LAUSR

Post-transfusion hyperhaemolysis syndrome (PTHS) is a rare post-transfusion reaction seen primarily in patients with sickle cell disease (SCD). It is characterised by brisk haemolysis of both transfused and recipient red cells, also known as ‘By-stander’ haemolysis, with a haemoglobin (Hb) drop below pre-transfusion levels, marked increase in serum ferritin (SF) and a fall in reticulocyte count. This is a potentially life-threatening complication as it can lead to severe anaemia while further transfusion may further aggravate haemolysis and should only be used as a last resort (Win 2019). The pathophysiology of PTHS is still poorly understood. ‘By-stander’ haemolysis, which is probably complement mediated, and suppression of erythropoiesis have been implicated while there is increasing evidence that macrophage activation and direct haemophagocytosis plays a key role (Win et al, 2019). Standard treatment in severe cases is with intravenous immunoglobulin (IVIG) 0 4 g/day for five days and high dose steroids (intravenous methylprednisolone 0 5 g/day for two days) (Win et al, 2008). Tociluzimab is a humanised monoclonal antibody against soluble and membrane bound interleukin 6receptor (IL6R). The binding of tociluzimab to IL6R prevents the cytokine IL6 from exerting its pro-inflammatory effect. It is currently approved for the treatment of various autoimmune conditions, such as rheumatoid arthritis, systemic juvenile idiopathic arthritis and giant cell arteritis (https:// www.nice.org.uk/guidance/ta247, https://www.nice.org.uk/ guidance/ta238, https://www.nice.org.uk/guidance/TA518) and has been successfully used in the management of macrophage activation syndrome (Watanabe et al, 2016). In PTHS the hypothesis is that macrophage activation results in phagocytosis of patient and donor reticulocytes and mature red blood cells. There is some anecdotal evidence that tociluzimab may have a potential role in the management of PTHS, especially when resistant to standard measures, none of which has been published as a peer reviewed paper (Lee et al, 2018). We report a case of PTHS treated with tociluzimab in a 33-year-old man with homozygous sickle cell disease (HbSS). The patient had a history of recurrent episodes of the acute chest syndrome (ACS) and also two previous episodes of PTHS following exchange transfusion for treatment of ACS. He was on treatment with hydroxycarbamide, varying from 1 5 to 2 0 g/day, for ACS prevention, but compliance was poor. On this occasion, he was admitted to hospital with a painful crisis accompanied by type I respiratory failure and diffuse bilateral chest x-ray infiltrates, diagnostic of a new episode of ACS. He received an emergency automated red cell exchange transfusion (ARCET) with 12 units of red cells. His haemoglobin (Hb) and HbS percentage preand postARCET were 63 g/l and 93% and 120 g/l and 26% respectively. Because of the previous two episodes of PTHS he was preemptively treated with IVIG 0 4 g/kg/day for five days and methyprednisolone 500 mg for 3 days, both commencing on the day of the exchange transfusion. Despite this, his Hb dropped sharply, from 97 g/l on Day 5 post-ARCET to 4 7 g/l on Day 8, and his haemolytic markers, such as bilirubin and lactate dehydrogenase (LDH), started increasing as did his serum ferritin. He had no detectable allo-antibodies and his direct antiglobulin test was negative. His Hb continued to drop (nadir 32 g/l on Day 12 post-ARCET). As he had been nursed in the intensive care unit from the beginning of his admission, ensuring very close monitoring, further transfusion was withheld with a view to be undertaken immediately as soon as he displayed any signs of haemodynamic compromise. Instead, he was treated with tocilizumab 8 mg/ kg intravenously once daily for two days, which was not associated with any adverse reactions. The patient’s urine, previously deeply discoloured, appeared clear the morning after the first dose of tocilizumab. On day 2 after starting treatment with tocilizumab, his reticulocytes had increased, from 128 9 10/l to 414 9 10/l, SF had decreased, from 18 342 to 9923 μg/l, and his haemolytic markers immediately started to improve (Fig 1). There was no further drop in his Hb. His serum IL6 level measured before treatment was 140 pg/ml (reference range <7 pg/ml), which rose to 1400 pg/ml after the first dose and 3870 pg/ml after the second dose. We assume these results reflect effective blockade of the IL6R with subsequent increase in unbound circulating IL6. The time for Hb recovery from its nadir value to the patient’s baseline was not shorter than the previous two episodes of PTHS suffered by this patient. However, it should be noted that haematological and biochemical parameters Correspondence