GROUP 4 C1

OUTLINE
I. Introduction A. Definition of Terms B. The Discovery of ABO Blood Group II. The Red Blood Cell A. Definition B. Function C. Cell Membrane and its Composition 1. Major Integral Proteins 2. Peripheral Membrane Proteins 3. Deformability 4. Permeability III. Blood group Systems A. ABO Blood Group System B. ABH Antigens 1. Formation of H Antigen 2. Formation of A Antigen 3. Formation of B Antigen C. Genetics in Determining Blood Type IV. ABO Typing A. Blood typing B. Blood Transfusion C. Transfusion Reactions

Definition of Terms
Antigen: A substance recognized by the body as being foreign, which can cause an immune response. Antigens are usually, but not exclusively, found on the red blood cell membrane. Antibody: A protein substance secreted by plasma cells that is developed in response to, and interacting specifically with, an antigen. Naturally occuring antibody: antibody present in a patient, without known prior exposure to the corresponding red blood cell antigen.

Definition of Terms
Agglutinogen: A substance that stimulates the production of an agglutinin, thereby acting as an antigen. Agglutinin: An antibody that agglutinates cells. Agglutination: The clumping together of red blood cells or any particulate matter resulting from interaction of antibody and its corresponding antigen.

Definition of Terms
Blood group: The type or specification of an individuals blood according to the presence or absence of specific agglutinogens on the red cells Blood transfusion: The introduction of blood from one person into the circulation of another person Incompatibility: When the agglutinogens on the red cells in the donor react with the agglutinins in the recipients blood.

Definition of Terms
Glycosyltransferases: are enzymes that facilitate the transfer of carbohydrate molecules onto carbohydrate precursor molecules. Immunodominant sugar: in reference to glycoprotein or glycolipid antigens, the sugar molecule that gives the antigen its specificity (e.g. galactose, which confers B antigen specificity).

Definition of Terms
Amorph: a gene that does not appear to produce a detectable antigen; a silent gene such as Jk, Lu, O. Allele: One of two or more different genes that may occupy a specific locus in a chromosome. Locus: the site of a gene at a chromosome.

Definition of Terms
Forward typing/grouping: defined as using known sources of commercial antisera (anti-A, anti-B), to detect antigens on an individuals RBCs. Reverse typing/grouping: defined as detection of ABO antibodies in the patients serum by using known reagent RBCs; namely A1 and B cells.

The Discovery of ABO Blood Group System

Alfred von Decastello Adriano Sturli

Karl Landsteiner

THE RED BLOOD CELL

RED BLOOD CELL

One of the 3 formed elements of blood Produced in the red bone marrow : erythropoiesis

RBC: Structural Characteristics

Biconcave disc Mature RBC: non-nucleated No intracellular organelles such as lysosomes, mitochondria or Golgi apparatus Size:
- Mean diameter: 7.8 micrometers - Thickness: 2.5 micrometers (thickest point), 1 micrometer (center)

RBC: Functions
Major Function: Transport of hemoglobin (red, oxygencontaining pigment) into circulation Also contains carbonic anhydrase which helps in catalyzing carbonic acid (produced by tissues) to carbon dioxide and water for CO2 transport to excretion (exhalation). Responsible for most of the acid-base buffering power of the whole blood.

RBC: Cell Membrane

RBC: Cell Membrane

Table 527. Summary of Biochemical Information About the Membrane of the Human Red Blood Cell (Harpers Illustrated Biochemistry 28th ed.)

The membrane is a bilayer composed of about 50% lipid and 50% protein. The major lipid classes are phospholipids and cholesterol; the major phospholipids are phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) along with sphingomyelin (Sph). The choline-containing phospholipids, PC and Sph, predominate in the outer leaflet and the amino-containing phospholipids (PE and PS) in the inner leaflet. Glycosphingolipids (GSLs) (neutral GSLs, gangliosides, and complex species, including the ABO blood group substances) constitute about 510% of the total lipid.

RBC: Cell Membrane

RBC MEMBRANE PROTEINS

Integral Proteins Glycophorin A Glycophorin B Glycophorin C Anion-exchange-channel protein (Band 3) Peripheral Proteins Spectrin Actin (Band 5) Ankyrin (Band 2.1) Band 4.1 and 4.2 Adducin

RBC: Cell Membrane

Integral Proteins
Anion exchange protein (band 3)
- a transmembrane glycoprotein, with its carboxyl terminal end on the external surface of the membrane and its amino terminal end on the cytoplasmic surface.

Integral Proteins
Glycophorins A, B and C - also transmembrane glycoproteins but of the single-pass type, extending across the membrane only once - A is the major Glycophorin

Peripheral Proteins
Spectrin - Major protein of the cytoskeleton composed of 2 polypeptides: spectrin 1 and spectrin 2 - Has 4 binding sites: (1) for self-association, (2) for ankyrin (bands 2.1, etc), (3) for actin (band 5), and (4) for protein 4.1.

Peripheral Proteins
Ankyrin - Pyramid shaped protein that binds spectrin

Peripheral Proteins
Actin (Band 5) - Exists in RBC as short, double helical fragments of F-actin - The tail end of Spectrin dimers binds to actin - Actin also binds with Protein 4.1

Peripheral Proteins
Protein 4.1 - a globular protein, binds tightly to the tail end of spectrin, near the actin-binding site of the latter, and thus is part of a protein 4.1-spectrinactin ternary complex. - Protein 4.1 also binds to the integral proteins, glycophorins A and C, thereby attaching the ternary complex to the membrane. In addition, protein 4.1 may interact with certain membrane phospholipids, thus connecting the lipid bilayer to the cytoskeleton.

BLOOD GROUP SYSTEM

Blood Group System

There are approximately 30 human blood group systems have been recognized, but the best known of which are the ABO, Rh (Rhesus), and MN systems and the most important is the ABO blood group. The term "blood group" applies to a defined system of red blood cell antigens (blood group substances) controlled by a genetic locus having a variable number of alleles (eg, A, B, and O in the ABO system) while the term "blood type" refers to the antigenic phenotype, usually recognized by the use of appropriate antibodies.

ABO Blood Group System

The most important in assuring a safe blood transfusion.

The table shows the four ABO phenotypes ("blood groups") present in the human population and the genotypes that give rise to them.

Blood Antigens Group on RBCs A B AB O A B A and B Neither

Antibodies in Serum

Genotypes

Anti-B Anti-A Neither Anti-A and anti-B

AA or AO BB or BO AB OO

ABH ANTIGENS
Glycolipid in nature Oligosaccharides attached directly to lipids on cell membrane The A and B antigens are the last sugar added to the chain The "O" antigen is the lack of A or B antigens but it does have the most amount of next to last terminal sugar that is called the H antigen.

Formation of ABH Antigens

results from the interaction of genes at three separate loci (ABO, Hh, and Se) Genes produce specific GLYCOSYLTRANSFERASES that add sugars to the basic precursor substance

Gene

Glcosyltransferase

Immunodominant sugar

Antigen

L- fucosyl transferase

L-fucose

N acetylgalactosaminyl transferase

N-acetyl-Dgalactoseamine

D- galactosyl transferase

D-galactose

Formation of ABH Antigens : Precursor Substance

Type 2 Terminal galactose attached to N-acetylglucosamine in a beta 1 4 linkage

Formation of ABH Antigens : H Antigen

H gene

-2-L-fucosyltransferase

L-fucose

Formation of ABH Antigens : A Antigen

A gene

-3-N-acetylgalactosaminyltransferase

N-acetyl-D-galactosamine (GalNAc)

Formation of ABH Antigens : B Antigen

B gene

-3-galactosyltransferase

D-galactose

Genetics in Determining Blood Type

The ABO gene is autosomal (the gene is not on either sex chromosomes) The ABO gene locus is located on the chromosome 9 A and B blood groups are dominant over the O blood group Each person has two copies of genes coding for their ABO blood group (one maternal and one paternal in origin)

1 = A/A 1 = Homozygous A Phenotype A Genotype A/A Can Contribute Only an A Gene to Offspring

2 = A/O 2 = Heterozygous A Phenotype A Genotype A/0 Can Contribute A or O Gene to Offspring

Inheritance Patterns
A/A parent can only pass along A gene A/O parent can pass along either A or O gene B/B parent can only pass along B gene B/O parent can pass along either B or O gene O/O parent can only pass along O gene AB parent can pass along either A or B gene

ABO Groups of the Offspring from the Various Possible ABO Matings
Mating Phenotypes AxA Mating Genotypes AA x AA AA x AO AO x AO BB x BB BB x BO BO x BO AB x AB OO x OO AA x BB AO x BB AA x BO AO x BO AA x OO AO x OO AA x AB AO x AB BB x OO BO x OO BB x AB BO x AB AB x OO Offspring Possible Phenotypes and Genotypes A(AA) A(AA or AO) A(AA or AO) or O (OO) B(BB) B(BB or BO) B(BB or BO) OR O(OO) AB(AB) or A (AA) or B (BB) O (OO) AB (AB) AB (AB) or B (BO) AB (AB) or A (AO) AB (AB) or A (AO) or B (BO) or O (OO) A (AO) A (AO) or O (OO) AB (AB) or A (AA) AB (AB) or A (AA or AO) or B (BO) B (BO) B (BO) or O (OO) AB (AB) or B (BB) AB (AB) or B(BB or BO) or A (AO) A (AO) or B (BO)

BxB

AB x AB OxO AxB

AxO A x AB BxO B x AB AB x O

BLOOD TYPING

Blood Typing
Method to tell what specific type of blood an individual has Blood is often grouped according to the ABO blood typing system. This method breaks blood types down into four categories: Type A Type B Type AB Type O

2 Methods of Blood Typing

Routine ABO Typing

Forward Grouping Reverse Grouping

Reaction of Cells Tested Red Cell ABO With Group
Anti-A 0 + 0 + Anti-B 0 0 + + O A B AB

Reaction of Serum Tested Against

A1 Cells + 0 + 0 B Cells + + 0 0

Reverse ABO Group

O A B AB

Forward Blood Grouping Reactions

Type O Reaction

Type A Reaction

Type B Reaction

Type AB Reaction

BLOOD TRANSFUSION
determination of the patients correct ABO group is the most critical pre transfusion serologic test cross-matching must be done between Patients serum and Donors RBCs and vice versa For a blood transfusion to be successful ABO and Rh blood groups must be compatible between the donor blood and the patient blood

Who can receive blood from whom?

People with blood group 0 Rh - are called "universal donors" and people with blood group AB Rh+ are called "universal receivers.

Red Blood Cell Compatibility Table

Recipient[1 O O O+ A A+ B B+ AB AB+ Table note Assumes absence of atypical antibodies that would cause an incompatibility between donor and recipient blood, as is usual for blood selected by cross matching. O+ A Donor[1] A+ B B+ AB AB+

TRANSFUSION REACTIONS

diverse group of adverse reactions to transfusion that usually present during or shortly after transfusion

Febrile Nonhemolytic Reactions

rise in temperature of 1C or greater chills or rigors

Allergic Reactions
Mild allergic reactions to transfusion are common symptoms include pruritus, urticaria, erythema, and cutaneous flushing

Severe Allergic or Anaphylactic Reactions

manifest cardiovascular instability Hypotension Tachycardia loss of consciousness cardiac arrhythmia Shock cardiac arrest

Acute Hemolytic Reactions (AHTRs)

present within 24 hours of transfusion Intravascular hemolysis is much more common in acute hemolytic reactions than extravascular hemolysis Signs: fever and chills, nausea, vomiting, pain, dyspnea, tachycardia, hypotension, bleeding, and hemoglobinuria Fever may be the initial sign of an AHTR Renal failure is a later complication

Delayed Hemolytic Reactions (DHTRs)

occur at least 24 hours after transfusion of the offending unit due to an anamnestic response to a red cell antigen to which the patient has previously made an antibody, the concentration of which was too low to detect in pretransfusion testing hemolysis is extravascular, but intravascular hemolysis may occur also less severe than AHTRs clinical signs: fever or chills, jaundice, pain, or dyspnea

Bacterial Contamination of Blood Components

When the donors blood is contaminated with large numbers of living organisms Often caused by psychrophilic organisms onset of symptoms in most cases is during the transfusion or shortly after it Signs: Fever, chills, hypotension, shock, nausea, and vomiting Dyspnea, pain, and diarrhea may occur also

Transfusion-associated Circulatory Overload

Too common and preventable transfusion reaction presents as congestive heart failure during or shortly after transfusion Signs and symptoms: dyspnea, orthopnea, cyanosis, tachycardia, elevated blood pressure, pulmonary edema, jugular venous distention, pedal edema, and headache patients with pre-existing heart disease are at risk of circulatory overload with transfusion

Transfusion-Transmitted Diseases
HIV/AIDS Hepatitis Human T Cell Lymphotropic Virus (HTLV I/II) Cytomegalovirus Malaria Syphilis

References
Harpers Illustrated Biochemistry 28th ed. Modern Blood Banking and Transfusion Practices (Denise M. Harmening) 5th ed. Medical Physiology (Guyton and Hall) 11th ed. Henrys Clinical Diagnosis and Management by Laboratory Methods

THANK YOU

APPENDICES

ABO Blood Types