Autoimmune hemolytic disease

• Disease name: Autoimmune hemolytic disease (Autoimmune hemolytic disease, AIHA)

1) Disease description (causes and pathophysiology, main symptoms)

• Definition/pathophysiology: An acquired hemolytic anemia in which autoantibodies (such as IgG or IgM) bind to antigens on the surface of red blood cells, causing destruction through complement activation or phagocytosis. It is classified according to the temperature at which the antibodies act as warm type (warm, mainly IgG), cold type (cold agglutinin disease, mainly IgM), and Donath–Landsteiner type (Paroxysmal cold hemoglobinuria, PCH; D–L antibodies).
• Causes:
  • Primary (unknown cause) or secondary (lymphoma, systemic lupus erythematosus (SLE), infections (Mycoplasma pneumoniae, viruses, etc.), certain drugs, lymphoid neoplasms, etc.).
  • The cold type may worsen after infections or in association with B-cell proliferative disorders, while PCH may occur after infections in children or be associated with syphilis or viruses.
• Main symptoms:
  • Fatigue and lack of energy, pallor, jaundice (of the skin and whites of the eyes), dark (reddish-brown) urine, tachycardia, fever, abdominal pain, splenomegaly and hepatomegaly, etc.
  • The cold type worsens with exposure to cold (pallor or bluish discoloration of the extremities, with possible hematuria).

2) Treatment methods (standard treatments, medications, procedures/surgery, lifestyle management and precautions)

• Diagnostic indicators (important for treatment decisions): CBC (low hemoglobin), increased reticulocytes, increased indirect bilirubin and LDH, hemoglobin in plasma and urine, decreased haptoglobin, positive direct antiglobulin test (DAT, Coombs test), cold agglutinin and Donath–Landsteiner tests, etc.
• Warm type (AIHA, IgG-driven)
  • First-line: Oral steroids (e.g., prednisone) — symptoms usually improve within 5–10 days; maintenance therapy may be necessary.
  • Second-line (when steroids are ineffective or cause adverse effects): Rituximab (anti-CD20), immunosuppressants (azathioprine, mycophenolate, etc.), splenectomy (in some patients), and high-dose intravenous immunoglobulin (IVIG, in acute severe cases).
  • Transfusion: If necessary, use red blood cells with minimized cross-reactivity and, where possible, warmed blood (warmed RBC). Appropriate consultation with the blood bank is necessary before transfusion.
• Cold type (Cold agglutinin disease, CAD; IgM- and complement-mediated)
  • Basic management: Avoid exposure to cold (keep warm) and treat the underlying disease (infection, lymphoma, etc.).
  • Medications: Rituximab alone or in combination therapy (effective); recently, a complement C1s inhibitor (e.g., sutimlimab, proven effective in CAD) may also be used.
  • Plasma exchange (plasmapheresis): Effective for a short period in acute, severe hemolysis (especially when large amounts of IgM are present).
  • Splenectomy has limited effectiveness (destruction occurs mainly in the liver in many cases).
• PCH (Donath–Landsteiner)
  • Usually transient and resolves spontaneously (common after infections in children). In severe cases, transfusion and supportive treatment are used; immunosuppressive treatment is rarely used.
• Treatment precautions related to complications and monitoring:
  • Regular monitoring is necessary for steroid adverse effects (hypertension, hyperglycemia, risk of infection, osteoporosis, weight gain, etc.).
  • Patients with chronic hemolysis should be aware of the increased risks of gallstones, iron overload or deficiency, and thrombosis.
  • Vaccination before surgery (splenectomy) is recommended, especially against pneumococcus, meningococcus, and H. influenzae.
  • Consider anticoagulation: After severe anemia has improved or in high-risk groups, thrombosis prevention should be discussed.

3) Outpatient visit checklist (items to bring, information to provide during the visit, and example questions)

• Items to bring and test records:
  • List of medications currently being taken (including steroids, immunosuppressants, and anticoagulants)
  • Recent test results (recent CBC, total bilirubin and liver enzyme levels, LDH, haptoglobin, DAT results, etc.) or test reports
  • Transfusion history (whether there has been a recent transfusion and any reactions)
  • Recent infection history (respiratory infection, gastrointestinal symptoms, etc.) and when it began
  • Symptom diary: changes in fatigue, shortness of breath, urine color, fever, spleen-related symptoms, abdominal pain, etc., and when they occurred
  • Warmth measures and history of exposure to cold (if the cold type is suspected)
• Examples of questions to prepare for the outpatient visit (items for the patient to consider):
  • When did the symptoms begin? What factors make them worse or better?
  • Have you recently had an infection or started taking a new medication?
  • Have you ever received a blood transfusion? Did you have any problems after the transfusion?

4) Examples of general questions to ask the doctor

• "What do you think is the cause of this condition? Are there any additional tests I need?"
• "What is the recommended treatment sequence? What is the goal of first-line treatment?"
• "What are the main adverse effects of this medication (e.g., steroids or rituximab), and what symptoms should be monitored?"
• "If a transfusion is needed, what preparation and precautions are required?"
• "What is the long-term prognosis, and how likely is recurrence?"

5) Examples of disease-specific questions (1–2)

• If the warm type is suspected: "If the DAT (direct antiglobulin test) is IgG-positive, how long should treatment with steroids continue? What criteria are used to assess the treatment response?"
• If the cold type is suspected: "Besides lifestyle measures to avoid the cold, in what situations are treatment with a complement inhibitor (e.g., sutimlimab) or rituximab needed? What are the expected effects and adverse effects of treatment?"

Additional reference (brief): Diagnosis and treatment vary according to each patient's medical history, test results, severity, and underlying diseases. In patients with severe anemia, acute hemolysis, or unstable condition, emergency treatment, hospitalization, and consultation with the blood bank and hematology department are necessary.