Weak D phenotype in transfusion medicine and obstetrics: Challenges and opportunities

Table 1 Clinical Interpretation of widespread weak D in distinct groups

Number	Ethnic group	Weak D subtypes	Clinical interpretation	Ref.
1	Caucasian	Weak D types 1, 2, 3	Can be treated as D-positive for RhIG administration and transfusion	[32,34]
2	Asian	Asia type DEL (RHD 1227 G > A)	Appears D-negative in conventional serology but can be treated as D-positive	[34]
3	Iranian	Weak D type 15	Most prevalent; weak D types 1, 2, and 3 account for 15% of cases	[33]
4	Brazilian	Weak D types 1, 2, 3, 4	Most frequent in descending order; presence of both caucasian and arican D variants	[35]
5	Australian	Weak D types 1, 2, 3	Found in 75% of weak D samples; some other types (1.1, 5, 15, 17, 90) showed partial D-epitope profiles	[36]
6	Chinese	Various	45 RHD alleles were identified, including 11 novel variants; 3.5% carried DEL alleles	[37]

RHD: Rhesus D antigen blood group.

Table 2 Summary of the challenges and opportunities in managing weak D phenotypes and the importance of Rhesus D antigen blood group genotyping and standardized practices for improved patient care and resource management

Number	Aspect	Challenge	Opportunities	Ref.
1	Serological testing	Variable results and interpretations across laboratories. Discrepancies between automated gel and manual tube testing	Standardization of testing methods and interpretation guidelines. Use of multiple testing methods to improve accuracy	[32,50]
2	RhD interpretations	Inconsistent reporting terms are used to interpret weak D-reactive maternal RhD types. Risk of misclassification of partial D as weak D	Development of consistent immunohematologic terminology. Integration of RHD genotyping for accurate classification	[32,49,50]
3	RhIG management	Unwarranted antiglobulin testing leads to recommendations against giving RhIG in some cases. Unnecessary RhIG administration for certain weak D types	RHD genotype-guided management of RhIG therapy. Early pregnancy RHD genotyping to optimize RhIG use	[11,32,48]
4	Fetomaternal hemorrhage testing	Use of contraindicated fetal rosette test for weak D-reactive newborns, risking false-negative results	Implementation of appropriate testing methods for accurate assessment of fetomaternal hemorrhage	[32]
5	RBC transfusion	Unnecessary use of D-negative RBCs for patients with certain weak D types	Conservation of D-negative RBC units through RHD genotyping and appropriate management of weak D types 1, 2, and 3 as D-positive	[11,48]
6	Population differences	Variation in RHD allele distribution among different populations	Population-specific genotyping strategies and transfusion policies	[47,56]
7	Novel alleles	Continuous discovery of new RHD alleles	Ongoing research to characterize new alleles and their clinical significance	[51,52]
8	Timing of genotyping	Delayed genotyping leads to complicated clinical management	Early RHD genotyping, preferably during early pregnancy, to guide patient management	[48,53]

RhD: Rhesus D antigen; RhIG: Rh immune globulin; RHD: Rhesus D antigen blood group; RBCs: Red blood cells.