The cause and pathogenesis of hemolytic transfusion reactions in sickle-cell disease

The current review aims to summarize the epidemiology, cause, pathophysiology, and management of hemolytic transfusion reactions in sickle-cell disease (SCD).

Patients undergoing occasional, isolated transfusions have been shown to have a higher risk of developing this condition. Despite the identification of well known risk factors, including alloimmunization, the pathophysiology of this syndrome remains unclear, as very severe forms with hyperhemolysis may develop in the absence of detectable antibodies, or with antibodies that are not considered to be clinically significant. Complement plays a crucial role in this reaction, particularly in cases of intravascular hemolysis. Complement triggers the reaction, but it also amplifies the inflammatory response and aggravates tissue damage. Free heme and hemoglobin are released and interact with complement, causing tissue damage.

Hemolytic transfusion reactions are the most feared complications of blood transfusion in patients with SCD. This reaction is underdiagnosed because it mimics a vaso-occlusive crisis. Alloimmunization against red blood cell antigens is known to be a major trigger of this reaction, but abnormal complement activation and the underlying condition in patients with chronic hemolysis, may amplify the reaction. There is an urgent need to develop evidence-based approaches for preventing and treating this reaction.