Integrating HLA and HPA for Precision Transfusion: Anti-CD36–Mediated Refractoriness and Hemostatic Challenges

Abstract Background: CD36, recently designated as a distinct blood group system, is a multifunctional class-B scavenger receptor in hemostasis and immunity. Anti-CD36 alloimmunization remains an underrecognized cause of platelet transfusion refractoriness (PTR), fetal–neonatal alloimmune thrombocytopenia (FNAIT), and hemostatic complications. Despite the availability of advanced diagnostic assays, the clinical utility and concordance of different platelet antibody detection platforms remain poorly characterized.We aimed to delineate the clinical presentations of CD36 deficiency and alloimmunization, compare diagnostic performances of SPRCA and ELISA for antiplatelet antibody detection, and propose an optimized diagnostic algorithm for PTR management. Materials and Methods: A retrospective cohort of 2,333 patients undergoing platelet antibody workup was analyzed at a tertiary center over 5.5 years. Antibody screening employed parallel SPRCA and qualitative solid-phase ELISA, with confirmatory testing using MAIPA, molecular genotyping, and flow cytometry for CD36 antigen expression. Six illustrative cases with genetically or phenotypically confirmed CD36 deficiency were thoroughly evaluated. Results: ELISA detected antiplatelet antibodies in 33.6% of samples, while SPRCA detected them in 18.7%, with an overall concordance of 78.2% (κ = 0.45). ELISA identified additional antibodies in 18.4% of cases, whereas SPRCA alone identified 3.4%. Dual-positivity was highly predictive of pathogenic alloantibodies responsible for transfusion refractoriness. Conclusions: CD36 deficiency introduces a critical immunohematologic barrier in PTR and FNAIT. Parallel screening with ELISA and SPRCA, utilizing reflex confirmatory testing, enhances diagnostic precision for anti-CD36 alloimmunization, optimizes transfusion strategies using CD36-negative platelet transfusions, and improves patient safety. Establishing rare donor registries is essential for tailored transfusion support to affected individuals.