Incidence and predictive score for delayed hemolytic transfusion reaction in adult patients with sickle cell disease

Abstract

Delayed hemolytic transfusion reaction (DHTR) is a life-threatening complication of transfusion in sickle cell disease (SCD). The frequency of DHTR is underestimated because its symptoms mimic those of vaso-occlusive crisis and antibodies (Abs) are often not detectable. No predictive factors for identifying patients likely to develop DHTR have yet been defined. We conducted a prospective single-center observational study over 30 months in adult sickle cell patients. We included 694 transfusion episodes (TEs) in 311 patients, divided into occasional TEs (OTEs: 360) and chronic transfusion program (CTEs: 334). During follow-up, 15 cases of DHTR were recorded, exclusively after OTEs. DHTR incidence was 4.2% per OTE (95% CI [2.6; 6.9]) and 6.8% per patient during the 30 months of the study (95% CI [4.2; 11.3]). We studied 11 additional DHTR cases, to construct a predictive score for DHTR. The DHTR mortality is high, 3 (11.5%) of the 26 DHTR patients died. The variables retained in the multivariate model were history of DHTR, number of units previously transfused and immunization status before transfusion. The resulting DHTR-predictive score had an area under the ROC curve of 0.850 [95% CI: 0.780-0.930], a negative-predictive value of 98.4% and a positive-predictive value of 50%. We report in our study population, for the first time, the incidence of DHTR, and, its occurrence exclusively in occasionally transfused patients. We also describe a simple score for predicting DHTR in patients undergoing occasional transfusion, to facilitate the management of blood transfusion in SCD patients.

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

“…Previous reports have shown that complement activation most likely from the alternative pathway may be involved in the pathogenesis of DHTRs with hyperhemolysis in SCD patients with no identifiable alloantibody . However, it should be noted that some patients who experience DHTRs experience full recovery to baseline Hb levels without any specific immunosuppressive intervention …”

“…These recommendations, however, would need to be tested prospectively to definitively demonstrate their efficacy at preventing or treating DHTRs. Given the appreciable rate of DHTRs coupled with the potentially devastating consequences that can ensue, additional mechanistic studies are critically needed to determine optimal treatment options for this vulnerable patient population.…”

“…In addition, alloimmunized patients are particularly prone to developing severe delayed hemolytic transfusion reactions (DHTRs), serious immune‐mediated complications that can occur following an RBC transfusion that can contribute to premature death . By adulthood, patients with SCD have often received many RBC transfusions and therefore are at increased risk for developing DHTRs, with a reported incidence of 4.8% to 7.7% and a rate of 3.5 to 4.2 DHTRs per 100 episodic transfusions . DHTRs can occur up to 3 weeks following an RBC transfusion and are frequently missed in this population because the presenting symptoms can mimic a vaso‐occlusive crisis (VOC), a common complication of SCD.…”

Health literacy and knowledge of chronic transfusion therapy in adolescents with sickle cell disease and caregivers

“…There is a strong need for additional educational resources for patients and caregivers with SCD receiving transfusion therapy, with focus on transfusion benefits, adverse reactions, and the importance of keeping a personal record of transfusion episodes and reactions. This education is of particular importance to those receiving episodic transfusion therapy as well as CTT, as delayed hemolytic transfusion reactions occur more frequently in episodically transfused patients with SCD and may be under‐recognized or misdiagnosed …”

Sickle Cell Disease Complicated by Iron Overload: An Under-Recognized Risk Factor for <b><i>Vibrio vulnificus</i></b> Infection

“…Patients with sickle cell disease (SCD) often receive unnecessary red blood cell (RBC) transfusions leading to complications which include alloimmunization, hyperhemolysis, and iron overload [1-3]. An under-recognized risk of iatrogenic iron overload in patients with SCD is an increased susceptibility to infections with siderophilic, or “iron-loving,” bacteria.…”