Rh BLOOD GROUP

SYSTEM
Rh Blood group System
Second in importance next to the ABO blood group
in the field of transfusion medicine
One of the main causes of Hemolytic Disease of the
Newborn (HDN)
Rh antigens are highly immunogenic
Rh status is routinely determined in blood donors,
transfusion recipients, and in mothers-to-be
Rh Blood group System
RHD and RHCE genes, located in chromosome 1,
encode the Rh antigens
Rh proteins are closely associated with Rh-
associated antigen (RhAG)
RhD Protein: D antigen
RhCE Protein: C/c and E/e antigens
Rh Blood group System
Rh Blood group System

The majority of Rh antibodies are of the IgG type

Rh antibodies rarely activate complement; they bind

to RBCs and mark them up for destruction in the
spleen (extravascular hemolysis)
Rh Phenotypes
Rh haplotype DCe: most common in Caucasians
(42%), Native Americans (44%), and Asians (70%)

Rh haplotype Dce: most common in Blacks (44%)

Rh D-negative phenotype: most common in

Caucasians (15%), less common in Blacks (8%), and
rare in Asians (1%)
Rh Phenotypes
In Caucasians, the Rh D-negative phenotype results
from a deletion of the RHD gene
In Africans, there are three molecular backgrounds
that give rise to the Rh D-phenotype:
RHD gene deletion
RHD pseudogene
RHD hybrid gene that contains nucleotide
sequences from the RHCE gene, produces no D
antigen and abnormal C antigen
Uncommon Rh Phenotypes
Weak D
An Rh phenotype caused by a single amino acid
switch in the transmembrane region of the RhD
protein
This disrupts how the RhD protein is inserted into
the RBC membrane, reducing the level of expression
of RhD
Adequate levels of D antigen are present and
because there has been no change in D epitopes,
the formation of anti-D is prevented
Uncommon Rh Phenotypes
C in Trans to RHD
Position effect
The allele carrying RHD is trans (or in the opposite
haplotype) to the allele carrying C; for example,
Dce/dCe
The Rh antigen on the RBC is normal, but the steric
arrangement of the C antigen in relationship to the D
antigen appears to interfere with the expression of D
antigen
Uncommon Rh Phenotypes
Partial D
This phenotype is usually caused by the creation of a
hybrid RhD and RhCE protein
The hybrid protein is similar enough to RhD to be
correctly inserted in the RBC membrane, but it lacks
several epitopes found on the complete RhD protein
If a person with the partial D phenotype encounters
the complete D antigen on transfused RBCs, they
may form anti-D and suffer from a transfusion
reaction
Uncommon Rh Phenotypes
Del
A phenotype occurring in individuals with mutant
RHD gene that alters expression of RhD protein
Red blood cells possess an extremely low number of
D antigen sites that most reagent anti-D are unable
to detect
Adsorbing and eluting anti-D from the individuals
red cells is often the only way to detect the D antigen
Uncommon Rh Phenotypes
Rh Null Syndrome
Failure to express any Rh antigens on the RBC
surface
Amorphic: Due to mutation in each of the RHCE
genes inherited from each parent and the common
deletion of the RHD gene; normal RHAG gene
Regulator: Due to mutation in the RHAG gene. This
results in no RhAG protein expression and
subsequently no RhD or RhCE protein expression on
the RBCs
Uncommon Rh Phenotypes
Rh Null Syndrome
The absence of the Rh complex alters the RBC
shape, increases its osmotic fragility, and shortens
its lifespan, resulting in a hemolytic anemia that is
usually mild in nature
Patients are at risk of adverse transfusion reactions
because they may produce antibodies against
several of the Rh antigens
Studies
Strategy for managing maternal variant RHD alleles in
Rhesus D negative obstetric populations during fetal
RHD genotyping
Fetal RHD screening programs that aim to reduce
unnecessary antenatal anti-D prophylaxis are being
introduced into clinical practice.
Fetal RHD status was defined by testing cell-free
fetal DNA in maternal plasma.
Studies
Hyland, Catherine A; Gardener, Glenn J; O'Brien,
Helen; Millard, Glenda; Gibbons, Kristen; et
al. Prenatal Diagnosis; Charlottesville 4.1 (Jan 2014): 56-62
3
Studies
RH Blood Groups and Diabetic Disorders: Is There an
Effect on Glycosylated Hemoglobin Level?
Investigated the possible relationship between the
RH system and HbA1c in Diabetes
Glucose and HbA1c levels are increased in DCcEe
subjects and decreased in ddccee subjects as
compared to the mean values of other genotypes.
Studies
Bottini, et al. Human Biology; Apr 2000; 72,2;
ProQuest Central. Pg. 287
Sources
Flegel, W. The genetics of the Rhesus blood
group system Blood Transfus. 2014 Apr; 5(2): 5057.
NCBI. The Rh blood group. Retrieved from
https://www.ncbi.nlm.nih.gov/books/NBK2269/
Marion, S. Epitopes on Rh proteins. Cong Intl Soc
Blood Transfus. 2000 Jul; 78(1): 116-120.