Minimising Transfusion Therapy and Alloimmunisation in Patients with Sickle Cell Disorder in the Era of Hydroxyurea

In the UK, 700 patients with sickle cell disease are on a transfusion programme¹. Red blood cell (RBC) AI occurs in 4.4-76%² of regularly transfused sickle patients. Contributing factors include repeated transfusions and ethnic differences between sickle cell patients and their donors. This results in higher rates of mismatch in phenotyped and genotyped blood. There is a continued lack of availability of blood products from more compatible ethnic donors.

Sickle patients on transfusion programmes are transfused every 3-6 weeks, creating a large burden on healthcare services in terms of time, labour and resources such as extended red cell typing in order to reduce antibody formation. The presence of RBC antibodies in patients can cause significant delays in obtaining cross matched blood and reductions in phenotype matched blood being transfused.

The aims of this project were to a) review transfusion use in relation to the use of hydroxyurea (HU) patients treated at Alder Hey (AH) and b) review rates of AI in these patients. At AH we have changed our practice to offer HU from age 9 months as a disease modifying therapy 20-35mg/kg/day.

We retrospectively reviewed the use of blood products in our cohort of 60 patients, age between 0-20 years (mean 11yrs). Patients were observed over their life period treated at AH, mean 10.1 patient years, range 0-20years, total of 439 patient years. We studied retrospectively the number of RBC transfusions and the historical presence of antibodies. We then re-tested all patients to determine current antibody status.

Prior to commencement of hydroxyurea, 342 units of bloods were transfused to 21 patients over 243 patient years, which is 1.41 units per patient per year.

After commencement of hydroxyurea, 114.5 units were transfused to 17 patients in 187.1 patient years, 0.61 units per patient per year.

Indications for transfusion included acute chest syndrome, aplastic crisis, prolonged crisis, increased acute anaemia, hydroxyurea induced anaemia, pre-operatively.

3 patients in our cohort had previous antibodies. Upon repeat antibody screening, no patients had detectable RBC antibodies.

All patients have an extended red cell phenotype as part of their initial workup on referral to our service. Elective, non-acute patients (transfusion programme, pre-operative, hydroxycarbamide induced anaemia) all receive fully phenotyped blood. This cannot be guaranteed in acute situations where patients receive the best matched blood available.

This practice of minimising blood transfusion use in patients with sickle cell anaemia can reduce blood product usage and as a result reduce the demand for ethnic minority transfusion donors. The subsequent donor exposure would therefore also decrease transfusion related complication of AI.

¹ National Haemoglobinopathy Registry Annual Report 2016/17

²G. da Cunha Gomes, E & A. F. Machado, L & C. de Oliveira, L & F. N. Neto, J. (2018). The erythrocyte alloimmunisation in patients with sickle cell anaemia: a systematic review: Erythrocyte alloimmunisation in sickle cell anaemia. Transfusion Medicine. 10.1111/tme.12543.