Alloimmunization and hyperhemolysis in sickle cell disease

Abstract

Alloimmunization against red blood cell antigens and delayed hemolytic transfusion reaction (DHTR) are major barriers to transfusion in sickle cell disease (SCD). In SCD, DHTR is a potentially life-threatening. Blood group polymorphism in SCD patients, who are of African ancestry and frequently exposed to antigens they do not carry; an inflammatory clinical state; and occasional transfusion in acute situations are risk factors for alloimmunization and DHTR. In patients at risk, the transfusion indication must be balanced against the risk of developing DHTR. However, when transfusion is absolutely necessary, protocols combining the prevention of exposure to immunogenic antigens with immunosuppressive treatments must be implemented, and patients should be carefully monitored during posttransfusion follow-up. This close monitoring makes it possible to diagnose hyperhemolysis as soon as possible; to avoid retransfusion, which can exacerbate hemolysis; and to administer specific treatments, such as anticomplement therapy, in severe cases. Finally, in patients with severe disease, hematopoietic stem cell transplantation may be indicated. However, transfusion is also required in this context, and its management is complex because these risks must be taken into account.

Graphical abstract

Figure 1.

Decision making process for the indication of transfusion in a patient with history of hyperhemolysis. A patient with history of posttransfusion hyperhemolysis is at risk for recurrence of the syndrome, with or without detectable antibodies. When a transfusion is indicated, a shared decision-making process assesses the risk/benefit of transfusion, and if maintained, establishes the transfusion protocols in terms of RBC antigen matching and the use of immunosuppressive therapy. Close monitoring of the posttransfusion phase is absolutely necessary, and assessment of total Hb and HbA% immediately after transfusion will help diagnose posttransfusion hyperhemolysis with new assessment of these parameters. If clinical signs appear, evaluation of hemolytic biological parameters and an IH workup are performed. A negative IH workup does not rule out the diagnosis. After confirmation of hyperhemolysis, supportive care and specific treatments are considered. Hb, hemoglobin; IH, immunohematology; LDH, lactate dehydrogenase; RBC, red blood cell; VOC, vaso-occlusive crisis.