (agglutination).

  4. Biochemistry:

    • High indirect bilirubin (from RBC breakdown).

    • High LDH.

    • Low haptoglobin.

  5. Direct Antiglobulin Test (DAT/Coombs test):

    • Positive in most patients.

    • IgG positive → Warm AIHA.

    • C3 positive → Cold AIHA.

    • Negative in rare cases (DAT-negative AIHA).

  6. Special tests:

    • Cold agglutinin titer.

    • Donath–Landsteiner test (for PCH).

    • Tests for underlying disease (ANA, viral serology, blood cancer markers).

 

Treatment

Warm AIHA

  • First-line:

    • Steroids (Prednisone 1 mg/kg/day).

    • Works in most patients; later slowly reduced.

  • Second-line (if steroids fail):

    • Rituximab (anti-CD20 antibody).

    • Splenectomy (removing spleen).

  • Other options:

    • Immunosuppressants (azathioprine, cyclophosphamide, cyclosporine).

  • Blood transfusion: May be needed in severe anemia, but matching is difficult because of antibodies.

Cold AIHA

  • Avoid cold exposure (keep warm).

  • Rituximab is effective in many cases.

  • New drug: Sutimlimab (blocks complement system, approved for Cold AIHA).

  • Steroids usually not useful.

  • Plasmapheresis (blood filtering) in severe cases.

Paroxysmal Cold Hemoglobinuria (PCH)

  • Avoid cold exposure.

  • Supportive care, blood transfusion if needed.

  • Usually gets better by itself.

 

Complications

  • Severe anemia → heart failure, breathlessness.

  • Gallstones from bilirubin buildup.

  • Blood clots (rare but possible).

  • Infections after splenectomy.

 

Prognosis

  • Warm AIHA: Most patients respond to steroids but some relapse.

  • Cold AIHA: Often long-term, needs ongoing management.

  • PCH: Usually temporary in children.