Tocilizumab in the management of posttransfusion hyperhemolysis syndrome in sickle cell disease: The experience so far.

BACKGROUND: Posttransfusion hyperhemolysis syndrome is a rare but life-threatening form of delayed hemolytic transfusion reaction with lysis of both transfused and autologous red cells, seen predominantly in patients with sickle cell disease. Macrophage activation is thought to play a major role in its pathophysiology. Standard treatment is with intravenous immunoglobulin and steroids but refractory cases pose a major clinical problem. Tocilizumab is a humanized monoclonal antibody against the IL-6 receptor that can inhibit IL-6 induced macrophage activation. METHODS AND MATERIALS: We describe the case of a 33-year-old woman with sickle cell anemia and posttransfusion hyper hemolysis syndrome refractory to standard therapy, treated with Tocilizumab. We also review all cases reported in the literature where Tocilizumab was used for posttransfusion hyperhemolysis. RESULTS: Treatment with Tocilizumab was well tolerated with no observed adverse events. There was no further drop in Hb after day 2 of treatment with subsequent continuous gradual improvement. Her bilirubin dropped significantly after the first dose and continued to improve, while ferritin and LDH reduced significantly after day 2 of treatment with Tocilizumab and continued to drop thereafter. Like in our case, all other cases in the literature where Tocilizumab was used for posttransfusion hyperhemolysis led to rapid clinical responses and no adverse events. DISCUSSION: Even though the number of cases of posttransfusion hyper hemolysis syndrome treated with Tocilizumab are few, they have all been associated with rapid clinical responses with no observed adverse events suggesting that the role of Tocilizumab in this context needs to be further explored.

Automated Red Cell Exchange in the Management of Sickle Cell Disease.

Red cell transfusion represents one of the cornerstones of the chronic management of sickle cell disease, as well as its acute complications. Automated red cell exchange can rapidly lower the number of circulating sickle erythrocytes, without causing iron overload. Here, we describe our experience, having offered this intervention since 2011. A transient reduction in the platelet count by 61% was observed after the procedure. This was not associated with any haemorrhagic complications. Despite exposure to large volumes of blood, the alloimmunisation rate was only 0.027/100 units of red cells. The absence of any iron loading was confirmed by serial Ferriscans, performed over a number of years. However, patients with advanced chronic kidney disease showed evidence of iron loading due to reduced innate haemopoiesis and were subsequently switched to simple transfusions. A total of 59% of patients were on regular automated red cell exchange with a history of recurrent painful crises. A total of 77% responded clinically, as evidenced by at least a 25% reduction in their emergency hospital attendance for pain management. The clinical response was gradual and increased the longer patients stayed on the program. The earliest sign of clinical response was a reduction in the length of stay when these patients were hospitalised, indicating that a reduction in the severity of crises precedes the reduction in their frequency. Automated red cell exchange also appeared to be beneficial for patients with recurrent leg ulcers and severe, drug resistant stuttering priapism, while patients with pulmonary hypertension showed a dramatic improvement in their symptoms as well as echocardiographic parameters.