ABO and Rh Blood Group Systems

first person to perform forward and reverse blood typing; founder of ABO blood group (blood types A,B,O. AB was discovered later)

Landsteiner

ABO group contains 4 major blood types

A

B

O

AB

it's believed that the immunizing source for naturally occurring antibodies anti-a and anti-b is an exposure to

environmental bacteria similar to A and B antigens

almost all healthy people over the age of _____ have naturally occurring ABO antibodies to the antigens they lack

3-6 months

Landsteiner demonstrated that a person's serum had _________ against an ____________ absent from his own RBCs. AKA

antibodies

antigen

isohemagglutins

in blood, ABO antigens are found in substantial amounts on

RBCs

platelets

Landsteiner's rule states that

if ABO antigen is present on cells, corresponding antibody will be present in serum

if ABO antibody is present in serum, corresponding antigen will be absent on cells

the most serious transfusion reactions are due to incompatibility involving the _______ blood group system

ABO

only blood group system that automatically makes antibodies to the antigen that the individual lacks

ABO

incompatible ABO transfusion results in

acute intravascular hemolysis

renal failure

death

ABO reagents from human serum aren't normally used due to

non-specificity

mixtures from unwanted antibodies in serum

ABO typing reagents are manufactured from ___________ derived from ________

monoclonal antibodies

culture cell lines (animals)

major advantage of monoclonal antibodies

reproducibility

anti-a reagent is

blue

anti-b reagent is

yellow

anti-a1 and anti-h are usually, and usually not used in ABO testing, but used to

colorless

resolve ABO discrepancies

there is always a _________ relationship between the forward and reverse type; one serves as a check on the other

inverse reciprocal

testing for an Indvidual's ABO antigens (unkown antigen) on their RBCs using ANTISERA (known ABO antibodies)

forward grouping (front typing)

testing for the presence or absence of individual's ABO antibodies (unknown antibodies) using reagent red blood cells (known antigens)

reverse grouping (back typing)

predominant ABO phenotype among all four population categories

O

least prevalent ABO phenotype amongst all four population categories

AB

major antigens of ABO system

A

B

H (O)

major antibodies of ABO system

anti-A (IgM)

anti-B (IgM)

anti-A,B (IgG)

anti-H (IgM or IgG)

ABO titers are too low for detection until _______ of age, so blood type results obtained prior to are considered

3-6 mos

invalid

antibody production peaks at _________ of age and declines later in life

5-10 years

elderly people have _____ levels of anti-A and anti-B, therefore antibodies may be ________ in _______ grouping

lower

undetectable

reverse

the ABO antibodies are predominantly _______

IgM

ABO antibodies are produced without any exposure to RBCs AKA

naturally occuring

anti- A,B cannot be ________ when adsorbed with A or B cells

separated into a pure specificity

in group O serum, _____ is the major isotype for anti-A and anti-B

IgG

ABO antibodies can cause _______________ if wrong ABO group is transfused

rapid intravascular hemolysis

ABO genes locus

chromosome 9

Gene O is considered amorph because

no detectable antigen is produced in response to its inheritance

A and B are referred to as ___________, whereas AA, BB, OO are _______

phenotypes

genotypes

formation of ABH antigens results from interaction of the genes at three separate loci

ABO

Hh

Se

ABO, Hh, and Se genes don't code for the production of antigens but rather produce _________ that __________

specific glycosyltransferases

add sugar to a basic precursor substance

basic precursor substance to which the sugar is added to form ABH antigens AKA

paragloboside

glycan

ABH antigens on RBC are constructed on

oligosaccharide chains of a Type 2 precursor substance

_________ precursors are found in body fluids and secretions like plasma, milk, urine, and tears

type 1

H gene locus

chromosome 19

H gene has ____ major alleles

2

H, h

H gene produces an enzyme, ___________, that transfers ________ to terminal ____________ of the type 2 precursor chains to form ___ antigen

α-2-L-fucosyltransferase

L-fucose (sugar)

galactose

H (O)

H gene produced no detectable gene product, so type 2 precursor chains remain

unchanged

_________ people carry either single or double dose of H gene and produce ________

almost all

H transferase (α-2-L-fucosyltransferase)

amount of H antigen on red cells based on agglutination with anti-H is represented as

O>A2>B>A2B>A1>A1B (most H to least H)

production of N-acetylgalactosaminyltransferase leads to transfer of N-acetyl-D-Galactosamine (GalNAc) to end of type 2 precursor, resulting in

Group A antigen (A gene)

production of D-galactosyltransferase leads to transfer of D-galactose (GAL) to end of type 2 precursor chain, resulting in

Group B antigen (B gene)

A and B genes are located on

chromosome 9

type O individuals RBCs react strongly with

Ulex europaeus (anti-H lectin)

the o gene is referred to as an amorph because

no enzyme or product is expressed when its present

the presence of ABO soluble substances in body secretions is based on the ABO genes inherited and another set of genes called _______ (secretory genes) which regulate their formation

Sese

______% of the population are secretors

80

precursor substance of secretors that is modified to form H substance

type 1

most common A subgroup; converts almost all of the H precursor structure into its antigens; has the strongest reaction at cold temperatures (4C) but also CLINICALLY SIGNIFICANT when reacts at 37C

A1

approximately ______% of all group A or (AB) individuals are A1 (or A1B)

80

second most common A subgroup; 22-35% of this subgroup will form Anti-A1 antibodies (the only subgroup to form naturally occurring antibodies)

A2

A subgroup that exhibits classic MIXED-FIELD AGGLUTINATION reaction (small agglutinates in a sea of non-agglutinated free RBCs); represents 1:1,000 group A/AB people

A3

A subgroup that's intermediate between A1 and A2

A int

Lectin used to differentiate between A1 and A2 phenotypes (anti-A1 lectin)

dolichus biflorus

seed extracts that agglutinate human cells with some degree of specificity

lectins

this reagent agglutinates A1 cells, but not A2

dolichus biflorus

individuals that do not inherit the H gene from either parent have the _________ phenotype (homozygous h/h inheritance)

Bombay

individuals with Bombay phenotype cannot make the __________ needed to convert type 2 precursor chains into type 2 H chains. therefore, their type 2 chain does not add _______

H transferase

fucose

Bombay blood type as ____, even if they inherit A or B genes because they cannot transfer A or B sugars onto the RBCs

O

Bombay phenotype produces _________ which reacts with all O cells, therefore they can only receive blood from _________

anti-H

other Bombay individuals

anti-H lectin

ulex europaeus

the RBCs of Bombay phenotype do not react with _________

ulex europaeus (anti-H lectin)

diseases and effects on expression of H,A, B antigens/antibodies

weaker reactions

pseudoantigens acquired (affecting forward grouping)

leukemia

chromosome 9 translocation

hemolytic disease

hodgkin's disease (mixed field agglutination)

acquired B phenomenon (GI tract)

acquired B phenomenon results from

GI issues:

intestinal obstruction

carcinoma of colon/rectum

disorders of lower intestinal tract

carcinoma of stomach/pancreas

increased permeability of intestinal mucosa (entry of E. coli O86 to px blood)

ABO discrepancy implies that

forward and reverse ABO grouping do not agree

mistyping a patient/donor can lead to transfusion with ABO incompatible blood, resulting in

in-vivo RBC destruction; death

most ABO discrepancies are ________ in nature, and can be resolved by

technical

checking work and repeating test

technical sources of typing errors

cell suspension too light/heavy

clerical errors

sample mix-up

missed agglutination/hemolysis

failure to add reagents

not following manuf. instructions

non-calibrated centrifuge

contaminated reagents

warming during centrifugation

if discrepancy persists after technical review, gather

patient's age

diagnosis

transfusion history

medications

Ig levels

pregnancy history

when discrepancy encountered, results must be ___________ but interpretation of type must be

recorded

delayed until discrepancy is resolved

discrepancy group due to missing or weakly reacting ANTIBODIES

group I

discrepancy group related to weakly reacting or missing ANTIGENS; LEAST frequently encountered

group II

discrepancy group due to plasma or PROTEIN abnormalities

group III

miscellaneous discrepancies

group IV

presence of two cell populations in a single individual (twins, transfusions, bone marrow transplant, exchange transfusions, fetal-maternal bleeding); seen in group I discrepancies

chimerism

resolution of group I discrepancies

incubate RT for 15-30 minutes

if necessary, incubate at 4C spin and read again

O cell control and check cell

resolution of group II discrepancies

incubate RT for 15-30 minutes

if necessary, incubate at 4C spin and read again

O cell control and check cell

**excess amounts of BGSS will neutralize reagent anti-sera, leaving no unbound antibody to react with patient cells (wash 3 more times to avoid BGSS)

discrepancies that result in rouleaux formation (pseudoagglutination)

group III

resolution of group III discrepancies

wash patient cells several additional times with saline to remove proteins causing rouleaux

SALINE replacement technique

some examples of group IV discrepancies include

polyagglutination (T-antigen)

cold reactive antibodies (allo- & auto-)

warm autoantibodies

unexpected ABO isoagglutinins

antibodies against anti-sera

resolution of group IV discrepancies

lectins if T-activation suspected

auto-antibody auto-absorbed out

elutions

Rh specific antigens reside on _________ versus the __________ antigens ABO and Hh

proteins

carbohydrate

Rh antigens are very ___________; they are produced after exposure to foreign RBCs

immunogenic

Rh blood system is composed of ___________ different RBC antigens

over 50

_____% of Rh positive

85

Anti-D was first found in the serum of a mother who had delivered a stillborn infant and required a transfusion. Her husband (same blood type) was selected as a donor, but she exhibited symptoms of an

acute hemolytic transfusion reaction

Anti-D discovered in 1930s by

Levine and Stetson

Rh system identified in 1940s by

Landsteiner and Wiener

the human anti-Rh identified by ___________ and the animal anti-Rh identified by _______ were not the same

Levine and Stetson

Landsteiner and Wiener

most complex of the human blood group systems

Rh

_____ major antigens make up Rh system; what are they

5

D

C

E

c

e

theory of Rh genetic control that proposed the Rh locus contains 3 distinct genes

Fisher-Race theory

theory of Rh genetic control that proposed the Rh locus contains ONE GENE responsible for producing an agglutinogen containing a series of blood factors; Rh gene produced at least 3 FACTORS within an agglutinogen

Wiener theory

the 'd' notation in FIsher-Race theory is only used to

denote the absence of 'D' antigen

predominant Rh gene combination in black haplotype

Dce