Heme Exam 1 - Engle Transfusion 1

Front 1

Antigen

Back 1

Antigen:

A substance of a significant molecular weight that is able to trigger an immune response.
May be proteins, polysaccharides, or chemicals.

Front 2

Antibody

Back 2

Antibody

Serum proteins that are produced in response to stimulation by a foreign antigen and is capable of reacting specifically with the antigen that caused its production.

Front 3

Alloantibody

Back 3

Alloantibody

Antibody directed against antigens from individuals of the same species

Front 4

Autoantibody:

Back 4

Autoantibody:

Antibody directed against self

Front 5

Primary Immune Response
Primary antibody involved:

Back 5

Primary Immune Response

Encountered the antigen for the 1st time
Primary antibody involved: IgM

It has a inductive period 3-7 days from 1st detected and starts to make detectable amount of antibodies for it. start to generate IgM and it will switch isotypes to IgG later in time.

Front 6

Secondary Immune Response
Primary antibody involved:

Back 6

Secondary Immune Response


Reencountered the antigen
Primary antibody involved: IgG
Memory cells from the primary immune response are activated and produce a stronger and a more rapid response.

Here there is no inductive period, memory cells are faster, stronger respond, generating IgM and mainly IgG.

Front 7

Immunoglobulin structure.

Back 7

2 light chain: kappa and lambda
2 heavy chain: IgM-mu, IgG-gamma, IgA-delta, IgE

Front 8

IgG Antibodies***

Back 8

IgG Antibodies

-80% of the total serum Ig
-Major Ig in secondary response
-Most clinically significant in transfusion medicine
-Important in HDN and in transfusion of PRBC
-Can “fix” complement-not as good as IgM
-Will cross the placenta

Front 9

IgM Antibodies**

Back 9

IgM antibodies

-Major Ig in primary response
-Highest theoretical valence (10)
-Can’t cross the placenta
under normal conditions

Front 10

Hemolytic Disease of the Newborn

Back 10

Hemolytic Disease of the Newborn

HDN is the destruction of the RBCs of the fetus and/or neonate by maternal antibodies.

If fetal cells enter the mother’s circulation, the mother’s immune may recognize them as foreign and produce an antibody.

This IgG class antibody can cross the placenta and attack the baby’s RBCs during the course of gestation.


Tx: RhoGam

Front 11

Types of HDN

Back 11

1. ABO HDN
Can be seen in any pregnancy, including the 1st
Less severe than Rh HDN
Classically seen in Group O mother’s who give birth to Group A babies in which an IgG anti-A,B attacks the baby’s A antigens.

2. Rh HDN
Typically not seen in the 1st pregnancy

More severe than ABO HDN

In 95% of the cases, the maternal antibody is directed at the D antigen in the Rh family.

RhoGam is administer to try to prevent this type of HDN from occurring.

3. Other Types of HDN:
Anti-S, anti-s, anti-Kell, etc.
Typically not seen in the 1st pregnancy

Front 12

RhIg (RhoGam) purpose

Back 12

RhIg (RhoGam) purpose

To prevent active immunization to the D antigen by the use of a high-titered RhIg anti-D injection.

Front 13

RhIg (RhoGam) purpose
Mechanism of Action

Back 13

The RhIg anti-D attaches to the fetal Rh positive RBCs in the maternal circulation.
The fetal antibody-coated RBCs are removed by the mother’s spleen.
The RBC antigens are thus unavailable for the dendritic cells to present antigen to the T helper cells.
In other words, RhIg helps to remove D positive fetal cells from the maternal circulation before the immune system has a chance to make the anti-D antibody.

Front 14

Indications For RhIg

Back 14

Indications For RhIg

1. Antenatal
Given at 28 weeks of gestation to all Rh negative mothers who lack the anti-D antibody

2. Postpartum
Given within 72 hours after delivery of a Rh positive infant.
If for any reason this injection is missed and not given at 72 hours, it should be given as soon as possible.


Abortion (spontaneous and induced)
Because the type of the baby is unknown

Others:
Ectopic pregnancy

Abdominal trauma

Greater than 40 weeks of gestation

Front 15

List major Major Blood Groups

Back 15

List major Major Blood Groups?

ABO System
Rh System
MNSs
Kell System
Duffy System
Kidd System
Lutheran System
Xga System

Front 16

The ABO System
Blood Group Percentages?

Back 16

The ABO System
Blood Group Percentages?

The most important of all blood group systems.

Blood Group Percentages:
Group O: 45%
Group A: 40%
Group B: 11%
Group AB: 4%



The only blood group system in which individuals, without an exposure to transfusion or pregnancy, predictably have antibodies in their serum to which they lack the antigens.

Front 17

Inheritance of the ABO Blood Group

Back 17

A person inherits one ABO gene from each parent.

The ABO genes are codominant, which means that the patient will express both ABO genes.

Front 18

Formation of A, B, and H RBC Antigens

Back 18

Formation of A, B, and H RBC Antigens?


The ABO genes don’t code for the A antigen or B antigen directly.

They code for specific glycosyltransferases that add sugars to a basic precursor substance.
The precursor substance on RBCs is referred to as type 2 precursor substance.

Front 19

If the patient has inherited the A gene, what produces the sugar? what sugar?

Back 19

If the patient has inherited the A gene, what produces the sugar? what sugar?


ά-3-N-acetylgalactosaminyltransferase produces the sugar, N-acetyl-D-galactosamine (A antigen), which is transferred to the H substance.

Typically, each RBC contains as many as 810,000 to 1,170,000 A antigens.

Front 20

If the patient has inherited the B gene, what produces the sugar? what sugar?

Back 20

If the patient has inherited the B gene, what produces the sugar? what sugar?


ά-3—D galactosyltransferase codes for the D-galactose sugar (B antigen), which is transferred to the H substance.

Typically, each RBC contains 610,000 to 830,000 B antigens.

Front 21

AB patient has more what blood group?

Back 21

AB patient has more what blood group?

More B.
Both A and B genes are inherited.

Note:
The B enzyme seems to compete more efficiently for the H substances that the A antigen.
A Antigen Sites/RBC: 600,000
B Antigen Sites/RBC: 720,000

Front 22

O patient has more what blood group?

Back 22

O patient has more what blood group?

If the patient has NOT inherited either the A or B genes, he lacks both glycosyltransferases.

Neither the A or B antigens are expressed on their H substances on their RBCs

Front 23

The genotype “hh” is extremely rare and is seen only in _?

Back 23

The genotype “hh” is extremely rare and is seen only in _?

“Bombay patients”.

Front 24

Bombay Phenotypes (Oh) result in what? what about cells and serum?

Back 24

Bombay Phenotypes (Oh) result in what?what about cells and serum?

Result:
No H substance formed
ABO genes can’t be expressed
ABH antigens can’t be formed on the RBC

Cells:
No A or B antigens present

Serum:
Anti-A is present
Anti-B is present
A very dangerous Anti-H is present

Front 25

Transfusing a Bombay Patient

Back 25

Transfusing a Bombay Patient

The Bombay anti-H is potent and strongly reacts at 37°C!!!

It is an IgM complement binding antibody that will cause RBC lysis.

Transfusing normal O blood will cause immediate cell lysis and a potentially fetal transfusion reaction.

Bottom Line:
Only Bombay blood can be safely transfused to a Bombay patient.

Front 26

The Rh Blood Group System

Back 26

The Rh Blood Group System

Rh refers to a complex blood group system that is currently composed of over 50 different antigenic specificities.

Of these, five (D, C, E, c, e) constitute 99% of the clinical work in the Rh field.

After the ABO group antigens, the D antigen is considered the most clinically significant RBC antigen for X-match purposes.

Front 27

Fisher-Race: The DCE Terminology

Back 27

Genetics:
Each person inherits a set of Rh genes from each parent.
One D or d=Lack of D, one C or c=lack of C, and one E or e=lack of E.

The combination of maternal and paternal haplotypes determines one’s genotype and dictates one’s phenoytpe.

Front 28

Rh Antibodies
Causes of Rh Antibody Production?

Back 28

Rh Antibodies
Causes of Rh Antibody Production?


Most Rh antibodies are IgG.
Causes of Rh Antibody Production:
Pregnancy
Transfusion

The antigens of the Rh system are very good at provoking an immune response.
D is the most immunogenic of all of the Rh antigens!!
Fact: Exposure to <0.1 ml of Rh positive RBCs can stimulate the production of an anti-D antibody in an Rh negative patient.
Rhogam (RhIg)

Front 29

What is the is the most immunogenic of all of the Rh antigens?

Back 29

What is the is the most immunogenic of all of the Rh antigens?

D

Fact: Exposure to <0.1 ml of Rh positive RBCs can stimulate the production of an anti-D antibody in an Rh negative patient.
Rhogam (RhIg)

Front 30

The MNSs System
Anti- M and Anti-N antibodies?
Anti-S and anti-s antibodies?

Back 30

The MNSs System
Anti- M and Anti-N antibodies?
Anti-S and anti-s antibodies?

“Mixed System”

Anti- M and Anti-N antibodies:
Typically “cold” IgM antibodies
Most are clinically insignificant

Anti-S and anti-s antibodies:
Typically “warm” IgG antibodies
RBC stimulated via pregnancy or previous transfusion ***
Will bind complement and cause severe hemolytic transfusion reactions with hemoglobinuria or HDN

Front 31

What is the Kell System and the 2 major antigens?

Back 31

What is the Kell System and the 2 major antigens?

First discovered in the serum of Mrs. Kellaher
An antibody reacted with the RBCs of her newborn infant, her older daughter, her husband, and about 7% of the population.

Two Major Antigens:
1. The K (Kell) antigen
2. k (Cellano) is the other major antigen in this system.

Front 32

Anti-K antibody vs Anti-k (cellano) antibody?

Back 32

Anti-K antibody vs Anti-k (cellano) antibody?

Anti-K:
Has been known to cause severe hemolytic transfusion reactions and severe HDN.

Commonly seen antibody in blood bank

No Difficulty in Finding Compatible RBCs:
Only 9% of the population is K+
91% of the population is K-


Anti-k (cellano) antibody:
Has been known to cause severe hemolytic transfusion reactions and severe HDN.


Rarely seen antibody in blood bank.


Difficulty in Finding Compatible PRBCs:
99.8% of the population is k+
0.2 % of the population is k-
Bottom Line: Only 2 PRBC units in 1,000 will be compatible!

Front 33

The Duffy Blood Group System,
Two Major Antigens are?

Back 33

The Duffy Blood Group System,
Two Major Antigens are?

Named after Mr. Duffy, a multiply transfused hemophiliac who in 1950 was found to have the first described example of anti-Fya.

Two Major Antigens:
Fya and Fyb

Anti-Fya and Anti-Fyb Antibodies
Anti-Fya is more common than anti-Fyb
Both are typically IgG
Both have been associated with acute and delayed hemolytic transfusion reactions

Front 34

The Duffy-Malaria Association
Two Major Antigens are?

Back 34

The Duffy-Malaria Association

Since 1955, it has been known that Africans and black Americans were resistant to infection by Plasmodium vivax and that these populations are Fy(a-b-).
The Fy(a-b-) phenotype is prevalent in blacks but virtually nonexistent in whites.

It has been suggested that Fya and Fyb are the invasion receptor for P. vivax.

Front 35

The Kidd Blood Group System
Two Major Antigens are?

Back 35

The Kidd Blood Group System

DANGEROUS, below detectable limits!!!!

Name in honor of Mrs. Kidd, whose infant had HDN.

Special Blood Bank Significance:
Difficult to detect
Common cause of hemolytic transfusion reactions

Two Major Antigens:
Jka and Jkb

Anti-Jka and Anti-Jkb: Dangerous antibodies!!
1. Often shows weak reactions because the titer of anti-Jka or anti-Jkb quickly declines in-vivo:
-The antibody screen may appear as negative!
2. Often found in combination with other antibodies

Front 36

The Lutheran Blood Group System
2 major antigens?

Back 36

The Lutheran Blood Group System

Discovered in 1945 in the serum of Mrs. Luteran, a patient diagnosed with lupus erythematosus.

Her name was misspelled and the antibody was named Lutheran instead of Luteran.

Two Major Antigens: Lua and Lub

Front 37

The Lutheran (005) Blood Group System

Back 37

The Lutheran (005) Blood Group System

Blood bankers seldom deal with antibodies to the Lutheran system because their antigens are either very high or very low-incidence.
Lua: 8% of the population
Lub: 99.8% of the population

Front 38

The Lutheran Antibodies
Anti-Lua vs Anti-Lub

Back 38

The Lutheran Antibodies
Anti-Lua vs Anti-Lub?

Anti-Lua
Most example are IgM and therefore are usually clinically insignificant.

Unusual Fact:
IgA anti-Lua antibodies have been observed.


Anti-Lub
Almost the entire population is Lub antigen positive

Finding compatible Lub antigen negative PRBCs is next to impossible****
Least incompatible transfusion

Front 39

The XG Blood Group System and the atigen associated with it?

Back 39

The XG Blood Group System and the atigen associated with it?


Unique in the blood group systems in that inheritance is on a sex linked basis.
89% of the female population is positive
66% of the male population is positive

Contains only a single antigen, Xga.

Anti-Xga has not been attributed to causing transfusion reactions or HDN.

Front 40

Compatibility Testing

Back 40

Compatibility Testing

1. ABO & Rh testing

2. Antibody Screen
Antibody identification if the screen is positive

3. Crossmatch
Testing of the patient’s serum or plasma with the donor’s RBCs in-vitro

Front 41

Type & Screen Vs
Type & Cross
-component
-purpose
-important note

Back 41

Type & Screen Vs
Type & Cross

Type & Screen:
Components:
ABO, Rh type & Antibody Screen

Purpose:
This ensures that if the patient does have an antibody, the blood bank has adequate time to provide antigen negative blood.

Important Fact:
If the patient’s antibody screen is negative, 99.9% of all ABO compatible PRBCs will be compatible.


Type & Cross
Components:
ABO, Rh, antibody screen, and crossmatch
Crossmatch: In vitro mix of patient’s blood with the donor’s blood

Purpose:
To provide a reasonable confidence that transfused RBCs have a acceptable survival rate and there should not be significant destruction of the recipient’s own RBCs.

Important Note:
This should be ordered when there is an intent to transfuse (i.e. type & cross for 2 units)

Front 42

Transfusions Important Facts:

Back 42

Transfusions Important Facts:

1. Pretransfusion compatibility testing cannot guarantee normal survival of transfused RBCs in the recipient’s circulation.

2. The potential benefits of RBC transfusion should always be weighed against the potential risks.
Delayed hemolytic transfusion reactions
Analphylatic transfusion reaction
HIV or Hepatitis C positive PRBCs

Front 43

Rates of Risks in transfusion

Back 43

Rates of Risks in transfusion

Honhemolytic febrile transfusion reaction
Most common type
1-2%

Allergic
1%

Immediate hemolytic and delayed hemolytic transfusion reactions:
1:6,000

Fetal immediate
1:100,000

HIV Infection
1:2,135,000