Integrating HLA and HPA in Precision Transfusion: Insights from Platelet Transfusion Refractoriness Driven by Anti-CD36 Alloimmunization and Multifactorial Hemostatic Complications

Purpose: CD36, recognized as a distinct blood group system, encodes a class-B scavenger receptor essential for hemostasis and innate immunity. Alloantibodies against CD36, although often overlooked, are a significant cause of platelet transfusion refractoriness (PTR), fetal–neonatal alloimmune thrombocytopenia, and immune-mediated bleeding. The comparative effectiveness of platelet antibody assays remains unclear. We aim to propose a streamlined diagnostic algorithm for PTR. Methods: This retrospective cohort study, conducted at a tertiary center, analyzed 2,453 patients undergoing parallel screening for platelet antibodies using both the Solid Phase Red Cell Adherence Assay (SPRCA) and qualitative ELISA over a period of nearly seven years. Confirmatory workflows included MAIPA, molecular genotyping, and flow cytometry for CD36 antigen expression. Six illustrative cases with genetically or phenotypically confirmed CD36 deficiency were comprehensively profiled. Results: ELISA detected antiplatelet antibodies in 33.5% of samples, while SPRCA identified them in 18.1%, yielding a moderate overall concordance of 78.1% (κ = 0.444). Among SPRCA-positive samples, 81.9% were confirmed by ELISA; for SPRCA-negatives, 22.8% were ELISA-positive, underscoring substantial assay discordance. Notably, 18.7% of cases were exclusively ELISA-positive, compared to only 3.3% detected solely by SPRCA. Dual assay positivity was highly specific for clinically significant platelet alloimmunization and PTR. Conclusion: Our findings highlight the critical role of combined ELISA and SPRCA screening, supplemented by confirmatory and molecular methods, in accurately identifying anti-CD36 alloimmunization. The study underscores the need for comprehensive diagnostic protocols, rare donor registry development and the broader implementation of CD36-negative platelet inventories to optimize personalized transfusion strategies and patient outcomes.