Introduction:

• Criteria for diagnosis- Ability to maintain hemoglobin level compatible with comfortable survival in the absence of regular transfusions.
• Most of them maintain hemoglobin at 6gm/dL without transfusions
• HbF is usually 10-50%. May be up to 100% and HbA2 is >3.5%
• Later they may become transfusion dependent especially due to progressive splenomegaly.

Clinical features:

• Usually present at 2-6 years
• Usually have retarded growth and development. But some are asymptomatic
• Deformities of bone and face, due to increased erythropoiesis
• Osteoporosis and pathological fractures are common
• Moderate to severe splenomegaly
• Sometimes hepatomegaly
• Thrombosis and pulmonary hypertension are more common than beta thalassemia major.
• May have leg ulcers
• Hemosiderosis secondary to increased intestinal iron absorption is often present

Genotypes seen in these patients include:

• β⁰ /β 
• β⁺ /β⁺
• ^β+ /β+ 
• β⁺ with alpha thalassemia trait  or β⁺ with HbH
• β⁰/β⁰ with heterocellular HPFH
• HbE/ β thalassemia (they have remarkable capacity to adopt to low hemoglobin. Transfusion should be given generally if Hb is <5gm/dL)
• XmnI polymorphism
• Alpha thalassemia intermedia (Hemoglobin H disease)
• Delta beta thalassemia
• Beta thalassemia lepore

Treatment:

• Folic acid- 5mg- OD
• Closely observe these patients for first few years of life. Assess growth and development.
  • Normal development- Maintain without transfusions
  • Growth is affected / Face changes/ Severe osteoporosis/ splenomegaly/ extramedullary masses- Start regular transfusion regimen and chelation, as done for thalassemia major. Reassess regularly and withdraw when sustained clinical benefit is achieved.
• Cap. Hydroxyurea- 5-10mg/Kg- Increase dose by 3-5mg/kg/day every 8 weeks, maintaining ANC >2000/cmm. If no rise in Hb by 1gm after 6 months of therapy, stop hydroxyurea.
• Chelation may be needed even in absence of regular transfusions.
• Splenectomy: 
  • Done after child grows older. 
  • It increases hemoglobin by 1-3gm/dL. 
  • Indications:
    • Worsening anemia leading to poor growth and development
    • Situation when transfusion therapy is not possible or iron chelation is not available.
    • Hypersplenism leading to problematic cytopenia.
    • Symptomatic splenomegaly
    • Massive splenomegaly with concerns about splenic rupture.
• Other drugs which are tried:
  • Thalidomide: Used in patients who are transfusin dependent and show no response to hydroxyurea.

Special situations:

• Pregnancy:
  • Explain the risk of having affected child and need for prenatal diagnosis and high risk nature of pregnancy.
  • Discontinue iron chelators and hydroxyurea.
  • Give phenotype matched PRBC with target Hb 9gm%
  • Aspirin to be given throughout pregnancy.
  • Peripartum thromboprophylaxis is must with LMWH.