Transfusion in Sickle Cell Disease and Thalassaemia

Transfusion in sickle cell disease and thalassaemia is lifelong for many patients and carries predictable risks: alloimmunisation, delayed haemolytic reactions, iron overload and, in sickle cell disease, hyperviscosity if haemoglobin is pushed too high. The aim differs between the two. In sickle cell disease, the aim is to improve oxygen delivery and reduce the proportion of sickle haemoglobin. In transfusion dependent thalassaemia, the aim is to suppress ineffective erythropoiesis and allow normal growth.

Alloimmunisation. Rates are high because patients receive red cells from donors of different ancestry and expressing different antigens. Phenotype matching reduces it greatly.

Risk context. Delayed haemolytic reactions with hyperhaemolysis (a life-threatening fall in haemoglobin under the pre-transfusion level), iron overload, infection, hyperviscosity and volume overload.

Special groups. Children (stroke risk), pregnancy, surgery, patients with cardiac or hepatic iron loading, and those with prior alloantibodies. In East Africa, sickle cell disease is common, blood supply is limited, family donors may carry sickle trait, and extended phenotyping and iron chelation may be unavailable, so selective use of transfusion is essential.

Sickle cell disease: when to transfuse.

• Acute stroke or transient ischaemic attack: urgent exchange transfusion where possible, aiming for haemoglobin S under 30% and haemoglobin about 10 g/dL, or simple transfusion if exchange is unavailable.

• Severe acute chest syndrome (hypoxia, worsening): simple transfusion or exchange.

• Acute splenic sequestration: small aliquots of red cells (about 5 mL/kg), cautiously, because sequestered cells may return and cause hyperviscosity.

• Aplastic crisis (parvovirus), with severe anaemia: simple transfusion.

• Symptomatic anaemia with haemoglobin well under baseline (for example a fall of over 2 g/dL from baseline, or under about 5 g/dL).

• Multi organ failure.

• Preoperative: simple transfusion to haemoglobin about 10 g/dL before moderate and high risk surgery, with exchange for the highest risk cases.

• Stroke prevention: children with abnormal transcranial Doppler (time-averaged mean velocity of 200 cm/s or more) receive regular transfusion, aiming for haemoglobin S under 30%.

Sickle cell disease: when not to transfuse. Uncomplicated pain crisis, stable chronic anaemia, and priapism as first line. Do not raise haemoglobin over 10 g/dL.

Thalassaemia.

• Transfusion dependent thalassaemia: start regular transfusion when haemoglobin is under 7 g/dL on two occasions more than 2 weeks apart (with other causes excluded), or when growth failure, bone deformity, splenomegaly or complications occur at higher haemoglobin.

• Pre-transfusion haemoglobin target about 9 to 10.5 g/dL (higher, about 11 to 12 g/dL, with cardiac disease), with transfusions every 2 to 5 weeks.

• Non-transfusion dependent thalassaemia: transfuse for specific indications (infection, pregnancy, surgery, complications).

Iron overload. Check ferritin every 3 months, liver iron concentration and cardiac iron (T2* magnetic resonance imaging) annually where available, and start chelation when ferritin is over about 1000 micrograms/L or after about 10 to 20 transfusions.

Red flags. Falling haemoglobin 3 to 14 days after transfusion with dark urine and jaundice (delayed haemolysis and hyperhaemolysis), new neurological signs, hypoxia and fever.

Product selection.

• Red cells leucodepleted, phenotype matched at least for Rh (C, c, E, e) and K, and extended matching (Kidd, Duffy, Ss) where available, with extended phenotype or genotype done before the first transfusion.

• Haemoglobin S negative units for sickle cell disease where testing exists, and sickle trait units avoided where possible. Fresh units (within about 10 days) are not required routinely.

• Antigen negative for any identified antibody.

Sickle cell disease dosing.

• Simple transfusion: red cells 10 to 15 mL/kg (about 2 units in an adult) over 3 to 4 hours, aiming to raise haemoglobin by 2 to 3 g/dL, not over 10 g/dL, and reassess.

• Exchange transfusion: manual or automated, replacing about 1 to 1.5 times the red cell volume, aiming for haemoglobin S under 30% and haemoglobin not over 10 g/dL.

• Acute chest syndrome, stroke: treat with oxygen, analgesia, antibiotics and hydration as appropriate, and transfuse by simple transfusion or exchange as indicated.

Thalassaemia dosing. Red cells 10 to 15 mL/kg (about 2 units in an adult) every 2 to 5 weeks, aiming for the pre-transfusion haemoglobin target, with a post-transfusion peak not over about 13 to 14 g/dL, each unit over 3 to 4 hours, slower in cardiac disease.

Chelation (representative doses, specialist directed). Deferasirox about 14 to 28 mg/kg daily (film-coated), deferoxamine 20 to 60 mg/kg daily by subcutaneous infusion over 8 to 12 hours on 5 or more days a week, and deferiprone 75 to 100 mg/kg daily in three doses with weekly blood counts for neutropenia. Monitor renal function, liver function, hearing and vision, and growth.

Delayed haemolysis and hyperhaemolysis. Avoid further transfusion unless life-threatening, give corticosteroid and intravenous immunoglobulin as the haematologist directs, and use erythropoietin and iron in selected cases.

Special groups.

• Pregnancy: prophylactic transfusion with matched blood in sickle cell disease with complications, with continued programme in thalassaemia.

• Surgery: preoperative transfusion plan, avoiding hypothermia, hypoxia and dehydration.

• Children: transcranial Doppler screening from age 2 where available, and hydroxycarbamide as an alternative or addition to transfusion where indicated.

Monitoring. Pre-transfusion haemoglobin and haemoglobin S, ferritin, antibody screen before each transfusion, vital signs during, and post-transfusion haemoglobin.

Complications. Alloimmunisation, delayed haemolysis and hyperhaemolysis, febrile and allergic reactions, iron overload (heart, liver, endocrine), infection, hyperviscosity and volume overload.

Referral and escalation. Haematology early, the blood bank for extended phenotyping, and cardiology and endocrinology for iron overload complications.

Disposition. Maintain a written transfusion card with phenotype, antibodies and special requirements. Plan chelation, vaccination, folate, malaria prophylaxis in sickle cell disease where appropriate, and regular follow up.