Delayed hemolytic transfusion reactions in sickle cell disease: simultaneous destruction of recipients' red cells

Bystander hemolysis may be defined as the destruction of antigen-negative red cells during immune hemolysis, such as delayed hemolytic transfusion reaction (DHTR). Although many have suspected that bystander hemolysis does occur, that phenomenon is very difficult to document.

Five patients with sickle cell disease (SCD) who underwent exchange transfusion and subsequently experienced a DHTR were retrospectively evaluated. Serial samples were examined for complete blood counts, the percentage of hemoglobin A and S, and the percentage of reticulocytes. The total red cell count and the percentage of hemoglobin S were used to calculate the hemoglobin S red cell count. The patients' profiles were compared to proposed models.

DHTRs due to anti-E, -S, -Fy(a), or -Jk(a) or serologically undetectable antibodies were identified 7 to 19 days after exchange transfusion. All patients had a significant decrease in hemoglobin A red cells; 56.4 to 94.7 percent of hemoglobin A red cells were hemolyzed. Patients 4 and 5 had a decrease in hemoglobin S red cells which indicated the destruction of autologous red cells during DHTR. The evidence for bystander hemolysis was particularly convincing in Patient 5, because there was a substantial decrease in hemoglobin S red cells despite a reticulocyte production index of 2.2 percent at the nadir of the DHTR.

Hemoglobin S provides a biologic marker for monitoring autologous red cell loss in sickle cell patients. We have shown one patient with clinical evidence of bystander hemolysis complicating a DHTR.