Transfusion Practices in Thalassemia

What is thalassemia?

Thalassemias are diseases of ineffective erythropoiesis resulting from inheritance of mutated globin genes. These mutations lead to reduced or absent production of alpha or globin chains, causing ineffective erythropoiesis, of variable severity depending on the genotype and residual globin chain synthesis.

The goal of red blood cell (RBC) transfusion in patients with thalassemic defect is to correct anemia and suppress ineffective erythropoiesis, which then prevent growth delays, skeletal abnormalities and improve quality of life. RBC transfusions are not without risks which include transfusion reactions, alloimmunization, and iron overload. This population is at particularly high risk of iron overload due to their underlying disease process. Thus, RBC transfusions thresholds are different in patients with thalassemia than those without and should be carefully considered.

 It is important to keep in mind that transfusion approaches in this population may be individualized to attain goals of preventing anemia, growth delays, skeletal deformities and improving quality of life.

Below reviews general RBC transfusion practices and approaches in thalassemia.

Thalassemia are categorized into:

• Transfusion-dependent thalassemia (TDT): Generally defined as requiring regular RBC transfusion, usually 1 unit packed red blood cells (pRBCs) every 2-4 weeks
• Non–transfusion-dependent thalassemia (NTDT): Patients may require intermittent RBC transfusions below the above threshold

Goals of Transfusion Therapy:

• Correct anemia
• Reduce ineffective erythropoiesis
• Prevent growth delay and skeletal deformities
• Improve quality of life

Thalassemia Western Consortium Recommend Regular Transfusions If Either Of The Following Conditions Are Met:

• Hemoglobin <7 g/dL on ≥2 occasions at least 2 weeks apart
• β-thalassemia major: hemoglobin < 7 g/dL on ≥2 occasions, regardless of symptoms.
• Hemoglobin ≥7 g/dL, plus ≥1 severe symptoms

Sever Symptoms Include:

• Growth or puberty delay
• Skeletal facial changes
• Splenomegaly (size>6 cm or growth >1 cm/year after age 2)
• Symptomatic extramedullary hematopoiesis
• Neurologic: overt or silent Strokes, arterial narrowing, or moyamoya
• Venous thromboembolism
• Pulmonary hypertension
• Osteoporotic fractures
• Decline in functional capacity and quality of life

Target Hemoglobin Levels

• β-thalassemia major (TDT): Maintain pre-transfusion Hb > 9.5–10.5 g/dL
  • Post transfusion Hb goal : 13-15g/dL
  • These targets are designed to:
    • Limit ineffective erythropoiesis
    • Reduce the sequel of ineffective erythropoiesis
    • Minimize extramedullary hematopoiesis
    • Suppress splenic enlargement
    • Support normal growth and development

Transfusion Frequency

• Frequency depends on desired Hb and patient size (pediatric vs adult)
• Typically, 1-3 units RBCs every 2–5 weeks, individualized to maintain target pre-transfusion hemoglobin.
• Frequency should be guided by monitoring pre-transfusion hemoglobin and patient circumstances example during growth spurts  

Considerations Around Transfusion

• Iron overload:
  • Inevitable in thalassemia if TDT  due to ineffective erythropoiesis as a result of increased erythropoietin, causing suppression of hepcidin, enabling increased iron absorption 
  • Assess serum ferritin, MRI T2* of liver/heart
  • Rationale: iron overload can lead to heart failure and liver damage
• Potential complications of iron chelation:
  • Hearing loss, visual loss, cataracts, renal dysfunction, growth delay, iron deficiency and allergic reactions
    • Monitor CVC, Liver and kidney function
    • Height, weight
    • Eye exam
    • Audiogram
• Alloimmunization and hemolytic reactions:
  • Antigen match for Rh and K to minimize alloimmunization risk
• Transfusion Reactions
  • Can occur with any transfusion to any patient (with or without thalassemia)

Recommended Transfusion Approaches

• Extended RBC phenotyping or RBC genotyping prior to initiation of chronic transfusions
  • RBC genotyping * recommended
• If alloantibody present:
  • Provide antigen-negative RBC units
• Prophylactic Rh (C, E) and Kell (K) antigen matching
  • Helps reduce alloimmunization risk
  • Alloimmunization rate ranges 20-30% without prophylactic antigen matching

References

1. Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V. Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT), 3rd Edition. Thalassaemia International Federation; 2021.
2. Cappellini MD, Cohen A, Porter JB, Taher AT, Viprakasit V. Guidelines for the Management of Non Transfusion Dependent Thalassaemia (NTDT), 2nd Edition. TIF; 2017.
3. Cazzola M, Borgna-Pignatti C, De Stefano P, et al. Haematologica. 1997;82(5):558–563.
4. Singer ST, Wu V, Mignacca R, et al. Alloimmunization and erythrocyte autoimmunization in transfusion-dependent thalassemia patients of predominantly Asian descent. Blood. 2000;96(10):3369–3373.
5. Lal A, Wong T, Keel S, Pagano M, Chung J, Kamdar A, Rao L, Ikeda A, Puthenveetil G, Shah S, Yu J, Vichinsky E. The transfusion management of beta thalassemia in the United States. Transfusion. 2021 Oct;61(10):3027-3039. doi: 10.1111/trf.16640. Epub 2021 Aug 28. PMID: 34453453; PMCID: PMC9292563.
6. Overview of thalassemias: Taher AT et al. β-Thalassemias. New Engl J Med 2021;384:727-743
7. Lal A, Wong T, Keel S, Pagano M, Chung J, Kamdar A, et al. The transfusion management of beta thalassemia in the United States. Transfusion. 2021; 1–13. https://onlinelibrary.wiley.com/doi/10.1111/trf.16640
8. AABB Bulletin #23-02

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