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

Background: CD36, recently recognized as a distinct blood group system, encodes a class-B scavenger receptor involved in hemostasis and innate immunity. Anti-CD36 alloantibodies are an often-overlooked cause of platelet transfusion refractoriness (PTR), fetal–neonatal alloimmune thrombocytopenia (FNAIT), and bleeding disorders. Although newer assays are available, the relative effectiveness of platelet antibody tests remains uncertain. We review the clinical features of CD36 deficiency and alloimmunization, compare the Solid Phase Red Cell Adherence Assay (SPRCA) with ELISA for antibody detection, and propose a streamlined diagnostic algorithm for PTR. Materials and Methods: A retrospective cohort study was conducted at a tertiary center over 6.5 years, involving 2,333 patients who underwent platelet antibody testing. Antibody screening used parallel SPRCA and qualitative solid-phase ELISA, with confirmatory tests including MAIPA, molecular genotyping, and flow cytometry for CD36 antigen expression. Six illustrative cases with genetically or phenotypically confirmed CD36 deficiency were examined in detail. 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 = 0.451). ELISA identified additional antibodies in 18.4% of cases, whereas SPRCA alone detected 3.4%. Dual positivity strongly indicates pathogenic alloantibodies responsible for transfusion refractoriness. Conclusions: CD36 deficiency poses a significant immunohematologic challenge in PTR and FNAIT. Employing both ELISA and SPRCA for screening, along with reflex confirmatory testing, improves diagnostic accuracy for anti-CD36 alloimmunization, enhances transfusion strategies with CD36-negative platelet transfusions, and increases patient safety. Establishing rare donor registries is crucial for providing personalized transfusion support to affected individuals.