Blood Groups

Dosage is most commonly seen with what blood groups?

Kidd, Duffy, Rh, MNS

Neutralization of ABO

Saliva (secretor)

Neutralization of Lewis

Saliva (secretor for Leb)

Neutralization for P1

Hydatid cyst fluid, Pigeon egg fluid

Neutralization for Sda

Urine

Neutralization for Chido, Rogers

Serum

Warm-reactive antibodies:

React best at 37 C or IAT IgG Require exposure Cause HDN/HTRs Significant

Cold-reactive antibodies:

React best below 37 C IgM Naturally occurring (no txn or pregnancy required for formation) No HDN/HTRs* Insignificant* *Exception = ABO

Enzyme-enhanced antigens:

ABO family:

• ABO blood group

• Lewis blood group

• I/i blood group

• P blood group Rh blood group Kidd blood group

Enzyme-decreased antigens:

MNS blood group Duffy blood group Lutheran

Enzyme unaffected antigens:

Kell blood group

Secretor gene is on which chromosome?

Chromosome 19

What is a secretor?

A person able to make A or B antigens in their secretions (saliva)

Type I chains are what and where are they found?

GlycoPROTEINS In: secretions and plasma

Type II chains are what and where are they found?

GlycoSPHINGOLIPIDS On: RBC

What does Se gene do?

Adds fucose to type I chains at terminal galactose --> type I H

What does H gene do?

Adds fucose to type II chains at terminal galactose --> type II H

How many people have Se gene?

80%

H gene is on which chromosome?

Chromosome 19

How many people have H gene?

almost 100% (except Bombay)

Group A sugar

N-acetylgalactosamine

Group B sugar

Galactose

Relative amounts of H by blood group

O>A2>B>A2B>A1>A1B

ABO ag genes are on which chromosome?

Chromosome 9

What makes ABO antibodies different from the typical warm vs cold-reactive antibodies?

They are clinically significant and naturally occurring Cold-reactive, IgM

Which ABO blood group is most common?

O

Group O: Genotype, Antigen, Antibody, Unique features

Genotype = OO (O gene is non-functions, no sugars added) Antigen = H Antibodies = anti-A (IgM and IgG), anti-B (IgM and IgG), anti-A,B (anti-A,B = IgG, which crosses placenta and is most common form of HDN) Bombay and Para-Bombay

Most common form of HDN

ABO (anti-A,B = IgG which crosses placenta unlike IgM ABO ab)

Ulex europaeus lectin

Agglutinates H ag

Which lectin agglutinates H ag?

Ulex europaeus

Dolichos biflorus lectin

Agglutinates A1 and Sda ag

Which lectin agglutinates A1 ag?

Dolichos biflorus

Which lectin agglutinates Sda ag?

Dolichos biflorus

Vicea graminea lectin

Agglutinates N ag

Which lectin agglutinates N ag?

Vicea graminea

Group A: Genotype, Antigen, Antibody, Unique features

Genotype = AA, AO Antigens = A,H Antibodies = anti-B (primarily IgM) Subgroups and Acquired B

BS1 lectin

Agglutinates B ag

Which lectin agglutinates B ag?

BS1 lectin

Group A subgroups

A1 = 80% (more A ag in A1) A2 = 20% (less A ag in A2) (1-2% A2 and 25% A2B have anti-A1 = insignificant, but a pain when you find it and have to work it up) Can use lectin, Dolichos biflorus (which agglutinates A1 only), to differentiate the two

Group B: Genotype, Antigen, Antibody, Unique featrues

Genotype = BB, BO Antigens = B,H Antibodies = Anti-A (primarily IgM) B subgroups exist but are not relevant Acquired B and B(A)

Group AB: Genotype, Antigen, Antibody, Unique featrues

Genotype = AB Antigens = A,B (very little H) (can be A1,B or A2,B) Antibodies = none Acquired B, B(A)

Which ABO blood group is the least common?

AB

ABO Discrepancy

Disagreement between the interpretations of the forward and reverse grouping

When do we not do forward and reverse typing for ABO blood type?

Newborns <4 mo or when recomfirming testing done elsewhere (in which case you do cell typing only)

Reasons for ABO discrepancies: antigen problems

Lack of expected antigens:

• A or B subgroups

• Transfusion or transplant Unexpected antigens:

• Acquired B phenotype

• Recent marrow/stem cell transplant

• Polyagglutinable RBCs/Nonspecific agglutination

Reasons for ABO discrepancies: antibody problems

Lack of expected antibodies:

• Immunodeficiency

• Abnormally HIGH concentrations of Ab (prozone phenomenon)

• Neonates, elderly, immunocompromised

• Transplantation or transfusion Unexpected antibodies:

• Cold auto/alloantibodies

• Anti-A1

• Rouleaux (false positive)

• Tranfusion or transplantation

Acquired B phenotype:

• Seen in:

• Forward and reverse reactions:

• Mechanism:

• How to sort out:

• Seen in: colon cancer, intestinal obstruction, g- sepsis

• Forward and reverse reactions: Forward = AB (weak B), Reverse = A

• Mechanism: bacteria deacetylate group A --> galactosamine which reacts with reagent (only) anti-B (not patient's anti-B)

• How to sort out: acidify serum (re-acetylates galactosamine), acetic anhydride (same), autoincubation (won't react with patient's anti-B), BS-1 lectin (agglutinate only true group B cells, not acquired B cells)

Bombay phenotype:

• Antibodies:

• Forward and reverse reactions:

• Problem:

Can't make H antigen (hh phenotype)

• Antibodies: anti-H, anti-A, anti-B

• Forward and reverse reactions: Forward = O, Reverse = O, but antibody screen wildly positive and all units incompatible

• Problem: requires blood from other Bombay

Para-Bombay phenotype:

• Antibodies:

• Forward and reverse reactions:

Have Se gene but not H gene --> (Ah, Bh, ABh phenotype)

• Antibodies: anti-H in serum

• Forward and reverse reactions: Forward = bombay/O, Reverse = H, A or B ag (unless group O)

B(A) Phenotype:

• Problem:

Patient really is group B, but with forward test like AB (weak reaction with anti-A)

• Problem: cross-reaction with a form of anti-A, testing using different anti-A shows real type (B)

Most frequent result of ABO incompatibility:

HDN (usually mild)

Most frequent blood bank fatality:

Severe acute HTR

Most common cause of severe acute HTR due to ABO incompatibility:

Clerical errors

Lewis blood group:

• Which chain?

• Gene:

• Secretor:

• Non-secretor:

• Antigens:

• Antibodies:

• Consequences of incompatibility:

• Unique features:

• Which chain? type I

• Gene: Le

• Secretor: Le (a-b+)

• Non-secretor: Le (a+b-)

• Antigens: Lea, Leb (Leb is more frequent)

• Antibodies: naturally occurring, IgM, mostly in Le (a-b-), cold-reacting, neutralize with saliva

• Consequences of incompatibility: rare HTR (more commonly anti-Lea), no HDN

• Unique features: Le ag decrease in pregnancy, Children's Lewis type may varry, H.pylori may att ach via Leb ag, Le (a-,b-) in children increases risk of UTI

What percent of blacks are Le (a-b-)?

22%

What percent of whites are Le (a-b-)?

6%

What makes Lewis unique?

Lewis antigens decrease in pregnancy --> can develop transient, insignificant Lewis antibodies in pregnancy Le(a-b+) peple don't make anti-Lea (b/c have Lea just not on RBC) Children's Lewis blood type may vary/progress H.pylori may attach via Leb ag Le (a-,b-) in children increases risk of UTI

Rule of Bs:

Any blood group with a and b = b is always more common than a (except Kidd where a=b or a is slightly more comon than b)

I/i blood group:

• Expression:

• Related to what other blood group?

• Antibodies:

• Unique features:

• Expression: age dependent (Big I in big people, little i in little people)

• Related to what other blood group? built on chains related to ABO

• Antibodies: cold-reacting, IgM, naturally occurring, almost always autoantibodies because almost everyone has I/i

• Unique features: Auto-anti I = cold agglutinin disease, Mycoplasma pneumonia; Auto-anti i = infectious mononucleosis, usually not a problem

Unique features/Classic associations with I/i:

• Auto-anti I:

• Auto-anti i:

• Auto-anti I: cold agglutinin disease, Mycoplasma pneumoniae

• Auto-anti i: Infectious mononucleosis, less problematic than auto-anti-I

What are the 3 P antigens and which is the most common?

P1, P, Pk Psubscript1 is most common (positive P1 and P, negative Pk)

What does the P antigen do?

Parvovirus B19 receptor

What happens and how common is it to lack all three P ag?

Very rare! Make anti-P1PPk --> IgG --> causes HTR, HDN and early abortions

Name three unique features/classic associations with P blood group:

1. P ag is parvovirus B19 receptor

2. Pk ag is a receptor for various bacteria and toxins

3. Paroxysmal cold hemoglobinuria (biphasic IgG with anti-P specificity --> binds at cold temp, hemolyzes at warm temp = Donath-Landsteiner biphasic hemolysin; was a/w syphilis and now a/w viral infections in kids)

4. P1 ab titers increase in hydatid cyst fluid (Echinococcus) and bird handlers (bird feces has P1-like substance)

P1 antibody characteristics and unique features:

Cold-reacting, naturally occurring, insignificant, IgM Titers increase in hydatid cyst disease (Echinococcus) and bird handlers (bird feces has P1-like substance)

Second most important blood group after ABO

Rh

Know the Fisher-Race/Wiener Rh blood group nomenclature

R1: DCe r': dCe R2: DcE r'': dcE R0: Dce r: dce Rz: DCE ry: dCE

Frequency of The Big Four haplotypes:

Whites: R1>r>R2>R0 Blacks: R0>r>R1>R2 Asians: R1>R2>r&R0

Which blood group has the most severe and prototypical HDN?

Rh

Rh antibodies:

Warm-reacting IgG Exposure required Significant (unexposed --> 80% will make anti-D with one unit D-pos RBC; exposed --> HTR with extravascular hemolysis; HDN)

What is Weak D phenotype?

D+ individual who requires IAT to detect D ag -->

• weak D test all D neg blood donors

• don't have to weak D test all D neg recipients (although often done, esp. in pregnant women)

Reasons for Weak D:

C in trans Weak form of R0 Partial/Mosaic D

What is Rh null?

No Rh antigens

What is associated with Rh null?

Hemolytic anemia with stomatocytes Altered activity of S, c and U antigens Rh mod = similar but less severe (still with hemolysis)

Associations with Rh:

WAHA

What are the compound Rh antigens?

G = ag present with either C or D f = ag present when c and e are on the same chromosome (r and R0)

Kidd antigens:

Jka, Jkb (Jka slightly more common)

Kidd antibodies:

IgG, but good at fixing complement Warm-reacting Exposure required

Unique things about Kidd:

Dosage Variable antibody expression (ab often disappears with time/storage) Delayed HTR (Intravascular, often severe) Mild HDN (Child is only one ag different from mom - dosage)

Glycophorin A carries what?

Carries M and N ag

What carries M and N ag?

Glycophorin A

Glycophorin B carries what?

Carries S, s, and U ag

What carries S, s and U ag?

Glycophorin B

Frequency of MNSs ag

M=N s>S S-s- (2% AA) may also be U- if black (<1% AA)

MNSs ab

M and N ab are mostly opposite S,s and U Anti-M and Anti-N: naturally occurring, cold-reacting, IgM, dosage, insignificant (anti-M has been a/w HDN uncommonly) Anti-S, Anti-s and Anti-U: requires exposure, warm-reacting, IgG, minimal dosage, significant

Enzyme effects on MNSs ags

Enzymes destroy M, N and S, but do not really effect s

What is 'N' and why does it matter?

Terminal aa seqence on glycophorin B, that matches glycophorin A
Not really N, but close enough to prevent most M+N- people from making anti-N
Present in all, except those who lack glycophorin B (S-,s-,U-) --> most who make clinically significnat anti-N are african-americans (

How can anti-N be induced?

Hemodialysis --> formaldehyde sterilization of the machine --> modification of N ag

Duffy ag and relative frequency:

Fyb>Fya (Fya is more common in Asians than caucasians)

What is the most common Duffy phenotype in blacks?

Fya-b- (68%)

Which Duffy ag is more common in Asians than in caucasians?

Fya

Duffy ab: which is more common and what are the characteristics?

Anti-Fya is more common and significant than anti-Fyb Require exposure, warm-reacting, IgG, dosage, variable expression Severe HTR, delayed, extravascular Mild HDFN (dosage)

What happens with Duffy incompatible blood?

Severe HTR (delayed, extravascular) Mild HDN (same reasons as for Kidd)

Unique features of Duffy:

1. Fya-b- --> Malarial resistance

• Fya-b- humans are resistant to Plasmodium vivax and Plasmodium knowlesi

2. Dosage

3. Variable expression

What is the frequency of K ag?

9% whites 2% blacks

What is the frequency of k ag?

99.8%

What is Kx's relationship with Kell?

As Kell ag decrease --> Kx increases (may be due to decrease in masking Kell ag) (Kell null) As Kx decreases --> Kell ag decrease too (Kx may be required for proper Kell ag expression) (McLeod phenotype)

What is the possible function of Kx?

May help stabilize the RBC membrane Closely related to K antigens on RBC membrane

What destroys Kell system antigens?

Not enzymes Thiol reagents (2-ME, DTT, ZZAP)

What is the most common non-ABO antibody after anti-D?

Anti-K