There are many exciting new therapies for SCD, and work is ongoing to develop and improve curative therapies. However, red blood cell transfusion is, and will continue to be, a therapeutic mainstay for complications of SCD, and this is true in both acute and chronic settings. Most patients with SCD will receive at least 1 transfusion by the time they reach adulthood; however, we all need to be judicious in choosing transfusion only when there is good evidence that it is indicated.

The main complications that we have observed from transfusion are iron overload and alloimmunization, both of which can be prevented to a certain degree and both of which have benefited from recent efforts to issue practice guidelines and raise awareness.

We now have several iron chelation therapies that can prevent iron overload, including oral agents. Previously, the only option had been a slow (eg, overnight) subcutaneous infusion. Still, a subset of patients do not tolerate oral chelation well or may not be 100% compliant, so significant iron overload among those who require chronic transfusion (eg, monthly) remains a common problem.

In the area of alloimmunization, we have come a long way in identifying patients with SCD who have certain red cell antigen phenotypes that we know put them at increased risk. All patients with SCD should receive prophylactic antigen-matched red blood cells for C, E, and K antigens. Implementation of this practice has significantly decreased alloimmunization. Unfortunately, alloimmunization persists, in part due to antigens outside the Rh system and K (Kell blood group system). Increasingly, we use red blood cell genotyping to predict antigen phenotypes and to better match for additional antigens that we identify in high-risk patients. High-risk individuals include those who already have formed multiple alloantibodies or who express partial Rh antigens despite typing positive for that antigen (ie, the patient is C positive, but RH genotype predicts partial C antigen expression). Red blood cell genotyping is commercially available, and specific testing platforms are US Food and Drug Administration approved. Despite serologic Rh matching, patients with SCD continue to make antibodies against Rh antigens. Thus, we hope that the RH genotyping of patients and donors can become more cost-effective and broadly available so that in the future it can be adopted by all centers that care for patients with SCD.

I am very optimistic that we are making progress in closing the gap. This was part of the mission of the 2020 American Society of Hematology guidelines on transfusion support in SCD, which highlighted the need to provide prophylactic Rh and K antigen matching for all patients with SCD.

It is also important that patients and providers remain vigilant for the signs and symptoms of hemolysis above their baseline with SCD (eg, more jaundice, more scleral icterus, and darker urine). When patients present with pain in these scenarios, a delayed hemolytic transfusion reaction should be on the differential if they have recently been transfused, as these reactions can be mistaken for a vaso-occlusive crisis.