Thalassemia

Disease Description (Causes and Symptoms)

• Definition: Thalassemia is a hereditary anemia caused by genetic defects in the globin chains (alpha or beta), resulting in reduced and abnormal hemoglobin synthesis. Consequently, ineffective erythropoiesis and hemolysis occur, leading to bone marrow expansion, skeletal deformities, and enlargement of the spleen and liver.
• Causes and pathophysiology: Autosomal inheritance (usually recessive) involving deletions or mutations of globin genes (there are 4 copies of the alpha genes and 2 copies of the beta genes). Depending on the extent of the defect, the condition ranges from asymptomatic carrier status → mild (minor) → severe (major) → fatal in the fetal period (deletion of all 4 alpha genes).
  • Beta type: Symptoms usually develop from 4–6 months after birth (because fetal hemoglobin decreases)
  • Alpha type: The range of symptoms is broad depending on the number of deleted genes
• Main symptoms:
  • Anemia-related: Pallor, fatigue, shortness of breath, breathlessness during exercise
  • Hemolysis-related: Jaundice, hyperbilirubinemia
  • Bone marrow and skeletal changes: Craniofacial skeletal deformities (changes in facial appearance)
  • Organ enlargement: Splenomegaly and hepatomegaly (abdominal distension)
  • Delayed growth and delayed sexual development
  • Many carriers are asymptomatic
• Key complication: Iron overload in the body (iron accumulation) due to repeated transfusions and ineffective erythropoiesis → damage to the heart, liver, and endocrine organs

Treatment Methods and Precautions

• Overview (treatment goals): Relieve anemia symptoms, maintain growth and development, prevent and manage organ damage (especially iron overload), and, when possible, provide definitive treatment (curative treatment).
• Medications, procedures, and surgery
  • Regular transfusions: For patients with severe (transfusion-dependent) disease, regular red blood cell transfusions (generally whole blood or packed red blood cells) are given to sustain life and support normal growth. The target pre-transfusion Hb level varies according to clinical guidelines, but is generally maintained around 9–10 g/dL.
  • Iron chelators: Essential for removing iron accumulated from repeated transfusions
    • Injectable: deferoxamine (subcutaneous or intravenous infusion)
    • Oral medications: deferasirox, deferiprone (each medication has its own indications and adverse-effect profile)
  • Splenectomy (partial or total): Considered in cases of excessive blood cell destruction, excessive transfusion requirements, or severe splenomegaly. May increase the risk of infection and thrombosis.
  • Hematopoietic stem cell transplantation (bone marrow transplantation): The only definitive (curative) treatment when a suitable donor (such as one with identical histocompatibility) is available. The success rate and indications are determined based on age, organ complications, and donor availability.
  • Gene therapy: In recent years, gene therapy (such as lentivirus-based gene delivery) has been applied under limited clinical approval or in research settings, suggesting the possibility of fundamental improvement for some patients (indications and availability vary by region and circumstances).
  • Supportive treatment: Folic acid supplementation (to support red blood cell production in the bone marrow), infection prevention (especially in patients who have undergone splenectomy)
• Diagnosis and monitoring (during treatment)
  • Regular blood tests (CBC, reticulocyte count), serum ferritin, liver function, cardiac function (echocardiography and cardiac MRI T2*), liver and cardiac iron assessment (MRI), endocrine function (growth hormone, thyroid, and glucose metabolism), etc.
  • Blood type and antibody testing (before transfusion)
• Lifestyle management and precautions
  • Use iron supplements only when clear iron deficiency is present (unnecessary iron administration can worsen iron overload)
  • Vaccination: For patients who have undergone splenectomy or are suspected of having functional asplenia, vaccination against Streptococcus pneumoniae, Neisseria meningitidis, and H. influenzae is recommended
  • Manage infection- and transfusion-related risks (transfusion-transmitted infections, alloimmunization)
  • Pregnancy and childbirth management: Multidisciplinary care is required during pregnancy (transfusion management, iron management, and fetal genetic counseling)
• Complications (major risks)
  • Cardiomyopathy (heart failure) due to iron overload, cirrhosis and liver dysfunction, endocrine disorders (growth delay, diabetes, thyroid and adrenal dysfunction), bone disease, and increased risk of infection after splenectomy, etc.
• Prognosis
  • Survival rates and quality of life are greatly improved with supportive treatment (regular transfusions + appropriate iron chelation).
  • Without appropriate treatment, severe forms may be fatal during childhood or adolescence.
  • Bone marrow transplantation or successful gene therapy may offer the possibility of a cure.

Checklist Before an Outpatient Visit (Including Items to Bring, Test Records, and Example Questions)

• Items to bring (recommended)
  • A list of all medications and supplements currently being taken (or recently discontinued), especially chelators, antibiotics, and anticoagulants
  • Recent transfusion records (date and frequency of recent transfusions), and Hb levels before and after transfusions
  • Recent test results: CBC, ferritin, liver function tests (LFTs), blood type and antibody testing, cardiac and liver MRI (T2*), and previous genetic testing (if available)
  • History of surgery, hospitalization, or splenectomy, and allergy records (especially transfusion-related allergies)
  • Family history (especially whether parents or siblings have anemia or carry thalassemia)
• Symptom and lifestyle records
  • Record the timing, frequency, and aggravating factors of symptoms such as fatigue, shortness of breath, jaundice, and abdominal distension (splenomegaly or hepatomegaly)
  • Growth delay (growth curve in children), menstruation (women), and whether pregnancy is planned
• Tests that may be performed during an outpatient visit (if necessary)
  • CBC, reticulocyte count, ferritin, bilirubin, LDH, liver function, and thyroid/endocrine tests
  • Blood type and antibody testing, hemoglobin electrophoresis or Hb analysis, and genetic testing (for definitive diagnosis and carrier determination)
  • Cardiac and liver MRI (T2*): Assessment of iron overload
• Information to tell the doctor in advance during an outpatient visit
  • Recent transfusion history and transfusion reactions, whether you are currently taking a chelator, whether you have undergone splenectomy, and pregnancy plans

Examples of General Questions to Ask the Doctor

• "Based on my current condition and test results, what treatment is recommended (transfusion frequency and iron chelation targets)?"
• "What are the advantages, disadvantages, and side effects of each chelator (for example, deferasirox, deferiprone, and deferoxamine)?"
• "What is the long-term prognosis of my disease, and what should be prioritized to reduce complications?"
• "What are the indications and risks of surgery (splenectomy) or bone marrow transplantation?"

Examples of Disease-Specific Questions

• "In my case (or my child's case), how do we determine whether the disease is transfusion-dependent, and what typical Hb level should be maintained?"
• "When the ferritin or cardiac MRI (T2*) results reach a particular level, what chelation strategy (choice of medication, dosage, and monitoring tests) would you recommend?"
• (For carriers) "What tests would you recommend for genetic counseling and family planning (pre-pregnancy testing and carrier testing)?"

(Note: The information above is a summary based on standard clinical guidelines and general evidence. Individual treatment, testing, and prognosis vary depending on age, genotype, transfusion history, and organ status, so an individualized plan should be established through outpatient and specialist consultation.)