Autoimmune Haemolytic anaemia (AIHA) ✅
Related Subjects:
| Alpha Thalassaemia
| Anaemia of Chronic Disease
| Aplastic Anaemia
| Autoimmune Haemolytic Anaemia (AIHA)
Autoimmune Haemolytic Anaemia (AIHA) is an acquired group of disorders in which increased red blood cell (RBC) destruction (haemolysis) is caused by autoantibodies directed against the patient's own RBC surface antigens. These autoantibodies are typically of the IgG or IgM class. It is a rare but potentially life-threatening condition requiring urgent haematological assessment.
ℹ️ About & Pathophysiology
- Autoantibodies bind to RBCs, leading to premature destruction and shortened red cell survival.
- Extravascular haemolysis: Antibody-coated RBCs are phagocytosed by macrophages, primarily in the spleen (common in IgG/Warm AIHA) or liver. Partial phagocytosis leads to the formation of spherocytes.
- Intravascular haemolysis: Antibodies strongly fix complement, leading to direct RBC lysis within the blood vessels (common in IgM/Cold AIHA).
- High RBC turnover increases the demand for folate, often necessitating lifelong or prolonged supplementation.
🌡️ Classification by Temperature
- Warm AIHA (wAIHA):
- Antibodies react optimally at body temperature (37°C).
- Accounts for 70–80% of cases.
- Typically mediated by IgG antibodies (often targeting Rhesus antigens).
- Mainly causes extravascular haemolysis in the spleen.
- Cold Agglutinin Disease / Cold AIHA:
- Antibodies react optimally at low temperatures (usually 4°C but can react up to 30°C in peripheral extremities).
- Typically mediated by IgM antibodies which strongly fix complement.
- Mainly causes intravascular haemolysis and hepatic clearance.
- Patients may experience acrocyanosis (bluish, painful discoloration of fingers, toes, nose, ears) and livedo reticularis on cold exposure.
- Paroxysmal Cold Haemoglobinuria (PCH):
- A rare subtype, most common in children following viral infections.
- Caused by the Donath-Landsteiner antibody (a biphasic IgG antibody that binds in the cold and lyses RBCs via complement when warmed).
📌 Causes & Associations
- Idiopathic (approx. 50%): No identifiable underlying cause.
- Secondary (approx. 50%):
- Malignancies: Lymphoproliferative disorders (Chronic Lymphocytic Leukaemia [CLL], Non-Hodgkin Lymphoma).
- Autoimmune Diseases: Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis, Evans Syndrome (AIHA + Immune Thrombocytopenia).
- Infections:
- Mycoplasma pneumoniae and Epstein-Barr Virus (EBV) → classically cause Cold AIHA.
- Cytomegalovirus (CMV), HIV.
- Medications: Penicillins, cephalosporins, methyldopa, fludarabine, mefenamic acid.
🩺 Clinical Features
- Symptoms of anaemia: Fatigue, dyspnoea, palpitations, pallor.
- Signs of haemolysis: Jaundice (unconjugated hyperbilirubinaemia), gallstones (pigment stones in chronic cases), and dark urine (haemoglobinuria/urobilinogen).
- Organomegaly: Splenomegaly is common, particularly in Warm AIHA.
- Cold-specific symptoms: Raynaud's phenomenon, acrocyanosis, and livedo reticularis in Cold AIHA.
🔎 Investigations
- Full Blood Count (FBC): Normocytic or macrocytic anaemia (macrocytosis due to high reticulocyte count).
- Haemolysis Screen:
- ↑ Reticulocytes (bone marrow compensating).
- ↑ Lactate dehydrogenase (LDH).
- ↑ Unconjugated bilirubin.
- ↓ Haptoglobin (binds free haemoglobin).
- Direct Antiglobulin Test (DAT / Coombs Test): The definitive diagnostic test.
- Warm AIHA: DAT strongly positive for IgG (with or without C3d).
- Cold AIHA: DAT positive for complement C3d only (IgM washes off during testing).
- Blood Film: Prominent spherocytes, polychromasia (reticulocytes), and potentially RBC agglutination (clumping) in cold AIHA.
- Cross-matching: Often difficult due to pan-reactivity of the autoantibody.
💊 Management
- General Supportive Care:
- Folic acid supplementation: Essential (usually 5 mg daily) to prevent megaloblastic crisis due to high bone marrow turnover.
- Blood Transfusion: Should not be withheld in life-threatening anaemia despite cross-matching difficulties. The lab will provide the "least incompatible" blood. Transfuse slowly and monitor closely.
- VTE Prophylaxis: Active haemolysis carries a high risk of venous thromboembolism; prophylactic heparin should be considered in hospitalised patients.
- Warm AIHA Management:
- First-line: Corticosteroids (e.g., Prednisolone 1 mg/kg).
- Second-line: Rituximab (anti-CD20 monoclonal antibody) is now often preferred over splenectomy.
- Third-line: Splenectomy or immunosuppressive agents (azathioprine, mycophenolate, cyclophosphamide).
- Cold AIHA (Cold Agglutinin Disease) Management:
- Crucial difference: Corticosteroids and splenectomy are generally ineffective and should be avoided.
- First-line: Strict avoidance of cold (thermal protection, heated gloves). Treat underlying infections.
- Targeted therapy: Rituximab (with or without bendamustine).
- Newer agents: Complement pathway inhibitors (e.g., Sutimlimab) for severe, refractory cases.
- Severe crises: Plasma exchange can temporarily remove circulating IgM. Transfused blood must be administered through a blood warmer.
🧑⚕️ Case Examples - Autoimmune Haemolytic Anaemia (AIHA)
-
Case 1 (Warm AIHA - Primary): 🌡️
A 45-year-old woman presents with progressive fatigue, jaundice, and dark urine. Examination reveals mild splenomegaly. Bloods: Hb 7.8 g/dL, reticulocytosis, raised LDH, indirect hyperbilirubinaemia. Direct antiglobulin (Coombs) test positive for IgG.
Diagnosis: Warm autoimmune haemolytic anaemia (IgG-mediated).
Management: High-dose corticosteroids (prednisolone), folic acid supplementation, and consideration of rituximab if refractory. Thromboprophylaxis while haemolysing.
-
Case 2 (Cold AIHA - Infection-Related): ❄️
A 28-year-old man develops fatigue, acrocyanosis, and haemoglobinuria after a recent Mycoplasma pneumoniae infection. On cold exposure, his fingers turn blue and painful. Bloods: Hb 9.0 g/dL, raised LDH, Coombs test positive for C3d only. Blood film shows red cell agglutination.
Diagnosis: Cold agglutinin disease (IgM-mediated, post-infective).
Management: Strict avoidance of cold exposure, supportive care, and treat underlying infection. Condition is usually self-limiting, but rituximab can be considered in persistent/severe disease. Steroids are avoided.
-
Case 3 (Secondary Warm AIHA - SLE / Evans Syndrome): 🧬
A 32-year-old woman with known systemic lupus erythematosus (SLE) presents with pallor, jaundice, and petechiae. Bloods show Hb 7.2 g/dL, platelets 22 × 10&sup9;/L, reticulocytosis, raised LDH, and positive Coombs test for IgG. Peripheral smear reveals spherocytes.
Diagnosis: Evans Syndrome (Warm AIHA + Immune Thrombocytopenia secondary to SLE).
Management: Corticosteroids with optimisation of SLE control (hydroxychloroquine, immunosuppressants). Transfusion of "least incompatible" blood if haemodynamically unstable.
📋 References & UK Guidelines
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