blood group

Blood Groups

I. INTRODUCTION

II. BLOOD GROUP SYSTEMS

III. LANDSTEINER’S LAW

IV. CLASSICAL ABO BLOOD GROUPING SYSTEM

V. RHESUS BLOOD GROUPING SYSTEM

VI. CLINICAL IMPLICATION OF BLOOD GROUPING

VII. BLOOD TRANSFUSION

INDEX

Austrian Karl Landsteiner(1900) discovered -•Human blood possess different antigenic and immune properties•Blood clumping was an immunological reaction.

Nobel Prize in Physiology and Medicine in 1930.

Introduction

CLASSIFICATION-

Major blood group system

Minor blood group system

Familial blood group system-

Kell, Duffy, Lutheran, Lewis, Deigo, kidd Etc.

Blood Group System

LANDSTEINER’s LAW-

1.If an agglutinogen is present on red blood cell membrane ,the corresponding agglutinin must be absent in the plasma.

2.If an agglutinogen is absent on red blood cell membrane, then corresponding agglutinin must be present in the plasma.

I. Discovery

II. Antigen and Antibodies

III. Inheritance

ABO Blood Group System

• Karl Landsteiner(1900) classified human blood into A,B,O groups.

• Von Decastello and Sturli (1902) discovered AB blood group.

• Von Dungern and Hirszfeld(1911) divided group A into 2 subgroups A1 and A2.

Discovery

Appear in the sixth week of fetal life.

Present on red cell membrane and in other tissues like salivary glands, pancreas, kidney EXCEPT CNS also in body fluids.

H antigen is also present usually in all individuals.

Antigens

• Basic precursors for ABH antigens.• Type-1 chain beta (1-3) linkage• Type-2 chain beta (1-4) linkage

Biochemistry

Glucose

Galactose

NacetylglucosamineGalactose

Precursor Substance (stays the

same)

Formation of H Antigen

• Glucose • Galactose • N-acetylglucosamine

• Galactose

• H antigen

• RBC

• Fucose

L Fucosyl Transferase Enzyme (product of H gene)

Glucose

Galactose

N-acetylglucosamineGalactose

RBC

Fucose N-acetylgalactosamine

N-acetylgalactosaminyl Transferase (product of A gene)

Formation of the A antigen

Formation of the B antigen

• Glucose

• Galactose • N-acetylglucosamine

• Galactose

• RBC

• Fucose

• Galactose

D-galactosyl Transferase(product of B gene)

O GENE

• Group O Group A

Fewer H

antigen sites

A

A A

AA

Many H antigen sites

Why do Group O individuals have more H antigen than the other groups?

The O gene is a silent allele. It does not alter the structure of the H substance….that means more H antigen sites.

• Mostly IgM type.• Produced by bone marrow and lymph gland cells .• Known as cold antibodies.

Anti-A and Anti-B agglutinins

Titre of antibodies

Why antibodies produced in people who do not have the respective antigens in their red blood cells?

Immune system form antibodies against the antigens recognised as non-self(i.e. not present in the own body).

Alpha -agglutinins- alpha-1 and alpha -proper.20% 40

%8%

32%

Group A has 2 subgroups -A1 and A2.Group AB -A1B and A2B.

Types of ABO Blood Group

Inheritance of ABO blood groupFollows Mendelian Law.In 1924, Felix Bernstein proposed presently accepted theory.

Heterozygous: AO or BOHomozygous: AA or BB

Mom Dad Offspring Blood Group

AA BB 100% AB

BO OO 50% each of B or O

OO OO 100% O

OO AO 50% each of A or O

Examples-

Genotype And Phenotype

BLOOD GROUP

ANTIGEN ANTIBODY

GENES at 9q34.1

GENES at 19 q13.2

A A Anti-B AA,AO HH

B B Anti-A BB,BO HH

AB AB None AB HH

O Neither(H) Anti-A and anti-B

OO HH

Bombay phenotype

No ABH Antigen

Anti-A ,Anti-B, Anti -H

any hh

The Rhesus Blood Group System

I. Discovery of Rh systemII. Antigen and antibodiesIII. Inheritance IV. Haemolytic disease of newborn

History of the Rh System Levine and Stetson(1939) described a hemolytic transfusion reaction in an obstetric patient following delivery of stillborn infant.

An antibody was isolated from the mother’s serum. It was postulated that the fetus and the

father possessed a common factor that the mother lacked.

While the mother carry the fetus, the mother was exposed to this factor and developed antibody against the transfused red cells from the father and resulted in transfusion reaction.

At that time ,the responsible antibody was not named.

Landsteiner and Wiener(1940) injected RBC’s of rhesus monkeys in rabbits- developed antibodies.

The antibody was named as anti-Rh.

When resulting antiserum was mixed with human RBC’s, then agglutination occurred.

The RBC antigen responsible for this reaction was called as Rh factor.

The antibody discovered by Levin and Stetson in the mother was subsequently re-examined and found identical in activity as the anti-Rh antibody found by Landsteiner and Weiner.

So this work led to discovery of Rh system.

Anti-rhesus formed by the animals was renamed anti-LW (Landsteiner and Wiener).

Fisher and Race(1943 and 1944) discovered C, E, c, e Ag and their corresponding antibodies anti-C , anti -E ,anti- c ,anti -e.

Rh Antigens

• Rh system involves 6 Rh antigens D,d,C,c,E,e

Rh positivePresence of rh D85% occurrence

Rh negativeAbsence of rhD

15% Occurrence

Integral membrane proteins with an active phoshpholipid component.Present on red blood cells.D antigen is commonest and most immunogenic.

• IgG type.• Known as warm antibodies.• Produced by exposure to foreign Rh antigen .

Rh Antibodies

• D Ag is inherited as a dominant gene D.

• Genotype of individual may be:

DD

Dd

dd

Inheritance

Examples-

Heterozygous Rh +

Homozygous Rh-

50% hetrozygous rh+50% homozygous rh-

• ABO Incompatibility- immediate reaction as antibodies are naturally present.

• Rh Incompatibility- First exposure-

Primary response

Immunological memory

Second exposure-

Immediate and severe response.

Incompatibility

Agglutination

No complications But Rh antibody is

produced

To Rh negative personFrom Rh positive person

Rh antigen reacts with Rh antibody

First transfusion

Second transfusion

Haemolytic Disease Of Newborn

I.Erythroblastosis fetalis-• Erythroblastosis

Mechanism- Rapid production of red blood cells by haematopoeitic tissues of baby in order to replace haemolysed RBC’s.

• Anaemia

II.Icterus gravis neonatorum

III.Kernicterus

IV.Hydrops fetalis

Manifestations

HYDROPS FETALIS

ERYTHROBLASTOSIS FETALIS

ICTERUS GRAVIS NEONATORUM

KERNICTERUS

I. Anti-D Prophylaxis –• Based on principle antibody mediated immunosuppression. • Inject anti-D antibody in mother soon after child birth.• Fetal Rh typing, then give anti- D antibody to expectant mother between 28 to 30 weeks.

II. Exchange transfusion

Prevention And Treatment

• THE Ii SYSTEM- Weiner et al (1956)

2 antigens –I and i

Difference-• At birth , RBC’s are rich in i Ag ,not I Ag.• In first second years of life, gradual changeover from i to I.

Other Blood Group Systems

• THE DUFFY SYSTEM

Cutbush , Mollison and Parkin(1950).

System has 3 blood groups-Fya ,Fyb and Fyab.

Fyab blood groups are resistant to plasmodium vivax whereas Fya and Fyb are susceptible to vivax malaria.

Cont…

• KELL SYSTEM- Coombs ,Mourant , Race(1946).

Antigen - K

Rare In India(.3 To .7%)

• P BLOOD GROUP SYSTEM- Landsteiner and Levine in(1927).

2 blood groups- P positive

P negative

Cont…

• MN SYSTEM- Landsteiner and Levine(1927).

Required for-• Paternity tests• Anthropological and genetic studies.

Cont…

• LEWIS SYSTEM-

Mourant and Andresen(1946,1948)

2 antigens- Lea and Leb.

Ceppelline(1955) showed, Lea substance in saliva was controlled by dominant gene Le

and its allele le.

Not real antigens because they are present in plasma and saliva, RBCs acquire by

adsorption from plasma.

Cont…

I. In blood transfusion.

II. In preventing HDN due to Rh Incompatibility.

III. In paternity disputes.

IV. In medicolegal cases.

V. In knowing susceptibility to diseases.

Clinical Implications

I. Indications

II. Donor and Recepeints

III. Precautions

IV. Hazards

Blood Transfusion

I. Blood loss.

II. For quick restoration of Hb.

III. Exchange transfusion.

IV. Blood diseases like- aplastic anaemia, leukaemia,hemophilia,purpurae,clotting defects.

V. Acute poisoning.

VI. Acute infections or fever when gamma globulin is needed.

VII. Shock

Indications

• Donor selection-I. Healthy and age between 18 to 60 years.

II. Haemoglobin > 12 gm%

III. Weight more than 45 kg.

IV. Females should not be Pregnant, lactating and menstruating.

V. No diseases like AIDS, Viral Hepatitis ,Malaria, Syphilis.

VI. No past H/O jaundice , HTN,TB, and cardiac diseases.

Donor And Recepient

Blood transfusion-who can receive blood from whom?

Blood Group

Antigens Antibodies Can give blood to

Can receive

blood from

AB A and B None AB AB, A, B, O

A A B A and AB A and O

B B A B and AB B and O

O None A and B AB, A, B, O O

• For safe and compatible blood transfusion-

• ABO and Rh typing• Cross matching• Antibody screening

Investigations

Determination Of Blood Group

Blood Typing

Under Microscope

Human RBC before (left) and after (right) adding serum containing antibodies.

II. Cross Matching- Major cross matching -Donor’s RBCs are mixed with recepient’s plasma.

Minor cross matching- Recepients RBC’s are mixed with donor’s plasma.

When no agglutination then only donors blood can be transfused.

Cross Matching

III. Antibody Screening –

Antibody Screening

IV. Rh positive blood should never be transfused to Rh negative blood.

V. Check blood bag for correct label.

VI. Transfuse blood at slow rate(not >20 drops/min) under proper aseptic measures.

VII. Careful watch on recepient’s condition.

VIII. Stop transfusion if reaction occurs.

• Hemoglobinemia• Haemoglobinuria• Chestpain and chills• Fever• Shock• Renal failure• Death

Haemolytic

• Cardiorespiratory symptoms• Acute left ventricular failure• Immunological reaction• Pulmonary edema• Allergic reactions.• Transmission of diseases.• Thrombophlebitis,air embolism.

Non- Haemolytic

Transfusion reactions