4 - THE RHESUS (Rh) BLOOD GROUP SYSTEM

Rh blood group system

this blood group system is comprised of some 40 different antigens

D, C, c, E, e

5 Rh blood group system of particular importance

1. Fisher-Race

2. Wiener

3. Rosenfield

3 nomenclatures involved in the Rh system

Fisher-Race terminology

assumes that 3 closely linked genes are inherited from each parent

Fisher-Race terminology

The most common alleles that occupy these loci are described as: D and, C and c, E and e

d allele

Each gene with the exception of d codes for a specific antigen that can be detected on the red cell membrane. It is possible that this allele is a silent allele

Weiner nomenclature

assumes the inheritance of a single gene from each parent

Weiner nomenclature

Each gene is a mosaic structure comprising a variable number of blood factors

R1 gene

Weiner nomenclature:

This gene codes for factors that correspond to Dce

R2 gene

Weiner nomenclature:

This gene codes for factors that correspond to DcE

Ro gene

Weiner nomenclature:

This gene codes for factors that correspond to Dce

Rz gene

Weiner nomenclature:

This gene codes for factors that correspond to DCE

Rosenfield system

D = Rh : 1

C = Rh : 2

E = Rh : 3

c = Rh : 4

e = Rh : 5

Fisher-Race

D (called big D)

C

E

c

e

Wiener

Rho

rh’

rh’’

hr’

hr’’

Rosenfield

Rh : 1

Rh : 2

Rh : 3

Rh : 4

Rh : 5

Fisher-Race terminology

Traditionally, it is used to describe Rh antigens

Weiner terminology

Traditionally, it is used when describing an Rh phenotype

Fisher-Race

Rh positive

Dce

DcE

Dce

DCE

Weiner

Rh positive

R1

R2

Ro

Rz

• 40%

• 16%

• 2%

• 0.08%

Identify the Gene frequency:

Fisher-Race ; Weiner

Rh positive

• Dce ; R1 →

• DcE ; R2 →

• Dce ; Ro →

• DCE ; Rz →

• Rho, rh’, hr’’

• Rho, hr’, rh’’

• Rho, hr’, hr’’

• Rho, rh’, rh’’

Identify the Agglutinogens:

Fisher-Race ; Weiner

Rh positive

• Dce ; R1 →

• DcE ; R2 →

• Dce ; Ro →

• DCE ; Rz →

Fisher-Race

Rh negative

dce

dCe

dcE

dCE

Weiner

Rh negative

r

r’

r’’

ry

• 38

• 1

• 1

• Very rare

Identify the Gene frequency:

Fisher-Race ; Weiner

Rh negative

• dce ; r →

• dCe ; r’ →

• dcE ; r’’ →

• dCE ; ry →

• hr’ hr’’

• rh’ hr’’

• hr’ rrh’’

• rh’ rh’’

Identify the Agglutinogens:

Fisher-Race ; Weiner

Rh negative

• dce ; r →

• dCe ; r’ →

• dcE ; r’’ →

• dCE ; ry →

Levine and Stetson

2 scientists who discovered the D antigen in 1939

Cc Ee antigens

By the mid-1940, what were the 4 antigens discovered?

D antigen

The most immunogenic of all Rh antigens

Rh positive individuals

They express the D antigen on RBC

They constitute 85% of the population

Rh negative individuals

They do not express the D antigen on RBC (i.e., dCe/Dce)

They constitute 15% of the population

anti-D

Approximately 70% of Rh negative individuals produce _______ if given Rh positive blood

Because C and E antigens are not as immunogenic as D

Why is routine typing of C and E antigens not performed?

Du

a weak form of D antigen rarely found among Caucasians but common in Blacks (22%)

Du red cells

give weak or negative reactions with Anti-D

Du

It is detected by performing an indirect antiglobulin test (Du test)

1. Acquired Du

2. Hereditary Du

3. Du variant

3 categories of Du

Acquired Du

the inheritance of C in the transposition to D (dCe/DcE results in the weakened expression of the D antigen on red cell); these individuals do not produce anti-D if exposed to Rh positive blood

Hereditary Du

the reason for the weakened expression of the D antigen in these individuals is not known

Du variant

the D antigen normally consists of at least 4 parts, if one or more parts is missing then the antigen is weakly expressed

1. High grade Du

2. Low grade Du

2 grades of Du variant

High grade Du

This is not passed on to future generations since development depends upon the rare r' (Cde or CdE) chromosomal arrangement

High grade Du

It reacts with either complete or incomplete anti-Rh D and only rarely requires the use of antiglobulin test for its detection

Low grade Du

It is direct product of inherited gene and can be passed on to future generation

Low grade Du

It is usually detected by the antiglobulin test after first sensitizing the cells with anti-D sera

positive

negative

Du individuals should be considered as a Rho (D) ________ blood DONOR and transfused with Rh (D) _________ blood as RECIPIENT

Rh negative

It is a belief that patients do not have to be typed, and that the safest, most efficient and the easiest way to handle the issue is to routinely transfuse __________ blood to all patients who are negative when tested with anti-sera

Du

common among Negroes

Rh antibodies

are natural antibodies

Rh antibodies

classified as immune antibodies because they are present only after exposure to Rh antigens through ingestion, injection or pregnancy

Rh antibodies

do not ordinarily react in saline medium since they are mostly of the IgG class

1. First order Rh antibodies

2. Second order Rh antibodies

3. Third order Rh antibodies

3 varieties of Rh antibodies

First order Rh antibodies

react strongly with specific Rho antigens in saline medium and react less strongly in a proteir medium

First order Rh antibodies

saline agglutinins, bivalent antibodies, complete antibodies

Second order Rh antibodies

albumin-reacting, incomplete, monovalent antibodies

Second order Rh antibodies

react visibly with specific antigen in protein medium; in saline medium, they weakly combine with the antigen but do not produce a visible reaction

Third order Rh antibodies

typical Rh antibodies, antiglobulin Rh antibodies

Third order Rh antibodies

react visibly with specific antigens in an antiglobulin medium only

Rh typing

It is performed with the commercial anti-D antibodies which are produced from the serum of Rh negative persons who have been immunized to the Rho (D) factor

Slide test

What is this method for Rh typing?

• A rapid method employing very potent anti-D (Rho) antiserum

• The cell-antiserum mixture is heated on an illuminated Rh view box with a temperature of about 45°C

• Agglutination if positive should be visible within 2 minutes to avoid drying and rouleaux formation

Tube test

What is this method for Rh typing?

• The cell-anti-serum mixture is incubated at 37°C for half hour

• Agglutination should be achieved if positive after the incubation period; agglutination can be made stronger through centrifugation at 1,500 rpm for 1 minute or at 3,000 rpm for 15 seconds

Test for Du variant

Whenever there is no agglutination in Rh typing, what test should follow?

Rh-positive

Du positive

Rh typing:

Where there is agglutination, the person is __________, when there is no agglutination, the person is either Rh negative or ____________

Rh antigen

Unlike the ABO system, the ___________ are found only in the RBC surface

Detection of Du

• in order to determine whether the patient's cells are Rho(D)-negative or possibly Du positive, the patient's cells are incubated with anti-Rho(D) typing serum to coat the cells

• after incubation, the cells are centrifuged and examined for agglutination; if no agglutination is observed, the cells are further tested for the antiglobulin test by adding anti-human globulin (Coomb's reagent)

Detection of Du

• Agglutination indicates the patient is Du positive and is classified as Rh (D) positive patient

• No agglutination indicates the patient is Rh(D) negative and Du negative

MEDICO-LEGAL USE OF BLOOD GROUPS

Using the common blood group system (ABO, Rh, MNSs) it is possible to exonerate approximately 50% of wrongly accused males from being the father of the infant in question

Blood typing

It can never prove paternity and only either disprove it or result in equivocation