Appropriate Management/ Monitoring

The administration of RBC transfusions is common in both children and adults with SCD. In this area, the expert panel reviewed literature to answer questions about phenotype matching, the goals of transfusion therapy, and appropriate monitoring in chronically transfused individuals. Studies have tried to answer whether giving phenotypically matched red cells decreases the risk of alloimmunization in people with SCD. In addition, questions have arisen about the appropriate transfusion goals for patients undergoing transfusion both acutely and chronically. The expert panel was able to make recommendations for goals of chronic transfusion therapy in children, but evidence was insufficient to propose a goal HbS concentration for chronically transfused adults, as it may vary by indication.

This section concludes with a consensus-based protocol on appropriate monitoring of patients who receive chronic transfusions. The protocol contains several technical remarks and recommendations needed to implement chronic transfusion therapy safely and effectively. The protocol should be considered as guidance and modified to fit an individual patient’s clinical situation.

Phenotype Matching
Four RCTs, 63 longitudinal and cross-sectional studies, and 46 case reports were identified that demonstrated alloimmunization. In the four RCTs (with>1,100 patients), alloimmunization/autoimmunization development rates ranged between 3 percent and 29 percent. In the other 63 studies (involving >6,000 patients), alloimmunization rates ranged between 6 percent and 85 percent, and autoimmunization rates ranged between 4 percent and 10 percent. Overall, minimal evidence is available to support a particular method to reduce or prevent side effects from RBC transfusion.

The systematic review did not identify comparative effectiveness studies that explored different cross-matching approaches. Two studies (one RCT and one observational study involving 159 patients) that implemented stricter matching criteria had more favorable results (alloimmunization rates <7 percent) The definition of a “strict cross match” varied among studies, and often included matching for ABO and a number of other RBC antigens, including DCcEe and Kell, and occasionally Kidd and Duffy. In the published studies, to prevent alloimmunization or to transfuse patients who were already alloimmunized, investigators most commonly opted to use strictly phenotype-matched RBC units. Transfusion Goals The systematic review did not identify evidence supporting the effectiveness of a specific HbS percentage cutoff for transfusion (i.e., there are no comparative studies in which different HbS targets were evaluated). In the transfusion protocols used in the included randomized trials of patients treated with chronic transfusion, two (both in children) used a cutoff of :30 percent (STOP 1 and 2), while the remaining trial, which studied the use of chronic transfusion in pregnancy, used a cutoff of hemoglobin between 10 g/dL and 11 g/dL405 and a HbS cutoff of :35 percent. The :30 percent cutoff was used in roughly 75 percent of the observational studies (a total of 2,648 adults and 4,523 children).

However, it is unclear how the use of these cutoffs correlates with outcomes. In the two multicenter stroke prevention trials, this cutoff was beneficial in reducing the risk of stroke (compared to no transfusion). These data may guide the practice of transfusion in SCD and suggest a particular transfusion goal; however, the evidence is indirect and of low quality. No studies evaluated the effectiveness of different monitoring strategies. Recommendations RBC units that are to be transfused to individualswith SCD should include matching for C, E,and K antigens. (Moderate Recommendation, Low-Quality Evidence) In patients with SCA, who are not chronically transfused and who are therefore at risk for hyperviscosity due tohigh percentages of circulating HbS-containing erythrocytes,avoid transfusing to a target hemoglobin above 10 g/dl. (Moderate Recommendation, Low-Quality Evidence) In chronically transfused children with SCA, the goal of transfusion should be to maintain a HbS levelof below 30 percent immediately prior to the next transfusion. (Moderate Recommendation, Moderate-Quality Evidence) The expert panel recommends that clinicians prescribing chronic transfusion therapy follow an establishedmonitoring protocol. (Moderate Recommendation, Low-Quality Evidence) Although the literature does not offer evidence comparing different implementation protocols for chronic transfusion therapy, the expert panel was concerned about inadequate monitoring if a protocol is not used. Hence, talcing into account the evidence supporting the use of routine monitoring, the expert panel issued a recommendation for adopting a standardized protocol to maximize benefits and safety. A suggested protocol was developed by the expert panel based on (1) protocols used in the published clinical trials and observational studies, (2) indirect evidence derived from basic science, and (3) a consensus process. The protocol contains several technical remarks and recommendations needed to implement chronic transfusion therapy safely and effectively, but the protocol should be considered as guidance and modified to fit an individual patient’s clinical situation.