Red blood cell alloimmunization is influenced by recipient inflammatory state at time of transfusion in patients with sickle cell disease

Abstract

SummarySickle cell disease (SCD) patients are at increased risk of red blood cell (RBC) alloimmunization. Recipient inflammatory state at time of transfusion has been shown to regulate alloimmunization in murine models, but evidence is lacking in SCD patients. We retrospectively studied a cohort of alloimmunized SCD patients to determine the influence of pro-inflammatory SCD-related complications at time of transfusion on alloimmunization. For each transfusion, the presence of pro-inflammatory state, degree of RBC antigen matching, unit age, storage solution and alloantibody detection date were ascertained. Transfusion-associated pro-inflammatory events were compared between transfusions resulting and not resulting in new alloantibodies. Univariate analysis and multivariate logistic regression were performed. Fifty-two patients received 3166 pre-storage leuco-reduced transfusions of which 128 resulted in alloantibodies. Transfusions during inflammatory events were associated with increased alloantibody risk on univariate and multivariate analysis; acute chest syndrome and vaso-occlusive crisis showed strongest associations with alloimmunization. Increased antigen matching demonstrated a protective effect on alloimmunization (univariate and multivariate analysis). Although an association was seen between citrate-phosphate-dextrose (adenine) stored units and alloimmunization on univariate analysis, no effect was found on multivariate analysis. Identifying recipient pro-inflammatory states at time of transfusion that promote alloimmunization can impact RBC unit selection decisions for SCD patients at risk for alloimmunization.

Prophylactic transfusion for pregnant women with sickle cell disease: a systematic review and meta-analysis

“…A recent study found that the proinflammatory state characteristic of SCD-related challenges, when present at the time of transfusion, was associated with an increased risk of alloimmunization, with acute chest syndrome and vaso-occlusive episodes demonstrating the strongest relationship with alloantibody formation. 35 Although this finding needs replication in prospective studies, it may lend further credence to a preemptive approach aimed at preventing the need for transfusion in the acute setting.…”

Early occurrence of red blood cell alloimmunization in patients with sickle cell disease

“…The observed difference may have been underestimated as the interval between transfusion and antibody screening was much larger in the episodic group and under detection of antibodies due to evanescence may have occurred [49,50]. In general, episodic transfusions are often given for treatment of acute pro-inflammatory complications such as an acute chest syndrome, or hemolytic or vasoocclusive crises [3,24,51]. The higher alloimmunization risk associated with episodic transfusions adds to the notion that RBC units given during acute, inflammatory events are associated with an increased risk for alloimmunization [24,52,53].…”

“…In general, episodic transfusions are often given for treatment of acute pro-inflammatory complications such as an acute chest syndrome, or hemolytic or vasoocclusive crises [3,24,51]. The higher alloimmunization risk associated with episodic transfusions adds to the notion that RBC units given during acute, inflammatory events are associated with an increased risk for alloimmunization [24,52,53].…”

Red blood cell alloimmunization is influenced by the delay between Toll-like receptor agonist injection and transfusion

“…However, in SCD patients, a recent study showed that an inflammatory state at the time of transfusion, independently of direct TLR stimulation, can influence RBC alloimmunization. 24 The underlying inflammatory state of the patient and TLR signaling may, therefore, be central to the process of RBC alloimmunization.…”