Blood Banking Pre Board Exam Review

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  • 🔊NOTES (LAST NAME LECTURER):
    • Notes
  • 🗣Question (Q&A / RECIT during lectures)
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References

  • Notes from discussion by:
    • ALBA, Aleihsa Beatrice
    • ALCAZAR, Jehnn
    • CANOZA, Divine Zionne
    • DELA CRUZ, Albenne Dale
    • NOBLES, Scott Kirk
    • OCTOSO, Angel
    • PAGHARION, Dann Angelo
    • SIOCO, Kate Louise
    • SORIO, Kristy Noreen
  • Books/PDFs/PPTs:
    • Harmening, D. M. (2019). Modern Blood Banking and Transfusion Practices (7th ed.).
    • Besa, J. R. (N.D). Blood Banking Review (Powerpoint Presentation)
    • Batch Hiraya (2022). Blood Banking Preboards Trans
  • LECTURER/s: Ma’am Jena Faith Caras
  • ALBA, ALCAZAR, CANOZA, DELA CRUZ A.D, NOBLES, OCTOSO, PAGHARION, SIOCO, SORIO

Topic Outline

  • Historical overview, Basic Genetics, BB immunology, Blood Groups Introduction
  • ABO Blood Group
  • RH Blood Group
  • Other Major Blood Group
  • Minor Blood Group

Historical Overview

  • 📎 Ancient Egyptians bathed in it
  • 📎 Aristocrats drank it
  • 📎 Authors and playwrights used it as themes
  • 📎 Modern humanity transfuses it

Early Transfusion

  • 1492 — Pope Innocent VII
    • First recorded blood transfusion in history where blood was taken from 3 young men and given to sick Pope Innocent VII in the hope of curing him
    • 📎 He was ill, and the blood was transfused orally. He drank the blood that was drained from the 3 young men which also caused their death
  • 1628 — William Harvey
    • English physician who discovered the circulation of blood
    • Shortly afterward, the earliest known blood transfusion is attempted
    • 📎 A physician, and an anatomist. He was very curious with the circulation, the heart, arteries, veins etc. which had a lot of issues
  • 1665 — Richard Lower
    • First recorded successful canine blood transfusion in England by keeping dogs alive by transfusion of blood from other dogs
    • Between a mastiff and a mixed breed dog. A silver tube was connected to the donor’s artery and the recipient vein
    • 📎 He successfully transfused blood in canine, mastiff, and a mixed breed.
  • 1667 — Jean Baptiste Denis
    • First recorded animal-to-human blood transfusion (Calf blood)
    • Richard Lower - Sheep’s blood
  • 1795 — Philip Syng Physick
    • Unconfirmed first human-to-human transfusion
  • 1818 — James Blundel of England
    • Successful transfusion to woman suffering from postpartum hemorrhage
  • 1840 — Samuel Armstrong Lane
    • At St.George’s school in London, aided by consultant Dr. Blundell, performs the first successful whole blood transfusion to treat hemophilia
    • 📎 With the help of Dr. James Blundell they successfully performed the whole blood transfusion to treat
  • 1867 — Joseph Lister
    • English surgeon, Joseph Lister uses antiseptics, to control infection during transfusion
  • 1873-1880
    • US physician transfuse milk (from cows, goats and humans)
  • 1840
    • Saline infusion replaces milk as a “blood substitute” due to the increased frequency of adverse reactions to milk

Blood Groups

YEARPERSON/S INVOLVEDEVENT
1901Karl Landsteiner● Discovery of ABO Blood group
● “Specificity and Serological reactions”
1902Anthony Decastello and Adriano Sturli● “AB Blood Group”
1907Richard Weil● First to perform ABO typing and began compatibility testing
● First to suggest ABO inheritance
1913Reuben Ottenberg● Perform first blood transfusion using blood typing and crossmatching in New York
1927-1947● Discovery of MNSs and P systems
1939-1940Phillip, Levine (together with Stetson, Landsteiner, and Alex Weiner)● Discovery of Rh Blood group

Blood Storage

YEARPERSON/S INVOLVEDEVENT
1868Braxton Hicks● Recommends sodium phosphate
● Attempts to find nontoxic anticoagulant began and was the first example of blood preservation
1914● Long term anticoagulant, among the
1916Rous and Turner● Used sodium citrate and as an anticoagulant with glucose
1932● First blood bank was established in a Leningrad hospital
1937Bernard Fantus● Established the first hospital blood bank in the united states
1943Loutit and Mollison● Developed acid citrate dextrose (ACD)
1950Audrey Smith● Reported the use of glycerol cryoprotectant for freezing red blood cells
1957Gibson et. al.● Developed citrate-phosphate-dextrose (CPD), CPD eventually replaced ACD and become commonly used preservative by storage of blood/red cells in liquid form
● Shelf life of blood stored in CPD at 2-4C was 21 days
1979● A new anticoagulant preservative, CPDA-1, extends the shelf life of whole blood and red blood cells to 35 days; addition of adenine improved the synthesis of ATP in the stored blood, which prolonged the storage of blood/red cells at 2-4C to 35 days

Blood Derivatives

YEARPERSON/S INVOLVEDEVENT
1940Edwin Cohn● Developed the cold ethanol fractionation process, called cohn fractionation
1961Pool and Shanon● Revolutionized the treatment of hemophilia A
1967● Concentrated Rh immune globulin was introduced commercially
1985● Dry-heated, lyophilized factor VII and IX concentrates became available
1993● Genetically engineered (recombinant) factor VIII became available
1998● Factor IX became available

Blood Component Therapy

YEARPERSON/S INVOLVEDEVENT
1950Walter and Murphy● Introduced the use of plastic bags for glass bottles
1961● Concentrated blood platelets were recognized as useful for the thrombocytopenia
1962● The first antihemophilic factor (AHF) concentrate to treat coagulation disorders in hemophilia patients was developed through fractionation
1964● Plasmapheresis was introduced as a means of collecting plasma for fractionation
1972● Platelets for transfusion were collected by apheresis

Adverse Effects of TTIs

YEARPERSON/S INVOLVEDEVENT
1962Greenwalt et al● Demonstrated leukocyte reduction filters prevented febrile reactions
1970Graw et al● Used irradiation to prevent TA-GVHD
1971● Commercial testing for hepatitis B surface antigen began
1981● First Acquired Immune Deficiency Syndrome (AIDS) case was reported
1983● Transfusion-transmitted HIV was described
1884● Human Immunodeficiency Virus (HIV) was identified as the cause of AIDS
1985● Test for HIV antibody was introduced, FDA approves ELISA
● First blood-screening tests to detect HIV antibody
1987● Two tests that screen for indirect evidence of hepatitis were developed and implemented, hepatitis B core antibody(anti-Hbc) and the alanine aminotransferase test (ALT)
1989● Testing of donated blood for Human-T-lymphocytic Virus-1-antibody (anti-HTLV-1) begins
1990● Testing for hepatitis C became routine
2002● West Nile virus identified as transfusion transmissible

Blood Transfusion

  • 1901 — Karl Landsteiner
    • Discovery of ABO blood group (Specificity of Serological Reactions)
    • Major breakthrough
      • Each individual has a unique blood type
      • How did Karl Landsteiner discover ABO?
        • He got blood from himself and from five other associates and mixed it with the cells and serum, he was performing the forward and the reserve typing.
        • He was an immunologist and was very particular with the antibody and antigen reactions
  • 1902 — Anthony Decastello & Adriano Sturli
    • Type “AB” blood group

Basic Genetics

  • Father of Genetics – Gregor Mendel
  • Genetics - the study of inheritance or the transmission of characteristics from parents to offspring

Levels of Genetics

  • Population
    • Concerning genetic traits in the large number of individuals
  • Cellular
    • Pertains to the cellular organization of genetic material (DNA)
  • Molecular
    • Based on the biochemistry of genes and the structures that support them

Deoxyribonucleic Acid

  • Carries the primary genetic information within chromosomes found in each cell
  • 📎 Composed of two complementary strands. Both in two opposite directions from 5’ to 3’
  • 📎Components of DNA:
    • Deoxyribose
    • 4 Nitrogen bases
      • Pyrimidines: Cytosine and Thymine
      • Purines: Adenine and Guanine
    • Phosphate group
  • 📎 DNA is acidic and attracted to basic substances
  • 📎 Histone is basic. DNA is coiled around histones
  • The central dogma - it is the flow of genetic information which starts with DNA replication and coding of RNA for transcription process

Central Dogma of Molecular Biology

  • 📎 DNA contains genetic information and during translation, genetic information is copied through mRNA.
    • DNA template holds for the production of proteins or peptides
  • 📎 Protein is the basic functional unit of an organism.
  • Transcription takes place in the nucleus. It uses DNA as a template to make an RNA molecule known as messenger RNA (mRNA). The RNA molecule then leaves the nucleus and goes to a ribosome in the cytoplasm, where translation occurs
  • 📎 Translation reads the genetic code in mRNA and makes a protein

Terminologies

  • Genes
    • Smallest unit of inheritance
    • Section of DNA along the chromosome
    • Encode certain traits or visible characteristics called phenotypes.
    • The specific location of a gene on a chromosome is called a locus (plural = loci), and at each locus there may be only one or several different forms of the gene, which are called alleles.
  • Chromosomes
    • Composed of the genetic material chromatin, a complex of the nucleic acid polymer DNA wrapped around highly basic proteins called histones
    • The helical structure of DNA allows a lot of information to be packaged in a very small amount of space.
  • Shape of the DNA
  • Alleles
    • One of two or more alternative genes which may be present at a given locus on a chromosome
    • The presence of two identical alleles results in a homozygous genotype (i.e., AA), and the phenotype is group A blood
    • Type O is expressed through homozygous alleles OO
    • The inheritance of different alleles from each parent gives a heterozygous genotype
DOMINANTRECESSIVE
● Only one allele must be inherited for it to be expressed; gene products are always Present● Same allele must be inherited from both parents to be expressed, homozygous
● RR/Rr = Red colored flower● Rr = Red colored flower
● rr = White colored flower
○ Dominant gene masks the recessive gene○ Recessive genes can only be expressed if both alleles are inherited and expressed or if the dominant gene is absent
  • Genotype vs. Phenotype
GENOTYPEPHENOTYPE
📎The sequence of DNA that is inherited.📎Anything that is produced by the genotype, including an enzyme to control a blood group antigen; the length of long bones of the skeleton etc.
📎Genotype can be determined in molecular level📎The trait that is being expressed
● Set of genes● Observable traits
○ AA vs AB○ Hair color, eye color
  • Reminder: Alleles are forms of same gene with small differences in their sequence
SEROLOGICGENOTYPIC
● Test for RBC agglutination with known antisera● Extracted DNA is analyzed
● Observable expression of RBC antigens● Prediction of antigens based on alleles detected
  • Amorphic Gene
    • A gene with no observable effect, manifestation or product
      • Ex. O gene
      • “Silent gene”
  • Hemizygous
    • Refers to the condition when one chromosome has a copy of the gene and the other chromosome has that gene deleted or absent.
  • Codominant
    • Equal expression of both alleles in phenotype
    • Most of the antigens in the various blood group systems (i.e., ABO, Rh, Kell, Kidd etc.) generally follow straightforward inheritance, usually of a codominant nature
    • 📎 AB genes = A & B antigens in RBCs
  • Polymorphic
    • Having two or more possible alleles at a locus
    • Example: ABO blood group
  • Antithetical
    • Opposite form of a gene, different allele
  • Cis
    • Genes are inherited on the same chromosome
    • Example: C in cis position to D
      • DCe/dce
      • 📎 D expression is not weakened
  • Trans
    • Genes are inherited on separate chromosomes
    • Genes inherited in transposition can weaken the trait’s expression
    • Example: C in trans position to D
      • Dce/dCe
      • 📎 Trans position leads to weak D expression
  • Linked Genes
    • Genes that are close together on a chromosome and inherited as one unit
  • Haplotype
    • Set of genes inherited via one of the parental gametes
  • Dosage
    • A significant difference in antibody reaction strength depending on the quantity of target antigen present on a target red blood cell
    • If an antibody gives a stronger reaction with RBCs double-dosed for the target antigen, it shows the dosage effect
      • 📎If the persons has two Jka genes or homozygous for Jka genes, more Jka antigens are expressed on the rbc surface
        • Reaction expression stronger
      • 📎 If it is heterozygous, Jka and Jkb expression is weakened because binding sites are limited and shared by both Jka and Jkb

Patterns of Inheritance

  • Autosomal Dominant
    • Genes expressed with equal frequency in male and females, on non-sex chromosome
  • Sex-Linked Dominant
    • Carried on the X chromosome; no father-to-son transmission; will be expressed if passed from father to daughter or from mother to son
      • 📎 Father only passes the Y chromosome to the son
      • 📎 If it is an X-linked chromosome, it cannot be passed to the son.
      • 📎 Mother can pass it to the son because it passes the X chromosome.
  • Sex-Linked Recessive
    • Carried on the X chromosome
    • Males inherit it from carrier mothers; traits are exhibited most commonly in males. (e.g., hemophilia A)
    • Females can exhibit the trait but must inherit it from both the carrier mother and affected father

Mendelian Inheritance Principles

  • Law of Independent Segregation
    • The law states that during the formation of a gamete, each gene separates from the other such that each gamete carries one allele for each gene
    • An offspring thus receives a pair of alleles for a trait by inheriting homologous chromosomes from the parent organisms: one allele for each trait from each parent
    • Hence, two members of a gene pair segregate from each other during meiosis; each gamete has an equal probability of obtaining either member of the gene
  • Law of Independent Assortment
    • Mendel’s law of Independent Assortment states that when the parent differ from each other in two or more pairs of contrasting characters, the inheritance of one pair of characters is independent of the other
    • The law states that all transfer of a particular character from parents to the offspring remains unaffected by the other characters.
    • The law indicates that the alleles of different genes are assorted into gametes independently of one another.
    • Traits inherited from different chromosomes expressed separately and discretely.
  • Law of Dominance
    • If the two alleles of an inherited pair differ (the heterozygous condition), then one determines the organism’s appearance and is called the dominant allele, the other has no noticeable effect on the organism’s appearance and is called the recessive allele
    • Thus, the dominant allele will hide the phenotypic effects of the recessive alleles
    • Recessive alleles will always be masked by dominant alleles

Hardy-Weinberg Principle

  • Mathematical formula that allowed the study of mendelian inheritance in great detail
  • p+q = 1
  • Where:
    • p – the gene frequency of the dominant allele
    • q – the frequency of the recessive allele
    • Can also be stated as: p^2 + 2pq + q^2 = 1
    • For bigger population and ideal conditions

Punnett Square

  • The inheritance of blood group antigen (A, B, O) can be predicted using a Punnett square
  • A way to predict a trait or genotype that comes from two different people or organism

Practice Exercise

  • 1. Given: Genotype of Parent 1 (bb) and Parent Bb
    • a.) 50% chance that the homozygous recessive trait will be shown on the next kid
    • b.) 50% chance that the heterozygous dominant trait is given on the next offspring
    • c.) No or Negative chance of passing homozygous dominant trait to offspring
  • 2. Draw a punnett square with AB female parent and the O male parent
    • A - 50%
    • B - 50%

Blood Bank Immunology

  • Serologic, genetic, biochemical, and molecular study of antigens associated with membrane structures on the cellular constituents of blood, as well as the immunologic properties and reactions of blood components. (Henry, 2011)
  • Immunohematology is the study of the reactions that take place between antigens present on red blood cells and antibodies present in plasma
  • Patients undergoing transfusion therapy are tested for their ABO and RhD blood groups and the presence of any antibodies that may cause a reaction between their plasma and donor red cells.
  • December 2022, ISBT recognized 44 blood group systems containing 354 red cell antigens
  • As of July 2023, ISBT have 45 blood group, 360 red cell antigens

Immune System

INNATE OR NATURALACQUIRED OR ADAPTIVE
● Nonspecific primitive IS● The specific, evolved IS
● Humoral, mediated by B cells and antibody production
● Cellular, mediated by T cells and lymphokines

Characteristics of an Antigen

  • Antigens are substances that combine with antibody
  • Antigen that causes a specific immune response is an immunogen
  • 30 RBC antigen systems, containing over 300 RBC antigens

| | | |
| :-------------- | :- | :- |
| Proteins | | Rh, M and N |
| Glycolipids | | ABH, Lewis, Li and P |
| Glycoproteins | | HLA |

  • Antigens are not limited to RBCs (can also present in secretions and tissue)

Characteristics of Blood Group Antibodies

NATURALLY OCCURINGIMMUNE ANTIBODIES
● Nonspecific primitive IS● The specific, evolved IS
● Humoral, mediated by B cells and antibody production● Cellular, mediated by T cells and lymphokines

Basic Structure of an Antibody


  • Composed of two heavy chains and two light chains

FAB DOMAINFc Domain
● Antigen-binding site● Constant region
● Variable region specific for one single epitope/antigen● When Fab portion binds to antigen, Fc portion activates effector mechanisms (complement activation, phagocytosis, lysis, etc.,)

Antibody Isotypes

  • Five different antibody isotypes
  • Differences in:
    • Heavy chains
    • Binding affinity and avidity
    • Ability to activate complement
    • Ability to cross the placenta
  • Most blood group antibodies are either IgG or IgM

Characteristics of IgG and IgM Antibodies

IgMIgG
● High avidity (binds strongly to antigen) due to pentamer● Monomer: does not usually agglutinate
● Ten antigen binding sites per molecule● RBCs directly
● Direct agglutination of RBCs● Example: Most clinically significant alloantibodies, like anti-c or anti-K
● Example: ABO antibodies
In the blood bank, IgM antibodies…In the blood bank, IgG antibodies…
● React at <22°C / Agglutination at immediate spin (IS)● Generally, don't directly agglutinate / no reactivity at IS
● Often not