PPOM 1 Week 17 LEC 144-156 WORK IN PROGRESS

(144) Blood is __% plasma that includes proteins (antigens), electrolytes and antibodies

60

(144) Blood is __% formed elements (ex., cells, platelets), mostly red blood cells (RBCs), and white blood cells (wbcs, leukocytes) which have antigens

40

(144) Blood Groups

Identifying characteristic, determined by surface antigens of RBCs and other blood components

(144) Hemolysis

Life threatening blood transfusion reaction; complications include shock, acute renal failure, and DIC; Rarely anaphylaxis that ranges from urticaria to shock

(144) Immune Antibodies

Antibodies made after direct exposure to foreign antigen (like through transfusion, pregnancy, infection). Most are warm reacting antibodies (IgG that bind antigen best at 37°C – body temp.). Require use of anti-human globulin (Coombs reagent) for detection.

(144) Natural Antibodies

Antibodies made without direct exposure to the antigen (environmental exposure like bacteria or pollen stimulates them indirectly). In people never exposed to RBC antigens by transfusion, injection or pregnancy. Most are cold reacting antibodies (IgM cold agglutinins that bind antigen best below body temp. - at room temperature or lower). Activate complement

(144) Examples of Immune Antibodies

Anti-Rh, -Kell, -Duffy, -Kidd; all targeted by IgG.

(144) Examples of Natural Antibodies

ABO antibodies (Anti-A, Anti-B); all targeted by IgM.

(144) Properties of IgM Antibody Class

Large, 10 binding sites, causes agglutination + complement activation

(144) Properties of IgG Antibody Class

Smaller, crosses placenta, causes delayed hemolytic reactions

(144) ABO Blood Group antigens

Consists of Carbohydrate antigens targeted by Natural antibodies (IgM); determined indirectly by enzymes

(144) Rh (D antigens)

Consists of Protein antigens targeted by Acquired/Immune antibodies (IgG); direct gene products

(144) immediate intravascular hemolysis

Medical condition that is a result of ABO Blood Group incompatibility; result in most severe reactions

(144) Hemolytic Disease of the Fetus/Newborn (HDFN)

Medical condition that is a result of Rh (D antigen) Group incompatibility

(144) Function of Glycosyltransferases

add sugars to a basic precursor substance oligosaccharide chain called paragloboside

(144) Function of H gene

leads to production of α-2-L-fucosyl transferase that transfers a terminal fucose to paragloboside chain

(144) O gene

amorph that does not produce active enzyme so H substance remains unmodified; unmodified H precursor, without A or B antigens

(144) Forward grouping

Detects ABO antigens on RBCs by adding Anti-A and Anti-B reagents to patient RBCs, which are cold reactive

(144) Reverse grouping

Detects ABO antibodies in plasma by mixing patient plasma with known A and B cells

(144) DAT (Direct Antiglobulin Test)

Detects In-vivo coating of RBCs with IgG/complement; Detects HDFN, autoimmune hemolysis, transfusion reactions.

(144) IAT (Indirect Antiglobulin Test)

Detects In-vitro binding of patient's antibodies to reagent RBCs; Used in Type & Screen, Crossmatch

(144) Agglutinins

antibodies that cause agglutination

(144) Bombay phenotype

Only Blood phenotype that lacks H antigens; rare

(144) Blood type O

Most common blood phenotype worldwide

(144) H substance (from H gene)

Gene product that must be made first to allow A or B antigens to be attached

(144) Purpose of whole blood

predominantly used to make blood components

(144) Purpose of Packed RBCs transfusion

Increase oxygen carrying capacity; Indicated for Acute blood loss, severe anemia

(144) Purpose of Platelet transfusion

Stop microvascular bleeding; indicated for count <10k (no bleed), <50k (with bleed), <100k (CNS surgery)

(144) Purpose of Plasma (FFP) transfusion

Replace clotting factors; Indicated for Liver disease, DIC, warfarin reversal

(144) Purpose of Cryoprecipitate transfusion

Fibrinogen, Factor VIII, vWF source; Indicated for Hypofibrinogenemia, von Willebrand disease if no concentrate

(144) Purpose of Albumin transfusion

Maintain oncotic pressure; Indicated for Nephrotic syndrome, plasmapheresis, paracentesis

(144) Purpose of IVIG transfusion

Immune modulation; Indicated for Immunodeficiencies, autoimmune diseases

(144) Purpose of Factor Concentrates transfusion

Specific factor deficiencies; Indicated for Hemophilia A/B, von Willebrand disease

(144) Massive Transfusion Protocol (MTP)

replacement of >1 blood volume in 24h or >10 units PRBCs or > 4 units pRBCs in 1h with ongoing bleeding

(144) Type & Screen (T&S)

Perioperative Practice preferred over crossmatch to reserve blood inventory

(144) Immediate Spin Crossmatch

Crossmatch Testing that is quick check for ABO incompatibility (~15 minutes)

(144) Full Crossmatch

Crossmatch Testing that includes incubation at 37°C to detect non-ABO antibodies (~1 hour)

(144) Leukoreduction

Removes white cells to prevent febrile reactions, CMV transmission, HLA alloimmunization

(144) Irradiation

Prevents Transfusion-Associated Graft vs Host Disease (TA-GVHD) by inactivating T-lymphocytes

(144) Washing

Removes plasma proteins to prevent severe allergic reactions

(144) Freezing

Preserves rare blood types for up to 10 years

(144) Alternatives to Transfusions

Iron, folate, vitamin B12 supplementation, Erythropoietin (Epogen, Darbepoietin), Cell savers during surgery

(144) How Acute Hemolytic Transfusion Reactions (AHTR) occur:

ABO incompatibility, less often Kidd/Rh/Kell

(144) How Acute Delayed Hemolytic Transfusion Reactions (DHTR) occur:

Alloantibodies (Rh, Kidd)

(144) How Febrile Non-Hemolytic Transfusion Reactions (FNHTR) occur:

Cytokines, anti-leukocyte antibodies

(144) How Allergic/Anaphylactic Transfusion Reactions occur:

IgE-mediated reaction to donor proteins

(144) How Transfusion-associated circulatory overload (TACO) Reactions occur:

volume issue (fluid overload)

(144) How Transfusion-related acute lung injury (TRALI) Reactions occur:

immune issue (donor anti-leukocyte antibodies activate neutrophils)

(144) How Septic Transfusion Reactions occur:

Bacterial contamination (Yersinia, Pseudomonas, Staph); happen more with platelets (because they're stored at room temp)

(144) How TA-GVHD Reactions occur:

Donor T-cells attack recipient tissues

(144) How Acute Hemolytic Transfusion Reactions (AHTR) are evaluated:

DAT, hemoglobinuria, ↑LDH, ↓haptoglobin

(144) How Delayed Hemolytic Transfusion Reactions (DHTR) are evaluated:

Positive DAT, ↓Hgb days later

(144) How Febrile Non-Hemolytic Transfusion Reactions (FNHTR) are evaluated:

Clinical (fever, chills)

(144) How Allergic/Anaphylactic Transfusion Reactions are evaluated:

Rash, bronchospasm, anaphylaxis

(144) How Transfusion-associated circulatory overload (TACO) Reactions are evaluated:

Pulmonary edema, HTN, dyspnea

(144) How Transfusion-related acute lung injury (TRALI) Reactions are evaluated:

Pulmonary edema, no overload

(144) How Septic Transfusion Reactions are evaluated:

Fever, hypotension

(144) How TA-GVHD Reactions are evaluated:

Pancytopenia, rash

(144) How Acute Hemolytic Transfusion Reactions (AHTR) are treated:

Stop transfusion, support BP/airway, labs

(144) How Delayed Hemolytic Transfusion Reactions (DHTR) are treated:

Supportive

(144) How Febrile Non-Hemolytic Transfusion Reactions (FNHTR) are treated:

Antipyretics, stop transfusion

(144) How Allergic/Anaphylactic Transfusion Reactions are treated:

Diphenhydramine, Epi if severe

(144) How Transfusion-associated circulatory overload (TACO) Reactions are treated:

Oxygen, diuretics, slow transfusions

(144) How Transfusion-related acute lung injury (TRALI) Reactions are treated:

Supportive: O2, IV fluids

(144) How Septic Transfusion Reactions are treated:

Stop transfusion, blood cultures, antibiotics

(144) How TA-GVHD Reactions are treated:

Prevent with irradiation; supportive care if occurs

(144) Donor Screening Tests for Hepatitis B

HBsAg, Anti-HBc, HBV DNA

(144) Donor Screening Tests for Hepatitis C

Anti-HCV, HCV RNA

(144) Donor Screening Tests for HIV

Anti-HIV 1/2, HIV RNA

(144) Donor Screening Tests for HTLV I/II

Anti-HTLV

(144) Donor Screening Tests for Syphilis

RPR/IgG

(144) Donor Screening Tests for Chagas Disease (T. cruzi)

IgG Anti-T. cruzi

(144) Donor Screening Tests for Babesia

Babesia antibody

(144) Donor Screening Tests for West Nile Virus

WNV RNA

(144) Donor Screening Tests for Zika Virus

Zika RNA

(144) Blood Donor Requirements

17 years old (some states 16), 110+ lbs, No recent infection, travel to endemic areas, risky behaviors, No donation within past 56 days

(145) T lymphocyte antigen receptors (AKA T-cell receptor or TCR)

Surface proteins possessed by each T lymphocyte, highly specific for only one particular antigen

(145) Structure of T lymphocyte antigen receptors (AKA T-cell receptor or TCR)

consists of a protein dimer that possesses a variable region that binds to antigen, a constant region and a transmembrane portion

(145) Function of T lymphocyte antigen receptors (AKA T-cell receptor or TCR)

to specifically activate only those T cells that are capable of binding a particular antigen on their surface; this initiates adaptive immunological responses by antigen-specific CD8+ T and CD4+ T cells

(145) Antigen binding portion of the TCR

variable region analogous to the variable region of immunoglobulins, recognizes and binds only to peptide antigens derived from a pathogen’s proteins or self-proteins that have been complexed with MHC molecules

(145) Major Histocompatibility Complex (MHC)

genes that encode MHC molecules (HLAs), found on chromosome number 6 in a region

(145) Human Leukocyte Antigens (HLA)

molecules encoded by the MHC genes which are versions of MHC molecules; Dominant Genetic Factor Affecting Susceptibility to Autoimmune Disease

(145) Structure of MHC Genes

very polymorphic; differences between the MHC genes of donors and recipients are the major cause of tissue incompatibility and transplant rejection.

(145) Function of immunoglobulins of B cells

can recognize many different kinds of macromolecules and their fragments including, proteins, lipids and carbohydrates

(145) Step 1: Antigen Processing and Presentation by dendritic cells

Dendritic cell takes up pathogen for degradation

(145) Step 2: Antigen Processing and Presentation by dendritic cells

Pathogen is taken apart inside the dendritic cell

(145) Step 3: Antigen Processing and Presentation by dendritic cells

Pathogen proteins are unfolded and cut into small pieces

(145) Step 4: Antigen Processing and Presentation by dendritic cells

Peptides bind to MHC molecules and the complexes go to the cell surface

(145) Step 5: Antigen Processing and Presentation by dendritic cells

T-cell receptors bind to peptide: MHC complexes on dendritic cell surface

(145) Function of MHC class I molecules

present peptide antigens derived from self-proteins or from intracellular pathogens to CD8 T cells also known as cytotoxic T cells; usually do not evoke an immune response because of tolerance

(145) Function of Cytotoxic T cells (CD8 T cells)

limit the spread of intracellular pathogens by killing the infected cells that display foreign antigens

(145) Function of Helper T cells (CD4 T cells)

defend against extracellular pathogens by enhancing the phagocytosis of extracellular pathogens by macrophages and by stimulating B cells to make antibodies

(145) Function of MHC class II molecules

(on antigen presenting cells) present peptide antigens from extracellular pathogens to CD4 T cells also known as helper T cells

(145) interleukin-12

a cytokine which promotes the differentiation of T cells from naïve CD4+ T cell pools

(145) interferon-gamma

a cytokine which promotes macrophage phagocytosis of the pathogen

(145) Proteasomes

large barrel-shaped protein complexes that degrade Proteins in the cytosol that are destined for disposal, such as those that are damaged, poorly folded, or no longer needed

(145) Transporter associated with Antigen Processing (TAP)

A specialized protein present in cells that specifically transports degraded peptides across the endoplasmic reticulum membrane where they can associate with the newly synthesized MHC class I molecules.

(145) Bare Lymphocyte Syndrome

rare version of a genetic disease in which the TAP protein is nonfunctional resulting in a lack of peptide translocation into the endoplasmic reticulum

(145) Autoimmunity

A breakdown or defect in the mechanisms of tolerance; self reactive CD8 T cells respond to (become activated by) self peptides displayed on MHC class I molecules on the surfaces of normal cells

(145) Structure of MHC Class I Molecules

membrane glycoproteins found on all nucleated cells in the human body; dimer made up of an alpha chain which is non-covalently complexed with a second protein called beta-2 microglobulin