Blood Bank Lecture 1 Fundamental Concepts

Blood bank primary role

Provide the safest possible blood components to patients

Blood bank tests detect

Red blood cell antigens

Antibodies produced in response to these red cell antigens

Blood bankers job

Ensure compatible blood components are always provided

Introduction to genetics

Genetics is used to understand blood group inheritance and testing for diseases, both of which are important in transfusion medicine

Information on blood group genetics and the inherited differences among individuals forms the foundation of safe blood transfusion

Accurate and sensitive methods of pathogen testing are also important to maintain the safety of the blood supply

Historically blood bankers have been concerned with population genetics and blood group inheritance

Most blood groups follow a straightforward autosomal codominant inheritance pattern

With the increased availability of modern genetic techniques, now we can more readily use genetic test to determine antigen profiles of both donors and recipients

Most blood groups follow what inheritance pattern

Autosomal Codominant

Three different levels of genetics are

Population genetics

Cellular genetics

Molecular genetics

The antigens expressed on blood cells are called

Phenotypes

Phenotypes are controlled by

Genotypes

Population genetics as used in blood banking focuses on

Mendel’s Laws of Inheritance

Hardy-Weinberg EquationTW

The two laws of inheritance are

The Law of Independent Segregation

The Law of Independent Assortment

What is it called when the same allele is on both parental gametes

Homozygous

What is it called when different alleles are on each parental gamete

Heterozygous

Allele pairs separate during the formation of gametes

They do not have a permanent effect on each other

One allele is passed from each parent to each offspring of its own

Law of Independent Segregation

One gene is not dominant over its allele

Both alleles are expressed as their gene products are both seen at the phenotypic level

Different traits are inherited separately from each other

Law of Independent assortment

If two traits are physically near each other on the chromosome, they are considered _____ and may be inherited together as _________

linked; haplotype

Example of Haplotype

M and N alleles and the S and s alleles are physically close on the same chromosome and are inherited as a haplotype

Results in a different prevalence than if inheritance followed random assortment

Linkage disequilibrium

Hardy-Weinberg Principle

p + q = 1

p = frequency of the dominant allele

q = frequency of the recessive allele

Expanded Hardy-Weinberg to address heterozygous populations

p² + 2pq + q² = 1

The population studied must be large

Mating among all individuals must be random

Mutations must not occur in parents or offspring

There must be no migration, differential fertility, or mortality of genotypes studied

In any normal population it is almost impossible to meet all of these criteria. However, the equation is still one of the best tools for studying gene frequencies in human populations

Criteria for use of the Hardy-Weinberg Principle

The frequency of a particular phenotype can be useful in another calculation specific to blood banking.

This formula is used when looking for donor units of red blood cells that are negative for one or more specific antigens, which are most often required for patients with antibodies

This calculation provides an estimates of the number of donor red blood cell units that will need to be tested in order to find the requested number of units with the desired phenotype characteristics

number of units to test = number of units desired/ antigen negative frequency

Phenotype calculations

If more than one antigen needs to be negative, then multiply the antigen negative frequencies of each antigen in the denominator

number of units to test = number of units desired / (antigen negative frequency 1)(antigen negative frequency 2)… and so on

Molecular testing results provide an individuals

Genotype

Molecular Genetics

Biotechnology

Molecular Diagnositcs

Transfusion Medicine and Molecular Biology

The genetic basis for blood group antigens (Single nucleotide polymorphism, SNP)

Gives rise to multiple alleles for a given gene

Polymorphism

Polymorphism refers to what part of transfusion medicine and molecular biology

Molecular genetics

Recombinant proteins

Coagulation factor concentrates vs donor plasma

Biotechnology

Enhanced safety of blood products by narrowing the preseroconversion window

Nucleic Acid Testing

Nucleic Acid Testing

RBC Genotyping

Molecular diagnositcs

Being used more frequently in blood banking

Has not replaced serologic testing but complements it. This is because it is often used to make decisions for obtaining compatible blood by confirming serologic testing or used in cases where serology is not possible or not sensitive enough or where discrepancies occur

RBC genotyping

Fetal DNA typing

Extensive blood group typing of donors

Screening of blood donors for rare phenotypes

Blood group typing for patients with autoimmune hemolytic anemia and other diseases

Resolving blood type discrepancies

Determining blood type of massively transfused patients

Important applications for red blood cell genotyping

Another use for molecular genetics

Often used in cases of disputed paternity

Classical genetic systems used in the past included RBC antigens, but there has been an almost complete switch to DNA polymorphism testing using short tandem repeats (STRs)

Classically, if maternity is assumed, paternity can be excluded by either indirect or direct exclusion

DNA methods usually require 3 mismatches (of alleles between child and alleged father) before concluding an exclusion

Relationship testing

What type of exclusion is it when the child has inherited a genetic marker that is NOT found in the mother or alleged father?

Direct Exclusion

What type of exclusion is it when the child LACKS a genetic marker the alleged father SHOULD have transmitted.

Keep in mind that some alleles have silent genes, genes that do not produce a product

If this method is used, it should not be the only marker used to exclude paternity

Indirect exclusion

Paternity may be excluded based on Kidd typing