Immunology of Blood Transfusion Flashcards by Joel Glotfelty

Carry antigenic proteins and carbohydrates on their surfaces

Erythrocytes

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Each such molecule defines a

Blood Group

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The specific alleles in DNA, and the specific antigens present on rbc, define an individual=s

Blood Type

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Which blood groups are the most important in blood transfusion?

ABO and Rh groups

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Present in normal individuals, never exposed to foreign erythrocytes

Antibodies to ABO antigens

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However, formation of anti-Rh antibodies requires exposure to

Rh-antigen

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Formation of anti-Rh antibodies requires exposure to Rh antigen; preventing an immune response to them is important to prevent

Hemolytic Disease of the Newborn

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Terminal sugars on oligosaccharides of glycoproteins and glycolipids of the red cell membrane

ABO epitopes

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There are about one million copies of the epitope on each erythrocyte, and the oligosaccharide chains extend well away from the cell surface, so that an erythrocyte is a very good target for

Anti-ABO antibodies

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The precursor of ABO antigens is

H substance

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Genes of the ABO system encode enzymes which add terminal sugars to

H substance

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H substance with a terminal N-acetyl galactosamine added

A substance

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H substance with a terminal galactose added

B substance

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Converts H substance to A substance

The Ia enzyme

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Converts H substance to B substance

The Ib enzyme

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The product of the Io allele is non-functional and adds nothing to

H substance

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Individuals make antibodies to ABO antigens they

Do not possess

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These antibodies [isohemagglutinins or isoantibodies] are usually

IgM

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Their synthesis does not require exposure to foreign erythrocytes; they are made in response to similar polysaccharide structures in bacteria and plants. They are called

Natural Antibodies

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People of blood types A, B, AB, or O do not make

Anti-H

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People who cannot convert h to H do make

Anti-H antibodies

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On routine typing these people appear as Type O since they have neither A nor B antigens. This blood type is called

Bombay O

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The Bombay O type is rare in Caucasians but common in some

Asian populations

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Persons of Bombay O genotype will have transfusion reactions if they receive

Ordinary type O

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They can be identified because their serum anti-H antibodies agglutinate

Type O red cells

Defined by the antigens present on red cells

ABO blood type

ABO antigens are also present on endothelium and must be matched in

Organ transplant

Specifies a complex group of red-cell antigens

Rh system

By far the most important antigen is the

Rh0 or D antigen

Red cells of persons who are Rh+ have this antigen and red cells from people who are Rh- lack it

Rh0 or D antigen

Antibodies to Rh antigens are formed only as a result of exposure to

Rh incompatible blood

Anti-Rh antibodies are usually

IgG

Anti-Rh antibodies are usually IgG; they do not activate

Complement

Bind to rbc, opsonize them, and cause them to be phagocytosed and destroyed

Anti-Rh antibodies

They agglutinate red cells poorly and usually cannot be detected by direct agglutination

Anti-Rh antibodies

Rh incompatibility between mother and fetus can lead to

Fetal hemolytic disease

An Rh-negative mother carrying an Rh-positive fetus may be exposed to small numbers of fetal red cells, either as the result of small hemorrhages in the placenta during pregnancy, or, more commonly, when the placenta separates from the

Uterine Wall at Birth

She may then make

Anti-Rh+ antibodies

Maternal exposure to fetal rbc can be determined by use of an immuno-fluorescent assay for

Hemoglobin F

Can be detected by the Indirect Antiglobulin Test (IDAT)

Maternal anti-D antibodies

Maternal immune response to Rh antigen can be prevented by administration of

Anti-Rh+ immune globulin (Rhogam)

Often administered one or more times during pregnancy, without any testing if the mother is Rh- and the father Rh+

Rhogam

Maternal IgG antibodies to any red cell antigen can cause

Fetal Hemolytic Disease

Anti-ABO antibodies are normally IgM and do not cross the

Placenta

ABO antigens are present in soluble form in plasma and are present on many cell types; thus anti-ABO IgG antibodies may be neutralized before they can damage

Fetal RBCs

Maternal antibody to paternal platelet antigens can deplete fetal platelets and create a risk of

Fetal Hemmorhage

Detects antibodies bound to red cells in vivo which do not agglutinate them

The Direct Antiglobulin Test (DAT) (Direct Coombs test)

Tests for non-agglutinating antibodies are done under conditions that favor -Ex: low ionic strength medium and/or addition of polyethylene glycol (PEG)

Antibody binding

Detects free antibody to erythrocyte antigens

The Indirect Antiglobulin Test (IAT or IDAT) (Indirect Coomb's test)

Used in pre-transfusion testing to detect non-agglutinating antibodies in sera of blood donors and recipients

IDAT (indirect Coombs)

In the case of maternal-fetal Rh incompatibility, it is used to detect anti-Rh+ antibodies in maternal serum

IDAT (indirect Coombs)

In IDAT, to detect this antibody patient plasma is first mixed with erythrocytes bearing the antigen of interest; then, in a second step, we add

Anti-IgG antibody

What are the two pre-transfusion tests for non-agglutinating antibodies to erythrocytes?

DAT and IDAT

Determines the ABO and Rh antigens present on donor and recipient erythrocytes, and the antibodies to these antigens that are present in plasma

Typing

ABO and Rh antigens are determined by agglutination of red cells with antisera for

A, B, and Rho(D). (A and B are sometimes referred to as isoantigens.)

The ABO type is confirmed by mixing patient serum with know Type A and B cells to detect

Anti-A and anti-B antibodies

Test results for antigens and antibodies should be consistent with each other: If erythrocytes react with anti-A but not anti-B, the 1. ) Blood type should be? 2. ) Serum should contain?

1. ) A | 2. ) Anti-B but not anti-A antibodies

Detects anti-rbc antibodies to the many minor blood groups

Screening

Allelic variation exists for many erythrocyte membrane components besides ABO and Rh. Antibodies to these are uncommon and usually

Non-agglutinating

Serum of donors and recipients is screened by mixing it with members of a panel of type O red cells carrying known

Minor blood group antigens

Antibodies to these antigens are detected by hemolysis or agglutination; antibodies incapable of hemolysis or agglutination are detected by the

IDAT

Ensures that the actual unit of blood transfused is compatible with the patient

Cross-matching

Blood is cross-matched by mixing donor cells with recipient plasma [the major cross-match]. If agglutination is not observed, non-agglutinating antibody is sought by the

IDAT

May result in hemolysis, fever, chills, and low back pain, and may progress to shock, presence of free hemoglobin in blood and urine, and renal failure

Immediate transfusion reactions

In a transfusion reaction, there may be decreased hematocrit or increased

Bilirubin

If whole blood, rather than washed erythrocytes, is transfused, there may be reactions to

WBC or plasma proteins

Delayed transfusion reactions (3-10 days after transfusion) are more common than

Immediate reactions

The usual source of immediate reactions is

Human error

Delayed reactions result from a immune response to

Minor antigens

Antibodies to HIV do not appear until

1-2 months after infection

Because of the recent epidemic, is now screened for by PCR or similar tests

West Nile Virus

If the recipient is immunocompromised, blood is also screened for

Cytomegalovirus [CMV]

Serologic screening is impractical, screening relies on a history taken at the time of donation

Plasmodium [the cause of malaria] and Babesia

There is no immune response to

Bovine spongiform encephalopathy (mad cow disease)