The Rh blood group system, especially the D antigen, is crucial in transfusion medicine and obstetrics. Weak D phenotypes, caused by mutations in the Rhesus D antigen (RhD) blood group (RHD) gene, result in reduced antigen expression, posing challenges in serological testing and clinical management. Variability in detection methods leads to inconsistent results, making accurate classification difficult. Molecular techniques like polymerase chain reaction and DNA sequencing have significantly improved the identification of weak D variants, offering more reliable transfusion strategies and reducing the risk of alloimmunization. However, challenges such as lack of standardized protocols, cost constraints, and population-specific variations remain. In obstetrics, proper management of pregnant women with weak D is essential to prevent hemolytic disease of the fetus and newborn. Non-invasive prenatal testing using cell-free fetal DNA shows promise in predicting RhD incompatibility and minimizing unnecessary Rh immune globulin administration. Future advancements in high-throughput genotyping and discovery of novel RHD alleles could enhance RhD testing accuracy and efficiency. Standardizing RHD genotyping and adopting genotype-based management strategies for Rh immune globulin therapy and red blood cell transfusions will improve patient safety and clinical outcomes. This review examines the molecular basis, challenges, and future prospects in weak D phenotype management.

• Weak D phenotype
• Rhesus antigen
• RhD blood group genotyping
• Allele
• Transfusion
• Allo-immunization
• Pre-natal
• Non-invasive prenatal testing
• Rhesus immunoglobulin

• alloimmunization
• antibody screening
• blood transfusion
• leukoreduced blood
• red blood cell
• thalassemia major