Hemolytic anemia

Disease Description (Causes and Symptoms)

Hemolytic anemia is anemia caused by red blood cells (RBCs) being destroyed abnormally quickly before completing their normal lifespan (approximately 100–120 days). The bone marrow compensatorily increases red blood cell production, but anemia occurs when the rate of destruction exceeds production.

主要原因

• Intrinsic red blood cell abnormalities: G6PD deficiency, sickle cell disease, hereditary spherocytosis, etc.
• Immunologic causes: autoimmune hemolytic anemia (warm AIHA, cold agglutinin disease)—antibodies in the body target red blood cells.
• Extrinsic factors: medications (penicillin-induced type, methyldopa, quinine, etc.), infections (e.g., malaria), burns, mechanical damage (artificial heart valves), etc.
• Rare causes: complement-related disorders such as paroxysmal nocturnal hemoglobinuria (PNH).

Summary of Pathophysiology

• Hemolysis causes increased indirect (unconjugated) bilirubin and LDH, decreased blood haptoglobin, and increased reticulocytes (RET).
• Splenomegaly may occur when destruction takes place in the spleen (or liver), and chronic hemolysis can cause complications such as bilirubin gallstones or leg ulcers.

Main Symptoms

• Fatigue, dizziness, pallor, shortness of breath during exertion (tachycardia), jaundice (yellowing of the skin and sclera), dark urine (hemolysis breakdown products), splenomegaly, right upper quadrant pain related to gallstones, and skin ulcers in chronic cases.

Treatment Methods and Precautions

Treatment varies depending on the cause. The main approaches are as follows.

General and Supportive Treatment

• If anemia is severe, consider transfusion (red blood cell transfusion).
• Folic acid supplementation: folic acid requirements increase due to persistently elevated reticulocyte production.
• Discontinue the causative medication (in cases of drug-induced hemolysis) and treat infections.

Immune-Mediated Hemolytic Anemia

• First-line treatment (warm AIHA): high-dose corticosteroids (such as prednisone).
• If steroid-refractory or recurrent: consider antibody therapy such as rituximab and immunosuppressants (e.g., azathioprine and cyclosporine).
• In treatment-resistant cases, or when red blood cells are primarily destroyed in the spleen: splenectomy may be considered in selected patients.

Cold Agglutinin Disease (CAD)

• Avoid exposure to cold and consider newer treatments such as rituximab or complement inhibitors (e.g., sutimlimab).

Disease-Specific Treatments

• G6PD deficiency: avoid triggering drugs (certain antimalarials, sulfonamides, etc.) and substances that cause oxidative stress; provide supportive care during acute hemolysis.
• Sickle cell disease: maintain hydration and oxygenation, manage pain and infections, use hydroxyurea (to reduce symptoms and attacks), regular transfusions/exchange transfusions, and consider hematopoietic stem cell transplantation in severe cases.
• PNH: complement inhibitors (such as eculizumab and ravulizumab) reduce the risk of hemolysis and thrombosis.

Surgery and Vaccination

• After splenectomy, vaccination against pneumococcus, meningococcus, and Hib is recommended, along with education on infection prevention.

Precautions (Complications and Self-Care)

• Emergency treatment is necessary in cases of acute hemolysis or severe anemia (risk of tachycardia and heart failure).
• Chronic hemolysis increases the risk of gallstones, abnormal iron absorption (due to red blood cell destruction), chronic fatigue, leg ulcers, and high-output heart failure.
• The risk of infection increases after splenectomy—vaccination and prompt antibiotic therapy are necessary.
• In conditions such as PNH, the risk of thrombosis is high, so appropriate evaluation, prevention, and treatment are necessary.

Outpatient Visit Checkpoints (What to Prepare and Example Questions)

Items to Bring (Recommended)

• A list of all medications currently being taken, including prescription drugs, OTC medications, and supplements
• Recent test results (recent CBC, reticulocytes, bilirubin, LDH, haptoglobin, direct Coombs test, etc.)
• A history of recent hospitalizations, transfusions, and surgeries (especially whether a splenectomy was performed)
• Family history (whether there is hereditary anemia)
• A record of when symptoms began and how they have changed (jaundice, changes in urine color, fever, pain, etc.)

Items to Confirm Before Speaking with the Doctor (Examples)

• Recent colds, infections, medication use, and clinically new symptoms (chest pain, shortness of breath, decreased consciousness)
• If applicable, the possibility of pregnancy and whether contraception is being used (this may affect treatment choices)

Examples of General Questions to Ask the Doctor

• What is the exact cause of this anemia? What additional tests are needed?
• What treatment is recommended as first-line treatment in my case, and what side effects can be expected?
• If a transfusion is needed, when is it recommended, and what are the risks associated with transfusion?
• How likely is it that I will need a splenectomy or immunosuppressive treatment?

Examples of Disease-Specific Questions

• (If autoimmune disease is suspected) If the direct Coombs (DAT) test is positive, how does the treatment strategy differ depending on the antibody type?
• (If a hereditary condition or G6PD deficiency is suspected) Do you recommend genetic testing? If I have G6PD deficiency, which medications and foods must I avoid?
• (If PNH is suspected) What are the indications, advantages, and disadvantages of complement inhibitor treatment? How will the risk of thrombosis be managed?

Key Diagnostic Summary (Test Findings at a Glance)

• Blood tests: decreased Hb, increased reticulocytes (compensatory), increased LDH, increased indirect bilirubin, and decreased haptoglobin.
• Peripheral smear: observation of red blood cell morphologies (spherocytes, fragmented red blood cells, bite cells, sickle cells, etc.).
• Direct/indirect Coombs (DAT): essential for diagnosing immune hemolysis.
• Additional tests: hemoglobin electrophoresis (sickle cell disease/genetic abnormalities), G6PD enzyme testing, osmotic fragility testing (spherocytes), flow cytometry (CD55/59) for PNH, and abdominal ultrasonography (to check the spleen and gallstones).