Rh_null phenotype: molecular basis, serologic features, clinical manifestations, and transfusion challenges-a scoping...

The Rh_null phenotype is the rarest of the Rh blood group system phenotypes and is characterized by the complete absence of all Rh antigens on red blood cells (RBCs). This phenotype carries major clinical relevance because of chronic hemolysis and profound transfusion incompatibility. We performed a scoping review to summarize the molecular basis, serologic features, clinical manifestations, and transfusion challenges associated with published Rh_null cases. A systematic literature search of PubMed/MEDLINE and Scopus was conducted from database inception to May 2025. Eligible reports included case reports, case series, or observational publications of individuals with the Rh_null phenotype. Data were extracted and synthesized narratively according to a scoping review method. Six eligible publications describing eight individuals with the Rh_null phenotype were identified. Common findings included chronic hemolytic anemia, stomatocy tosis or spherocytosis, and reticulocy tosis. Despite generally moderate intrinsic hematologic manifestations, the Rh_null phenotype imposes a disproportionate transfusion burden because of near-complete donor scarcity. Anti-Rh29 alloimmunization was reported after transfusion or pregnancy exposure, restricting patients to Rh_null RBC units from family members, frozen RBC inventories, or rare donor registries. Early recognition, molecular characterization, and proactive integration of eligible individuals with the Rh_null phenotype into rare donor programs are critical for access to compatible blood.