IMHM311LEC Immunohematology Lecture PDF

1869 IMHM311LEC: IMMUNOHEMATOLOGY LECTURE Finding a non-toxic anticoagulant WK2: Introduction to Immunohematology Obstetrician Braxton Hicks recommends...

1869 IMHM311LEC: IMMUNOHEMATOLOGY LECTURE Finding a non-toxic anticoagulant WK2: Introduction to Immunohematology Obstetrician Braxton Hicks recommends sodium phosphate 3rd Year 2nd Semester | S.Y. 2022 – 2023 This was perhaps the first example of blood preservation research Instructor: Prof. Earl Joseph D. Catampatan, RMT, MPH 1873-1880 US physicians transfuse milk (from cows, goats, and humans) Milk is used to mitigate infection diseases that contain antibodies 1901 Discovery of ABO Blood Group system Blood Types: Content o A I. Immunohematology o B II. Historical Overview o O III. Genetics-Basic Concepts Discovered by Karl Landsteiner IV. Review of Basic Genetics-Terminologies Landsteiner's Law V. Mendel’s Law of Inheritance Observed in the different blood types as we have naturally producing VI. Law of Independent Segregation antibodies VII. Law of Independent Assortment The presence of the agglutinogen or agglutinin is the one being observed VIII. Inheritance Patterns If an agglutinogen is present on red blood cell membrane, the corresponding IX. Punnett Squares agglutinin (antibody) must be absent in the plasma If an agglutinogen is absent on the red blood cell membrane, then Immunohematology corresponding agglutinin must be present in the plasma Commonly known as blood banking, is a branch of hematology which studies o Heparin: naturally producing anti-coagulant antigen-antibody reactions and analogous phenomena as they relate to the o Agglutinogen: antigen pathogenesis and clinical manifestations of blood disorders o Agglutinin: antibody Preparation of blood and blood components for transfusion as well as Naturally Producing Antibodies: selection of appropriate, compatible components for transfusion ▪ Blood Type B: antibodies are anti-A o Incompatibility of the blood bag to the recipient: antigen-antibody ▪ Blood Type A: antibodies are anti-B reaction happens ▪ Blood Type O: antibodies are anti-A and B ▪ The immune response of the host will be induced signaling that Early 1920’s: this discovery of ABO blood groups by Karl Landsteiner won a there is a foreign material in the body system (transfusion Nobel prize reaction) o Described the serious reaction that occur in human as a result of a ▪ If the transfusion reaction is not immediately resolved it could compatible transfusion be fatal 1902 Study the antibody production by the host when exposed to foreign antigens Discovery of blood type AB (4th blood type) Goal: provision of compatible blood for the patients Von Decastello and Sturli Blood Banking 1907 Refers to the process of collecting, storing, and processing blood and the Ludvig Hektoen: suggests that the safety of transfusion might be improved distribution of RBCs and blood components by crossmatching Objective: fulfilling the purpose of the blood-bag (what is it for) o Still applicated until today for the testing if the blood bag is Transfusion Medicine/ Transfusiology compatible to the recipient Branch of medicine that is concerned with transfusion of blood and blood 1908 components French surgeon Alexis Carrel devises a way to prevent clotting by sewing the vein of the recipient directly to the artery of the donor Historical Overview This vein-to-artery or direct method, known as anastomosis, is practiced by 1492 a number of physicians 1st time a blood transfusion was recorded in history o Blood is directly collected from the needle inserted in the vein Pope Innocent VII received blood from three different individual The procedure proves unfeasible for blood transfusions, but paves the way 1st problem encountered: Clotting was the principal obstacle to overcome for successful organ transplantation, for which Carrel receives the Nobel o Clotting was evident as no anti-coagulants was invented yet Prize in 1912 o Anti-coagulants: chemical substances which reduce/ prevent blood 1908 coagulation Moreschi describes the anti-human globulin test (AHG) reaction (a direct way ▪ Depending onto what kind of anti-coagulant is used is the of visualizing an Ag-Ab reaction that has taken place but is not directly viability of the blood visible) 1867 o AHG reaction: detection of the unknown/ unidentified antibodies English surgeon Joseph Lister uses antiseptics to control infection during o Identifies unknown antibodies to ensure that no reaction will occur in transfusions blood transfusions o To avoid bacterial infection o AHG is also referred to as the Coombs Test o Alcohol and Povidone Iodine: antiseptics used in blood banking o Principle: sensitization of RBCs ▪ Alcohol is applied to disinfect the site of collection then 2 Types of AHG Test: povidone iodine is also applied on the area ▪ Direct: in-vivo sensitization of RBCs ▪ Indirect: in-vitro sensitization of RBCs The Ag-Ab react with each other, then, after washing to remove any unbound antibody, the AHG reagent is added and binds between the Ab that are stuck onto the Ag 1 IMHM311LEC: IMMUNOHEMATOLOGY LECTURE WK2: INTRODUCTION TO IMMUNOHEMATOLOGY 1911 1939-1940 Divided blood group A into 2 subgroups The Rh blood group system is discovered by Karl Landsteiner, Alex Wiener, o A1 Philip Levine, and R.E. Stetson and is soon recognized as the cause of the o A2 majority of transfusion reactions Von Dungern and Hirszfel Rh blood group: rhesus blood group (derived from rhesus monkey) 1912 o Rh blood group → D antigen Roger Lee, a visiting physician at the Massachusetts General Hospital, along 2 types: with Paul Dudley White, develops the Lee-White clotting time. ▪ Rh negative o Lee-White Clotting Time: procedure done to determine the clotting ▪ Rh positive time of a certain patient 1940 o The determination of the clotting time is necessary for patients with Edwin Cohn, a professor of biological chemistry at Harvard Medical School, clotting disorders and for pre-operative procedures develops cold ethanol fractionation, the process of breaking down plasma Lee’s studies lead to the terms "universal donor" and "universal recipient" into components and products (only intended for packed RBCs) Albumin, a protein with powerful osmotic properties, plus gamma globulin and o Universal donor: blood type O rh negative (O-) fibrinogen are isolated and become available for clinical use o Universal recipient: blood type AB Rh positive (AB+) o Crystalloids/ alkaloids: can be used in the place of RBCs in emergency 1913 cases Edward E. Lindemann was the first to succeed to perform blood transfusion o Examples are: albumin, NSS 1914 John Elliott develops the first blood container (vacuum bottle) An unprecedented accomplishment in blood transfusion was achieved 1943 Albert Hustin reported the use of sodium citrate as an anticoagulant solution Loutit and Mollison of England introduced the formula for the preservative for transfusions Acid Citrate Dextrose (ACD) 1915 1945 Lewisohn determined the minimum amount of citrate needed for Coombs, Mourant, and Race describe the use of antihuman globulin (later anticoagulation and demonstrated its nontoxicity in small amounts known as the “Coombs Test”) to identify “incomplete” antibodies o Citrate toxicity: excess amount of citrate will bind to calcium which 1947 will lead to hypocalcemia The American Association of Blood Banks (AABB) is formed to promote Made transfusion medicine more practical and safer for the patient common goals among blood banking practitioners and the blood donating 1916 public Development of preservative solutions to enhance the metabolism of the AABB: agency and primary accreditor which mandates the guidelines, rules, RBC and standards involving transfusion medicine o Purpose of RBCs: deliver oxygen to the body system (tissues/ organs) Publication of the “Journal of Clinical Investigation” o Preservative of RBCs is strictly followed to prevent physically or Hospitals responded immediately, and in 1947, blood banks were established chemically induced transfusion reaction in many major cities of the United States ▪ Transfusion of RBCs which have damaged components/ 1949-1950 morphology will induce the physical or chemical transfusion The US blood collection system includes 1,500 hospital blood banks, 46 reaction community blood centers, and 31 American Red Cross regional blood centers Francis Rous and Turner introduced a citrate-dextrose solution for the 1950 preservation of blood Audrey Smith reports the use of glycerol cryoprotectant for freezing red blood 1927-1947 cells MNSs and P blood group system was discovered Preservation of RBCs is done especially if the blood type is rare MNSs Blood Group: Human Erythrocyte Glycophorin Epitopes Before transfusion the frozen RBCs must be thawed first P Blood Group: identification of blood based on the presence of any of these 1950 three substances P, P 1, and P k antigens on the surface of RBCs Carl Walter and W.P. Murphy, Jr., introduce the plastic bag for blood collection 1930’s (safe and easy preparation of multiple blood components from a single unit RBC membrane was better understood (metabolism, deformability & of whole blood) permeability) Types of Blood Bags for Blood Collection 1932 Single Bag The first hospital-based blood depot is established in a Leningrad hospital Designed for collection, storage and transfusion of whole blood 1937 Double Bag Bernard Fantus, director of therapeutics at the Cook County Hospital in Separation of whole blood into red cell and plasma. Chicago, establishes the first hospital blood bank in the US Triple Bag In creating a hospital laboratory that can preserve and store donor blood, Separation into red cells, platelet concentrate and plasma Fantus originates the term "blood bank” Quadruple Bag World War II (1939-1945): Separation into red cells, platelet concentrate, cryoprecipitate Stimulated blood preservation research because the demand for blood and and plasma plasma increased 1953 Demand for plasma is high due to the war having high number of casualties The AABB Clearinghouse is established, providing a centralized system for as plasma aids in stopping bleeding exchanging blood among blood banks 1941 Today, the Clearinghouse is called the National Blood Exchange Dr. Charles Drew was appointed director of the first American Red Cross Development of the refrigerated centrifuge in 1953 further expedites blood Blood Bank at Presbyterian Hospital component therapy/ fractionation 2 IMHM311LEC: IMMUNOHEMATOLOGY LECTURE WK2: INTRODUCTION TO IMMUNOHEMATOLOGY 1957 1983 The AABB forms its committee on Inspection and Accreditation to monitor Additive solutions extend the shelf life of red blood cells to 42 days the implementation of standards for blood banking 1984 Gibson introduced an improved preservative solution, citrate-phosphate- Human Immunodeficiency Virus (HIV) identified as cause of AIDS dextrose (CPD), which was less acidic and eventually replaced ACD as the Stages of HIV standard preservative used for blood storage o Acute stage: last 2-4 weeks with recurring fever 1958 o Latent stage: very asymptomatic which last from 3-20 years The AABB publishes its first edition of Standards for a Blood Transfusion o Late stage: the stage where significant damage in the immune Service (now titled Standards for Blood Banks and Transfusion Services) system starts to appear (decrease of CD4 cells, natural killer cells) 1959 1985 Max Perutz of Cambridge University deciphers the molecular structure of The first blood-screening test to detect HIV is licensed and quickly hemoglobin, the molecule that transports oxygen and gives red blood cells implemented by blood banks to protect the blood supply their color 1987 1960 Two tests that screen for indirect evidence of hepatitis is developed and The AABB begins publication of TRANSFUSION, the first American journal implemented, hepatitis B core antibody (anti-HBc) and the alanine wholly devoted to the science of blood banking and transfusion technology aminotransferase test (ALT) In this same year, A. Solomon and J.L. Fahey report the first therapeutic These two tests are performed in tandem to determine if the blood have plasmapheresis procedure present HBV 1961 1989 The role of platelet concentrates in reducing mortality from hemorrhage in Human-T-Lymphotropic-Virus-I-antibody (anti-HTLV-I) testing of donated cancer patients is recognized blood begins 1962 1990 The first antihemophilic factor (AHF) concentrate to treat coagulation Introduction of first specific test for hepatitis C, the major cause of “non-A, disorders in hemophilia patients is developed through fractionation non-B” hepatitis Hemophilia: excessive bleeding 1992 1964 Testing of donor blood for HIV-1 and HIV-2 antibodies (anti-HIV-1 and anti- Plasmapheresis is introduced as a means of collecting plasma for HIV-2) is implemented fractionation 1996 1965 HIV p24 antigen testing of donated blood begins. Although the test does not Judith G. Pool and Angela E. Shannon report a method for producing completely close the HIV window, it shortens the window period Cryoprecipitated AHF for treatment of hemophilia HIV p24: marker for detecting the presence of HIV antigen from 11 days – 1 1967 month after exposure/ infection of HIV Rh immune globulin (RHOGAM) is commercially introduced to prevent Rh Determines the percentage of the possibility to make antibodies to the virus disease in the newborns of Rh-negative women 1997 Rh disease: erythroblastosis fetalis/ hemolytic disease of the newborn U.S. Gov’t issues two reports suggesting ways to improve blood safety, o The mother is Rh- and the newborn is Rh+ which then cause the including regulatory reform. National Blood Data Resource Center founded by maternal antibodies to react/ destroy with the fetal cells AABB to collect, analyze and distribute data on all aspects of blood banking o Leads to continuous abortions, miscarriages, and ectopic pregnancy and transfusion medicine 1969 1998 S. Murphy and F. Gardner demonstrate the feasibility of storing platelets at HCV lookback campaign — a public health effort to alert anyone who may room temperature (22°C – 24°C) with continuous agitation, revolutionizing have been exposed to the hepatitis C virus (HCV) through blood transfusions platelet transfusion therapy before July 1992 so they can receive medical counseling and treatment if 1970 needed Blood banks move toward an all-volunteer blood donor system 1999 1971 Blood community begins implementation of Nucleic Acid Amplification Hepatitis B surface antigen (HBsAg) testing of donated blood begins Testing (NAT) under the FDA’s Investigational New Drug (IND) application (screening test) process. NAT employs a testing technology that directly detects the genetic HBV: transmissible virus materials of viruses like HCV 1972 2002 Apheresis is used to extract one cellular component, returning the rest of the West Nile virus identified as transfusion transmissible blood to the donor 2002 1979 Nucleic acid amplification test (NAT) for HIV and HCV was licensed by the A new anticoagulant preservative, citrate phosphate dextrose adenine Food and Drug Administration solution (CPDA-1), extends the shelf life of whole blood and red blood cells 2003 to 35 days First-ever National Blood Foundation forum unites leaders in blood banking Early 1980s and transfusion medicine With the growth of component therapy, products for coagulation disorders, 2003 and plasma exchange for the treatment of autoimmune disorders, hospital FDA issues final guidance regarding “Revised Recommendations for the and community blood banks enter the era of transfusion medicine (doctors Assessment of Donor Suitability and Blood and Blood Product Safety in Cases trained specifically in blood transfusion actively participate in patient care) of Known or Suspected West Nile Virus Infection.” and HIV 1981 2003 First Acquired Immune Deficiency Syndrome (AIDS) case reported First West Nile Virus-positive unit of blood intercepted STIs: sexually transmitted infections 3 IMHM311LEC: IMMUNOHEMATOLOGY LECTURE WK2: INTRODUCTION TO IMMUNOHEMATOLOGY 2003 Law of Independent Assortment Guidance on Implementation of New Bacteria Reduction and Detection States that “genes for different traits are inherited separately from each Standard issued other” 2004 Members of one gene pair separate from one another independently of the AABB receives $2.4 Million CDC grant to reduce transfusion-transmitted HIV member of other gene pairs in Africa and South America This allows for all possible combinations of genes to occur in the offspring 2005 If a homozygote that is dominant for two different characteristics is crossed FDA approves the first West Nile virus (WNV) blood test to screen donors of with a homozygote that is recessive for both characteristics blood, organs, cells and tissues o The F1 generation consists of plants whose phenotype is the same as that of the dominant parent Genetics-Basic Concepts o However, when the F1 generation is crossed in the F2 generation, two general classes of offspring are found Review of Basic Genetics-Terminologies ▪ Parental type: Exact characteristics as the parental generation Genes Are units of inheritance that encode for certain traits or visible ▪ Reciprocal type: mixture of dominant feature and recessive characteristics feature Chromosomes Linear arrangement of genes. Phenotype The phenotype is the physical expression of inherited genes Genotype The set of alleles for a given trait carried by an organism Alleles Alleles are defined as alternative forms of a gene. A portion within the chromosome that codes for the traits/genes Locus (loci) Specific location of genes within the chromosomes Autosomal Inherited on one of the 22 pairs of autosomal chromosomes Sex-linked Genes inherited on the sex-chromosomes (X chromosomes) Dominant A gene that is when expressed whenever the allele is present Recessive A gene that is not expressed even the allele is present. Silent gene can only be expressed if two identical genes are present Codominant A pair of genes in which neither is dominant over the other. Two different genes that are inherited at the same loci on a pair of chromosomes Homozygous Having two identical genes for a given trait Heterozygous Having two unidentical genes for a given trait Mendel’s Law of Inheritance Gregor Mendel An Australian monk and mathematician who used sweet pea plants growing in a monastery garden to study physical traits in organisms and how they are inherited. He studied the inheritance of several readily observable pea plant Inheritance Patterns characteristics, notably flower color, seed color, and seed shape and based The interpretation of pedigree analysis requires the understanding of various his first law of inheritance standard conventions in the representation of data figures Males are always represented by squares and females by circles Law of Independent Segregation A line joining a male and female indicates a mating between the two, and 1st Generation→ “Parental” offspring are indicated by a vertical line o Consisted of all red or all white flowers A double line between a male and female indicates a consanguineous mating o Homozygous for red flower or homozygous for white flower A stillbirth or abortion is indicated by a small black circle First-filial generation→ crossbreed of homozygous red and homozygous Deceased family members have a line crossed through them white flower The propositus in the pedigree is indicated by an arrow pointing to it and Second-filial generation→ crossbreed of First-filial generation indicates the most interesting or important member of the pedigree 4 IMHM311LEC: IMMUNOHEMATOLOGY LECTURE WK2: INTRODUCTION TO IMMUNOHEMATOLOGY Different Inheritance Patterns 1. Autosomal Dominant 2. Autosomal Recessive 3. X-linked Dominant 4. X-linked Recessive Autosomal Dominant Inheritance All the members of a family that carry the allele show the physical characteristic Generally, each individual with the trait has at least one parent with the trait Unlike X-linked traits, autosomal traits usually do not show a difference in the distribution between males and females, and this can be a helpful clue in their evaluation Autosomal Recessive Inheritance “Autosomal” refers to traits that are not carried on the sex chromosomes A recessive trait is carried by either parent or both parents but is not generally seen at the phenotypic level unless both parents carry the trait In some cases, a recessive trait can be genetically expressed in a heterozygous individual but is often not seen at the phenotypic level X-Linked Dominant Inheritance If the father carries the trait on his X chromosome, he has no sons with the trait, but all his daughters will have the trait Women can be either homozygous or heterozygous for an X-linked trait And therefore, when mothers have an X-linked trait, their daughters inherit the trait in a manner identical to autosomal inheritance The sons have a 50 percent chance of inheriting the trait or not Because the trait is dominant, the sons who inherit it will express the trait The XGA blood group system is one of the few blood group systems that follow an X-linked inheritance pattern X-Linked Recessive Inheritance The father always expresses the trait but never passes it on to his sons The father always passes the trait to all his daughters, who are then carriers of the trait In the homozygous state, X’Y, the males will express the trait, whereas only the rare homozygous females, X’X’, will express the trait With an X-linked recessive trait, a disease-carrying gene can be passed from generation to generation with many individuals not affected Punnett Squares A Punnett square illustrates the probabilities of phenotypes from known or inferred genotypes Portrays the potential offspring’s phenotypes or parent’s probable genotype Examples: A B A B A O O AO BO A AA AB O AO OO O AO BO B AB BB O AO OO B B A A A O O BO BO B AB AB A AA AO O BO BO B AB AB O AO OO 5