Sainath PB, Ramaiyan V. Weak D phenotype in transfusion medicine and obstetrics: Challenges and opportunities. World J Exp Med 2025; 15(2): 102345 [DOI: 10.5493/wjem.v15.i2.102345]
Corresponding Author of This Article
Velmurugan Ramaiyan, PhD, Professor, Department of Pharmacy, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, NH 48, Chennai 602105, Tamil Nādu, India. ramaiyan.dr@gmail.com
Research Domain of This Article
Hematology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Exp Med. Jun 20, 2025; 15(2): 102345 Published online Jun 20, 2025. doi: 10.5493/wjem.v15.i2.102345
Weak D phenotype in transfusion medicine and obstetrics: Challenges and opportunities
Prasanna Bharathi Sainath, Velmurugan Ramaiyan
Prasanna Bharathi Sainath, Department of Pharmacology, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, Chennai 602105, Tamil Nādu, India
Velmurugan Ramaiyan, Department of Pharmacy, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, Chennai 602105, Tamil Nādu, India
Author contributions: Sainath PB designed the overall concept and outline of the manuscript; Ramaiyan V contributed to the discussion and design of the manuscript; Sainath PB and Velmurugan R contributed to the writing, and editing of the manuscript, illustrations, and review of the literature; and all authors thoroughly reviewed and endorsed the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Velmurugan Ramaiyan, PhD, Professor, Department of Pharmacy, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, NH 48, Chennai 602105, Tamil Nādu, India. ramaiyan.dr@gmail.com
Received: October 16, 2024 Revised: March 4, 2025 Accepted: April 3, 2025 Published online: June 20, 2025 Processing time: 182 Days and 21.4 Hours
Abstract
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.
Core Tip: In this review, we explore the weak D phenotype, caused by Rhesus D antigen (RhD) blood group allele variations, which reduces RhD expression on red blood cells, impacting transfusion strategies and anti-D immunization risks. Molecular and novel genotyping techniques may be necessary for exact identification, and mitigate the risk of alloimmunization in these weak D traits. Implementation challenges such as standardization and financial constraints are quite prevalent in several countries. Hence it emphasizes the importance of accurate weak D phenotype identification and the potential of inculcating molecular techniques in transfusion medicine and obstetrics.
