How we treat delayed haemolytic transfusion reactions in patients with sickle cell disease

Abstract

SummaryTransfusion therapy is effective in the prevention and treatment of many complications of sickle cell disease (SCD). However, its benefits must be balanced against its risks, including delayed haemolytic transfusion reactions (DHTR). Not only is the relative rate of alloimmunization higher in patients with SCD than in other patient populations, but attendant risks associated with DHTR are even greater in SCD. Clinicians' awareness of DHTR events is poor because symptoms of DHTR mimic acute vaso-occlusive pain and immunohaematology findings are often negative. Transfusions delivered in the acute rather than elective setting appear to confer a higher risk of DHTR. Management of DHTR in SCD depends on the clinical severity, ranging from supportive care to immunosuppression, and optimization of erythropoiesis. DHTR must be considered in any recently transfused patient presenting with acute sickle cell pain. Meticulous documentation of transfusion and immunohaematology history is key. We anticipate an increase in DHTR events in SCD patients with the increasing use of red blood cell transfusion therapy.

Fatal delayed haemolytic transfusion reaction in a patient without previous transfusions but with an obstetric history of 13 pregnancies

“…However, the extremely low haemoglobin levels, lower than the pretransfusion levels, indicated that extensive haemolysis including both donor and recipient cells had occurred. This subset of DHTR has been described by some as hyperhaemolytic transfusion reaction and ‘hyperhaemolysis’ syndrome 11. Furthermore, while reticulocytosis is normally a hallmark of haemolytic reactions, reticulocytopenia, as seen in this case, has been a well-documented manifestation of hyperhaemolysis 12 13…”

“…The exact mechanisms responsible for this extensive haemolysis have not been entirely elucidated. One potential reason for the autologous RBC destruction in these patients is the formation of a non-specific antibody that binds complement and destroys both donor and recipient red cells, known as bystander haemolysis 11. Another possible explanation is a hyperactive phagocytic activity of macrophages where a sudden high titre of antibodies leads to destruction of donor cells leading to cytokine release and reactive oxygen radicals that may damage autologous cells 13.…”

“…Another possible explanation is a hyperactive phagocytic activity of macrophages where a sudden high titre of antibodies leads to destruction of donor cells leading to cytokine release and reactive oxygen radicals that may damage autologous cells 13. Other possible mechanisms that have been suggested to play a role include human leucocyte antigen antibody formation, suppression of erythropoiesis and excessive eryptosis 11. In addition, it is likely that the patient’s pre-existing renal dysfunction may have played a role in this catastrophic outcome, as the patient’s renal function worsened very rapidly with severe metabolic acidosis.…”

Challenges in the treatment and prevention of delayed hemolytic transfusion reactions with hyperhemolysis in sickle cell disease patients

“…As the prediction and prevention of DHTRs in patients with SCD remains a significant clinical challenge, efforts to develop immunosuppressive therapy–based approaches to prevent and/or treat ongoing DHTRs has become a primary focus in the management of transfusion complications in patients with SCD. Several approaches directed at potentially preventing or reducing the consequences of alloantibody‐mediated RBC removal in the setting of an active DHTR or when a DHTR appears likely include steroid‐induced immune suppression and IVIG . In some reported cases, patients have demonstrated an improvement following treatment with either IVIG alone or in combination with corticosteroids; however, some patients required further immunosuppression before recovery .…”

Transfusion as an Inflammation Hit: Knowns and Unknowns

“…Another population of patients benefiting from frequent transfusion episodes, sickle-cell disease patients, led to an important discovery: first, they manifest complex hemolytic reactions that involve activated complement and present as essentially inflammatory (25) and second, they are subjected to the most frequent rate of alloimmunization among tracked cohorts of transfused patients (26). This prompted specialists to also examine the inflammatory potential of stored erythrocytes.…”