Clinical Impact of Delayed Hemolytic Transfusion Reactions in Sickle Cell Disease Cohorts

Blanka Nagy; K. Matuska; A. Gregor

doi:10.5281/zenodo.22818800

Authors

Blanka Nagy Department of Cellular Therapy and Transplantation, Vardar Center for Bleeding Disorders Research Author https://orcid.org/4976-9829-2982-8946
K. Matuska Department of Laboratory Hematology, Tundzha Institute of Transfusion Epidemiology Author https://orcid.org/4250-0431-6354-5936
A. Gregor Department of Hematology, Maas Institute of Myeloproliferative Disease Research Author https://orcid.org/6394-0222-0736-539X

DOI:

https://doi.org/10.5281/zenodo.22818800

Keywords:

sickle cell disease, delayed hemolytic transfusion reaction, hyperhemolysis syndrome, red cell alloimmunization, extended phenotype matching

Abstract

Graphical abstract

Background: Patients with sickle cell disease are alloimmunized against red cell antigens far more often than other transfused populations, underlying delayed hemolytic transfusion reactions (DHTR) that are frequently mistaken for ordinary vaso-occlusive crisis.

Objective: To synthesize the literature on DHTR epidemiology, presentation, hyperhemolysis, and the preventive and management strategies supported by cohort and case-series evidence.

Methods: Narrative synthesis of cohort studies, meta-analyses, and case series on alloimmunization, DHTR, hyperhemolysis, extended/genotype matching, and complement-directed management in sickle cell disease.

Findings: Alloimmunization prevalence has stayed near 29-30% across three decades; DHTR carries 6% mortality in adult cohorts and severe complications in a third of pediatric episodes; extended matching leaves roughly 9% still alloimmunized; and anti-C5 complement blockade produced favorable recovery in most patients with refractory hyperhemolysis in the largest reported series.

Conclusions: DHTR and hyperhemolysis are predictable consequences of persistent alloimmunization, and the largest near-term gains lie in earlier recognition, avoiding reflexive further transfusion, wider genotype-level matching, and expanded complement-directed rescue therapy.

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