AABB22: Delayed Hemolytic Transfusion Reactions — Not So Rare?

Delayed hemolytic transfusion reactions — typically considered rare even among patients with sickle cell disease (SCD)— may actually occur more frequently among these patients, according to Sean Stowell, MD, PhD, at Sunday’s 11:15 a.m. session on “Under-Recognized Transfusion Reactions” (AM22-02-L). “These reactions are much more common than appreciated,” he said. Stowell is the medical director of apheresis at Brigham and Women's Hospital in Boston and an associate professor of pathology at Harvard Medical School.

In a study from 2017, researchers found that 4.3% of all episodic transfusions in patients with SCD resulted in a DHTR.¹ Eleven percent of patients with a DHTR died. “These data actually suggest that these are the most common transfusion reactions in patients with sickle cell disease,” Stowell said. DHTRs are also the most fatal reactions in this patient group.

One of the biggest challenges with transfusing patients with SCD is that 20-50% of these individuals are already alloimmunized.

Why are DHTRs likely underestimated? One challenge is that these reactions are delayed. Occurring days to weeks after transfusion, the signs and symptoms may not trigger suspicion of a DHTR. In addition, DHTRs can also mimic vaso-occlusive crises, hindering the correct diagnosis. Lastly, allo-antibodies may not be detectable.

It may be time to revise the diagnosis of DHTRs. Current recommendations from the National Healthcare Safety Network (part of the Centers for Disease Control and Prevention) call for a positive direct antiglobulin test (DAT) between 24 hours and 28 days post-transfusion; and either a positive eluate or a newly identified allo-antibody; and either inadequate rise in post-transfusion Hb or unexplained spherocytes.

“This is very much focused on allo-antibody-positive DHTRs,” he said. A third of DHTRs can be allo-antibody negative.

A revised definition has been proposed in the “Society of Hematology 2020 guidelines for sickle cell disease: transfusion support.”² This definition includes:

1. A significant drop in hemoglobin within 21 days post-transfusion.
2. One or more of the following: a new red blood cell alloantibody; hemoglobinuria; accelerated fall in post-trxn HbA%; relative reticulocytopenia or reticulocytosis from baseline; significant LDH rise from baseline.
3. Exclusion of an alternate cause.

Another complication for preventing and diagnosing DHTR arises from information from one health system being available to other systems. A patient might receive a transfusion at hospital A, but that information is not available when the patient presents to hospital B. Collaborative groups, such as in Massachusetts, are working to improve adverse event reporting related to transfusions. The Massachusetts group has proposed revising the definition of DHTR; requiring an ICD10 code inclusion with AE reporting; repeated HbA measurements following episodic transfusion; and raising clinician and patient awareness.