IMHM311 Lec - Week 2: Introduction to Immunohematology PDF

WEEK 2: INTRODUCTION TO IMMUNOHEMATOLOGY IMHM311 LEC 2ND SEMESTER | A.Y.: 2024-2025 | PROF. EARL JOSEPH D. CATAMPATAN, RMT, MPH IMMUNOHEMATOLOGY...

WEEK 2: INTRODUCTION TO IMMUNOHEMATOLOGY IMHM311 LEC 2ND SEMESTER | A.Y.: 2024-2025 | PROF. EARL JOSEPH D. CATAMPATAN, RMT, MPH IMMUNOHEMATOLOGY LANDSTEINER’S LAW commonly known as BLOOD BANKING, is a branch of hematology which If an agglutinogen (antigen) is present on red blood cell membrane, the studies antigen-antibody reactions and analogous phenomena as they corresponding agglutinin (antibody) must be absent in the plasma. relate to the pathogenesis and clinical manifestations of blood disorders. If an agglutinogen is absent on the red blood cell membrane, then ○ Main objective: to have a 0% error or safe transfusion practices corresponding agglutinin must be present in the plasma. ○ Unexpected alloantibodies may interfere in both recipient and We have naturally producing antibodies donor sample Example: (ABO reverse typing) Preparation of blood and blood components for transfusion as well as ○ Blood type B – anti-A is present Cantibody A) selection of appropriate, compatible components for transfusion. ○ Blood type A – anti-B is present Study the antibody production by the host when exposed to foreign ○ Blood type O – anti-A and anti-B antigens. Heparin - Natural anticoagulant in blood BLOOD BANKING DATE DISCOVERY Von Decastello and Adriano Sturli discovered the blood 1902 refers to the process of collecting, storing, and processing blood and the type AB (4th blood type to be discovered) distribution of RBCs and blood components. G - Ludvig Hektoen suggests that the safety of transfusion ○ Proper distribution to avoid having expired blood components and might be improved by crossmatching. to ensure that blood components are always available in the lab ○ Major crossmatching - testing patient’s serum ○ Properly label and accurately submit the products to the physician against the donor’s red cell 1907 ○ Minor crossmatching - testing donor’s serum or nurses within the given time against the patient’s red cell TRANSFUSION MEDICINE ○ Autocontrol - both the patient’s serum and red cell will be tested branch of medicine that is concerned with transfusion of blood and French surgeon Alexis Carrel devises a way to prevent blood components. clotting by sewing the vein of the recipient directly to the ○ Also known as transfusiology artery of the donor. This vein-to-artery or direct method, known as anastomosis, is practiced by a number of physicians. HISTORICAL OVERVIEW The procedure proves unfeasible for blood transfusions, but paves the way for successful organ transplantation, for which Carrel receives the Nobel Prize in 1912 DATE DISCOVERY Moreschi describes the AHG reaction (a direct way of first time a blood transfusion was recorded in history. visualizing an Ag-Ab reaction that has taken place but is - Pope Innocent VII received blood from three different 1908 not directly visible) O 1492 individual. O “Clotting was the principal obstacle to overcome” ○ Because there are no preservatives for a specific ○ AHG test is also known as the Coombs test The Ag-Ab react with each other, then, after washing to remove any unbound antibody, the AHG reagent is added blood product during that time and binds between the Ab that are stuck onto the Ag English surgeon- Joseph Lister uses antiseptics to control Principle of AHG test is through sensitization of RBC ○ Associated with incomplete, unknown, infection during transfusions. ○ Donor bleeding = process of collecting blood weakly-reacting or non-agglutinating antibodies 1867 Two types of AHG testing: sample ○ Common antiseptic technique: application of ○ Direct AHG test – in vivo sensitization alcohol and povidone-iodine ○ Indirect AHG test – in vitro sensitization finding a non-toxic anticoagulant divided blood group A into 2 subgroups: - Braxton Hicks recommends sodium phosphate 1911 ○ - A1 cells and A2 cells – these two are the check cells 1869 for the reverse blood typing of a specific blood type This was perhaps the first example of blood preservation research It was introduced by Von Dungern and Hirszfel - US physicians transfuse milk (from cows, goats, and Roger Lee, a visiting physician at the Massachusetts humans) General Hospital, along with Paul Dudley White, develops 1873-1880 the Lee-White clotting time. ○ The following animals are believed to have the immunoglobulins to treat certain diseases ○ Test that detects coagulation diseases which measures the time of blood clotting (fibrin clot) Karl Landsteiner discovered the ABO Blood Group system 1912 Lee’s studies lead to the terms "universal donor" and Most significant year for transfusion medicine "universal recipient". 1901 He explained the serious reactions that occur in humans ○ universal donor – packed RBCs type O rh negative as a result of incompatible transfusions. His work in the ○ universal recipient – packed RBCs type AB rh beginning of the 20th century won a Nobel Prize. positive BERNARDINO | LUCAS | MAMHOT | ORBASE  WEEK 2: INTRODUCTION TO IMMUNOHEMATOLOGY IMHM311 LEC 2ND SEMESTER | A.Y.: 2024-2025 | PROF. EARL JOSEPH D. CATAMPATAN, RMT, MPH DATE DISCOVERY the preservative acid-citrate-dextrose (ACD) Edward E. Lindemann was the first to succeed to perform Coombs, Mourant, and Race describe the use of 1913 blood transfusion. 1945 antihuman globulin (later known as the “Coombs Test”) to ○ - Used multiple syringes and special cannula identify “incomplete” or unknown antibodies. An unprecedented accomplishment in blood transfusion The American Association of Blood Banks (AABB) is was achieved in 1914 formed to promote common goals among blood banking 1914 Albert Hustin reported the use ofG sodium citrate as an practitioners and the blood donating public. anticoagulant solution for transfusions ○ Association for the Advancements of Blood and Biotherapy Lewisohn determined the minimum amount of citrate 1947 Publication of the “Journal of Clinical Investigation” needed for anticoagulation and demonstrated its ○ Guideline book nontoxicity in small amounts. Hospitals responded immediately, and in 1947, blood ○ Massive transfusion - dependent in blood banks were established in many major cities of the United O - transfusion 1915 States ○ decreased level of ionized calcium ➞ O citrate Ctoxicity ➞ tingling sensation or numbness around The US blood collection system includesG 1,500 hospital the mouth 1949-1950 blood banks, 46 community blood centers, and 31 Blood transfusion became more practical and safer for the American Red Cross regional blood centers. patient Audrey Smith reports the use of G & glycerol cryoprotectant Development of preservative solutions to enhance the for freezing red blood cells metabolism of the RBC. ○ Aside from glycerol, they also used glucose and Francis Rous and Turner introduced a citrate-dextrose urea to prevent water loss and cell damage of the 1916 solution for the preservation of blood. 1950 RBCs ○ PCITR - physically or chemically induced transfusion Carl Walter and W.P. Murphy, Jr., introduce the plastic bag reactions for blood collection (safe and easy preparation of multiple ○ RBC function: to increase oxygen mass blood components from a single unit of whole blood) 1927-1947 MNSs and P blood group system was discovered RBC membrane was better understood (metabolism, BLOOD BAGS 1930’s deformability & permeability) ○ To avoid PCITR Whole blood The first hospital-based blood depot is established in a 450 mL - 63 mL anticoagulant Leningrad hospital. 500 mL - 70 mL anticoagulant Blood bank facilities: 1932 ○ Hospital Blood Bank In a 110-pound normal individual, the maximum blood capacity is up to ○ Blood Center 525 mL blood bag volume ○ Transfusion Services Bernard Fantus, director of therapeutics at the Cook SINGLE BAG DOUBLE BAG County Hospital in Chicago, establishes the first hospital Designed for collection, storage and Separation of whole blood into red blood bank in the US. transfusion of whole blood cell and plasma 1937 In creating a hospital laboratory that can preserve and store donor blood, Fantus originates the term "blood bank." stimulated blood preservation research because the World demand for blood and plasma increased. War II 1941: Dr. Charles Drew was appointed director of the first 1939-1945 American Red Cross Blood Bank at- Presbyterian Hospital The Rh blood group system is discovered by Karl Landsteiner, Alex Wiener, Philip Levine, and R.E. Stetson 1939-1940 and is soon recognized as the cause of the majority of TRIPLE BAG QUADRUPLE BAG transfusion reactions. Separation into red cells, platelet Separation into red cells, platelet Edwin Cohn, a professor of biological chemistry at Harvard concentrate and plasma concentrate, cryoprecipitate (10-15 Medical School, develops- cold ethanol fractionation, the mL;FFP) and plasma process of breaking down plasma into components and products such as albumin, gamma globulin, fibrinogen, antibody etc. 1940 Albumin, a protein with powerful osmotic properties, plus gamma globulin and fibrinogen are isolated and become available for clinical use. John Elliott develops the first blood container (vacuum bottle/vacutainer tubes). 1943 Loutit and Mollison of England introduced the formula for BERNARDINO | LUCAS | MAMHOT | ORBASE WEEK 2: INTRODUCTION TO IMMUNOHEMATOLOGY IMHM311 LEC 2ND SEMESTER | A.Y.: 2024-2025 | PROF. EARL JOSEPH D. CATAMPATAN, RMT, MPH DATE DISCOVERY Blood banks move toward an all-volunteer blood donor 1970 system. The AABB Clearinghouse is established, providing a centralized system for exchanging blood among blood Hepatitis B surface antigen (HBsAg) testing of donated 1971 banks blood begins 1953 Today, the Clearinghouse is called the- National Blood Apheresis is used to extract one cellular component, Exchange C 1972 returning the rest of the blood to the donor. Development of the refrigerated centrifuge in 1953 further expedites blood component therapy A new anticoagulant preservative, CPDA-1, extends the shelf life of whole blood and red blood cells to& 35 days. The AABB forms its committee on Inspection and 1979 ○ CPDA-1 - Citrate phosphate dextrose adenine-1 Accreditation to monitor the implementation of ○ CPDA-2 - shelf life of 42 days standards for blood banking. 1957 Gibson introduced an improved preservative solution, With the growth of component therapy, products for citrate-phosphate-dextrose (CPD), which was less coagulation disorders, and plasma exchange for the acidic and eventually replaced ACD as the standard Early treatment of autoimmune disorders, hospital and preservative used for blood storage. 1980s community blood banks enter the era of transfusion medicine (doctors trained specifically in blood The AABB publishes its first edition of Standards for a transfusion actively participate in patient care) 1958 Blood Transfusion Service (now titled Standards for Blood Banks and Transfusion Services) First Acquired Immune Deficiency Syndrome (AIDS) 1981 case reported. Max Perutz of Cambridge University deciphers the 1959 molecular structure of hemoglobin, the molecule that Additive solutions extend the shelf life of red blood transports oxygen and gives red blood cells their color. cells to 42 days. g 1983 ○ Adsol The AABB begins publication of TRANSFUSION, the first ○ Nutricel American journal wholly devoted to the science of ○ Optisol blood banking and transfusion technology. In this same year, A. Solomon and J.L. Fahey report the Human Immunodeficiency Virus (HIV) identified as 1984 first therapeutic plasmapheresis procedure cause of AIDS ○ Apheresis - a special collection technique in blood bank, deals with specific cellular The first blood-screening test to detect HIV is licensed 1960 1985 and quickly implemented by blood banks to protect the component ○ Applications of Apheresis: blood supply. Component Collection - donation of a Two tests that screen for indirect evidence of hepatitis specific cellular component are developed and implemented, hepatitis B core Therapeutic Procedure - management 1987 antibody (anti-HBc) and the alanine aminotransferase and therapy for a certain clinical test (ALT) disorder Human-T-Lymphotropic-Virus-I-antibody (anti-HTLV-I) The role of platelet concentrates in reducing mortality 1989 1961 testing of donated blood begins. from hemorrhage in cancer patients is recognized. Introduction of first specific test for hepatitis C, the The first antihemophilic factor (AHF) concentrate to 1990 major cause of “non-A, non-B” hepatitis. 1962 treat coagulation disorders in hemophilia patients is developed through fractionation. Testing of donor blood for HIV-1 and HIV-2 antibodies (anti-HIV-1 and anti-HIV-2) is implemented Plasmapheresis is introduced as a means of collecting 1992 1964 ○ HIV 1 - Worldwide plasma for fractionation ○ HIV 2 - West Africa Judith G. Pool and Angela E. Shannon report a method HIV p24 antigen testing of donated blood begins. 1965 for producing cryoprecipitated AHF for treatment of Although the test does not completely hemophilia and extend its shelf life. ○ Applicable for individuals who are recently 1996 Rh immune globulin is commercially introduced to affected by the virus prevent Rh disease in the newborns of Rh-negative ○ Accurate up to 11 days up until 1 month of women. being infected ○ Rh disease occurs during 2nd pregnancy U.S. Gov’t issues two reports suggesting ways to 1967 Rh immune globulin is now called as RHOGAM improve blood safety, including regulatory reform. ○ 300 um dose 1997 National Blood Data Resource Center founded by AABB ○ The risk of sensitization of administration of to collect, analyze and distribute data on all aspects of Rhogam is at delivery blood banking and transfusion medicine. S. Murphy and F. Gardner demonstrate the feasibility of storing Platelets at room temperature, revolutionizing E HCV lookback campaign — a public health effort to alert anyone who may have been exposed to the platelet transfusion therapy. 20-2400with contins is 1998 hepatitis C virus (HCV) through blood transfusions 1969 Why do we need to agitate platelets: before July 1992 so they can receive medical counseling ○ To maintain pH of the cell and treatment if needed. ○ To facilitate oxygen within the cell ○ To prevent platelet aggregation Blood community begins implementation of Nucleic 1999 Acid Amplification Testing (NAT) under the FDA’s BERNARDINO | LUCAS | MAMHOT | ORBASE  WEEK 2: INTRODUCTION TO IMMUNOHEMATOLOGY IMHM311 LEC 2ND SEMESTER | A.Y.: 2024-2025 | PROF. EARL JOSEPH D. CATAMPATAN, RMT, MPH Investigational New Drug (IND) application process. MENDEL’S LAW OF INHERITANCE NAT employs a testing technology that directly detects the genetic materials of viruses like HCV and HIV. ○ NAT - gold standard GREGOR MENDEL West Nile virus identified as transfusion transmissible. Father of genetics 2002 Nucleic acid amplification test (NAT) for HIV and HCV an Australian monk and mathematician who used sweet pea plants was licensed by the Food and Drug Administration. growing in a monastery garden to study physical traits in organisms and First-ever National Blood Foundation forum unites how they are inherited. leaders in blood banking and transfusion medicine He studied the inheritance of several readily observable pea plant FDA issues final guidance regarding “Revised characteristics, notably flower color, seed color, and seed shape and Recommendations for the Assessment of Donor based his first law of inheritance. Suitability and Blood and Blood Product Safety in Cases of Known or Suspected West Nile Virus Infection.” LAW OF INDEPENDENT SEGREGATION 2003 First West Nile Virus-positive unit of blood intercepted. Guidance on Implementation of New Bacteria C 1st Generation ➞ “Parental” (P1) Reduction and Detection Standard issued ○ Consisted of all red or all white flowers Most commonly encountered bacteria in processing Homozygous for red flower or blood products: Homozygous for white flower ○ E. coli First-filial generation (2nd generation) ➞ crossbreed of homozygous red ○ Pseudomonas spp. ○ Yersinia enterocolitica and homozygous white flower Second-filial generation (3rd generation) ➞ crossbreed of First-filial AABB receives a $2.4 Million CDC grant to reduce generation 2004 transfusion-transmitted HIV in Africa and South America. FDA approves the first West Nile virus (WNV) blood 2005 test to screen donors of blood, organs, cells and tissues BASIC CONCEPTS OF GENETICS TERMINOLOGIES Are units of inheritance that encode for certain traits or Genes visible characteristics Chromosomes linear arrangement of genes GPhenotype Genotype is the physical expression of inherited genes The set of alleles for a given trait carried by an organism defined as alternative forms of a gene. A portion within Alleles the chromosome that codes for the traits/genes LAW OF INDEPENDENT ASSORTMENT Locus (loci) specific location of genes within the chromosomes Autosomal inherited on one of the 22 pairs of autosomal States that “genes for different traits are inherited separately from each chromosomes other.” genes inherited on the sex-chromosomes (X Members of one gene pair separate from one another independently of Sex-linked chromosomes) the member of other gene pairs. a gene that is when expressed whenever the allele is This allows for all possible combinations of genes to occur in the Dominant offspring. present If a homozygote that is dominant for two different characteristics is a gene that is not expressed even the allele is present. crossed with a homozygote that is recessive for both characteristics. Recessive Silent gene can only be expressed if two identical genes are present ○ The F1 generation consists of plants whose phenotype is the same as that of the dominant parent. a pair of genes in which neither is dominant over the & ○ However, when the F1 generation is crossed in the F2 generation, Codominant other. Two different genes that are inherited at the same loci on a pair of chromosomes two general classes of offspring are found. Parental type: Exact characteristics as the parental Homozygous having two identical genes for a given trait generation Heterozygous having two unidentical genes for a given trait Reciprocal type: mixture of dominant feature and recessive feature. BERNARDINO | LUCAS | MAMHOT | ORBASE WEEK 2: INTRODUCTION TO IMMUNOHEMATOLOGY IMHM311 LEC 2ND SEMESTER | A.Y.: 2024-2025 | PROF. EARL JOSEPH D. CATAMPATAN, RMT, MPH 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 INHERITANCE PATTERNS inherit the trait in a manner identical to autosomal inheritance. The sons have a 50 percent chance of inheriting the trait or not. The interpretation of pedigree analysis requires the understanding of Because the trait is dominant, the sons who inherit it will express the various standard conventions in the representation of data figures. trait. Males are always represented by squares and females by G circles. The Xga blood group system is one of the few blood group systems that A line joining a male and female indicates a mating between the two, follow an X-linked inheritance pattern. and offspring are indicated by a vertical line. A double line between a male and female indicates a consanguineous X-LINKED RECESSIVE INHERITANCE mating. A stillbirth or abortion is indicated by a small black circle. The father always expresses the trait but never passes it on to his sons. Deceased family members have a line crossed through them. The father always passes the trait to all his daughters, who are then The propositus in the pedigree is indicated by an arrow pointing to it carriers of the trait. and indicates the most interesting or important member of the pedigree. 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. 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. 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 DIFFERENT INHERITANCE PATTERNS Autosomal Recessive X-linked Dominant X-linked Recessive Autosomal Dominant BERNARDINO | LUCAS | MAMHOT | ORBASE