3.6 Red blood cell transfusion in chronically transfused patients

3.6.1 Thalassaemia

Evidence Statements for Thalassaemia
Evidence Statements –
Evidence Consistency Clinical impact Generalisability Applicability
ES6.1 In patients with thalassaemia, the effect of the pretransfusion Hb threshold on mortality is uncertain. X NA X
ES6.2 In patients with thalassaemia, a pretransfusion Hb concentration of 90 – 100 g/L may reduce transfusion volume, compared with 100 – 120 g/L.

ES, evidence statement; Hb, haemoglobin

=A; =B; =C; X=D; NA,not applicable (see Table 2.1)

Practice Point – Thalassaemia
PP23 In patients with thalassaemia, the evidence does not support any change to the current practice of maintaining a pretransfusion Hb concentration of 90 – 100 g/L, with transfusions at about monthly intervals.

Hb, haemoglobin; PP, practice point

The use of chronic RBC transfusions intensified in 1978, when iron chelation therapy using subcutaneous desferrioxamine infusions was introduced to improve the management of iron overload in ß thalassaemia major. The aim of the transfusions was to prevent severe anaemia and early mortality and to promote growth, development, well-being and quality of life. They were also intended to minimise or prevent the expansion of the marrow mass that leads to bone deformities such as maxillary hyperplasia and extra medullary haematopoietic tissue, which typically occur in liver and spleen and along the vertebral column.

The appearance of any of these complications in infancy and childhood is used as a trigger to commence blood transfusion treatment, with the widely accepted aim of maintaining a pretransfusion Hb concentration of at least 90 – 110 g/L, and a mean of approximately 120 g/L. This pretransfusion Hb concentration was adopted empirically, after trials of lower levels found that some of the complications from under-transfusion (e.g. bone marrow expansion) continued to appear. Hence, in the late 1970s and 1980s, there was widespread adoption of the pretransfusion Hb range of 90 – 110 g/L, which was the maximum achievable with 3 – 4 weekly transfusions. To this day, this treatment is accepted as optimal when combined with adequate chelation therapy. Hypersplenism requiring splenectomy occurs in at least 50% of patients and is usually carried out when the blood transfusion requirement exceeds 200 – 250 ml/kg/year. Splenectomy usually results in a significant reduction in transfusion requirement.

In contrast to ß thalassaemia major, recent studies have reported that complications in patients with ß thalassaemia intermedia appear to be less common. This is particularly so later in life in patients undergoing regular transfusion, and is more common in patients who have undergone splenectomy. Thus, regular transfusion may become a more common option for management and prevention of complications that occur later in life in this subgroup of patients. However, the management of ß thalassaemia intermedia will continue to be personalised until more is known about these late complications.

The adequacy of blood transfusion and chelation therapy in individual treatment centres depends on the adequacy of local resources (including blood banking) and funding for an appropriate iron chelating agent. There are few studies to support this management strategy; however, patients managed in this way are now surviving into the sixth decade of life. The literature review found only a few studies that objectively addressed aspects of these management issues.

One retrospective cohort study of fair quality (Level III) provided support for the association of current pretransfusion level with longer survival.151 The study reported that subjects with a pretransfusion Hb concentration >90 g/L had significantly longer mean survival than those with a level <90 g/L.

Two prospective cohort studies (Level II)152,153 and one retrospective cohort study (Level III)154 investigated the relationship between pretransfusion Hb concentrations and transfusion volume. Cazzola154 and Masera152 found that patients maintained with a mean pretransfusion Hb concentration of 90 – 100 g/L and 102 g/L, respectively, required significantly lower transfusion volumes than patients with higher pretransfusion levels. Masera152 found that this difference was maintained for the first 5 months, after which time there was no significant difference. Cazzola154 found no differences between subgroups with or without splenectomy, and Masera152 included only splenectomised patients. Torcharus153 reported that paediatric patients with a pretransfusion Hb concentration of >80 g/L had a higher mean transfusion volume than subjects with a mean pretransfusion Hb of 60 – 70 g/L. These results support current practice.

Quality-of-life issues have been important in the optimal management of patients with transfusion- dependent ß thalassaemia major. High-quality prospective or retrospective cohort studies are required in this area.