Researchers suggested that delayed hemolytic transfusion reaction (DHTR) is a relatively common and challenging complication to diagnose and treat sickle cell disease (SCD), as published in the American Journal of Case Reports.

Patients with SCD typically receive transfusion therapy for the expected severe anemia episodes inherent in the condition. Although this treatment is safe and used in various clinical situations other than SCD, it is not exempt from complications. For example, it includes transfusion reactions as presented in this case series.

DHTR commonly sources on a prior immunological event, which sensitizes the patient prompting alloantibodies formation. Later on, these alloantibodies to red blood cell antigens will trigger DHTR with subsequent blood transfusions in which patients with SCD customarily receive. 

In this study, the authors reported 2 cases of DHTR in which both patients showed evidence of alloimmunization from prior blood transfusions, according to the DHTR definition of the American Society of Hematology. 

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The authors discussed the resemblance between DHTR and vaso-occlusive crisis presentation, which may harbor some explanations why DHTR remains underdiagnosed. Nonetheless, DHTR is still the most common adverse event reported after transfusions in patients with SCD, with a prevalence varying between 30% and 50% and an indeterminate incidence ranging greatly from 0.001% to even 13.52%.

“DHTR is considered one of the most deleterious complications of transfusion in SCD patients. The diagnosis and management of DHTR is very challenging, especially because it can present differently in this population. A high index of clinical suspicion is needed in addition to the laboratory criteria,” the authors said.

Besides the point that DHTR is underdiagnosed, it may also be mistreated. To this day, there are no formal treatment protocols for DHTR in patients with SCD. “There are no validated treatment protocols for DHTR and no consensus on the standard dosage for the suggested treatments due to the lack of well-designed randomized-controlled trials,” the authors explained.

The need for more clinical consideration of DHTR is highly desirable in patients presenting with transfusions reactions, especially as DHTR can display different symptoms in every patient, making diagnosis more demanding.

Furthermore, additional clinical trials must take place in the future to analyze and define DHTR treatment with optimal doses, taking into account all that it includes as patient improvement, costs, and adverse effects of such drugs. 


Alwaheed AJ, Alqatari SG, AlSulaiman AS, AlSulaiman RS. Delayed hemolytic transfusion reaction in sickle cell disease: a case series. Am J Med Case Rep. Published online January 5, 2022. doi:10.12659/ajcr.934681