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Blood transfusion and haematopoietic stem cell transplantation

maisie_oj Blood Science Inglês

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History of blood transfusions
- First recroded use in 17th Century - between animals; and animals to humans
  - Unsuccessful - as many died (rejection of transfusion)
  - 1901: Blood groups first identified by Karl Landsteiner (A, B, AB, O system)
    - 1940's: Rhesus groups identified
      - Storage was a problem (due to lack of anticoagulants etc.)
        Anticoagulants and dextorse increase shelf life
        1922: First blood bank
        1946: National blood service
- Other milestones/achievements
  - Fractionation of blood
    - Clotting factors
    - Anti-D (to prevent Rhesus haemolysis in newborns)
    - Human albumin (for restoring blood volume, without adding cells)
    - Cell separators (1968)
      - Freezing blood for long term storage (in glycerol)
        Autologous blood transfusion
        Removing a patient's blood prior to surgery, then using to transfuse during blood loss)
        Useful for transfusion of rare groups
Blood groups
- 23 blood group systems
  - e.g. ABO, Rh, Kell, MNS, Duffy
    - Each is a series of antigens - determined by single gene locus or closely linked loci)
      - 400 antigens to date
- ABO system
  - Most important grouping system
  - RBCs can express either; A, B, no (O) or both (AB) antigens
    - Plasma contains naturally occuring Ab's to these antigens
      - Present without previous exposure to the blood group antigen
        Only blood grouping system to do this
        All others generate Ab's after an initial exposure
      - These Ab's are IgM (pentamer Ig units)
        Capable of activating the MAC directly
        Others (e.g. IgG) can only activate C3/4 of the complement cascade
  - Genotypes -> phenotypes
    - Genotypes
      - AA
        BB
        AB
        OO
        AO
        BO
      - Phenotypes
        A
        B
        AB (universal recipient)
        O (Universal donor)
        A
        B
        Associated natural Ab's
        Anti-B
        Anti-A
        None
        Anti-A and Anti-B
        Anti-B
        Anti-A
  - Ethnic differences
    - Caucasian (44% O; 34% A; AB = rarest)
    - Black (49% O; 19% A; 19% B; AB= rarest)
    - Oriental (43% O; 27% A; 25% B; AB = rarest)
    - Indian (22% O; 22% A; 40% B; 15% AB)
    - Australian aborigne (44% O; 56% A)
- Rh group
  - Second most important group system
  - Found in 83% caucasians (Rh(D)+)
  - Highly immunogenic
    - 1mL of RBCs will generate Ab response
      - Following an Rh(D)+ mismatched transfusion there is 90% chance of Anti-D Ab formation
        Rh(D) not the only antigen - 45 Rh antigens known (commonest = D, C, c, E and e)
Blood groups = RBC antigens
- Maybe expressed soley on RBCs (e.g. Rh)
- Or shared between RBCs and tissue (e.g. MNS)
- Some are protein alone (e.g. Rh)
- Some are glycoproteins (e.g. ABO)
  - Sugar moiety which determines A, B, or O group (modification determined by allele expressed)
- Lacking an antigen may be beneficial sometimes
  - Duffy blood group (Fy)
    - Glycoproteins Fy(a) and Fy(b)
      - Cell receptor acts as malarial entry receptor
    - Duffy negative individuals are protected from malaria
- Function of blood groups
  - Convinient in transfusion - aids selection of appropriate blood
  - But, they are functional proteins
    - e.g. Band 3 protein forms; Diego and Wr
      - Form an RBC anion channel protein (transport Cl(-) and HCO3(-)
    - e.g. Rh proteins control RBC lipid asymmetry
Antibodies and their relevance to transfusion
- Immunoglobins (Ig's)
  - IgG, IgA, IgM, IgE, IgD
    - IgM's are a large molecule (x5 Ig's together in pentamer form) - activate the complement cascade better than IgG
      - IgG single Ig molecule - activates the complement cascade
        IgG can cross the placenta, whilst IgM cannot (IgG can cause foetal problems when raised against foetal Rh(D)
        Anti-D neutralising Ab's can be given (= Rhogam)
    - Ab's made by B lymphocytes
      - Alloantibodies -> Ab's against foreign molecules
        Autoantibodies -> Ab's against self molecules
        Both auto-and alloantibodies encountered in transfusion
- Ab's against blood groups (ABO)
  - People who are blood group A have anti-B Ab's
    - People who are blood group B, have anti-A Ab's
      - These Ab's are present without an initial exposure to the offending blood type
        How?
        Naturally occuring Ab's vs. immune Ab's
        Naturally occurring Ab's
        Not present at birth
        Appear by 3-6 months of life
        Where do they come from?
        Exposure to bacterial and food proteins stimulate their production
        If sterile environment -> no anti-A or anti-B Ab's produced
        Most naturally occurring Ab's are cold Ab's
        Cold Ab's
        Warm Ab's
        Immune Ab's are warm
        Produced in response to sensitisation to blood group antigen
        Work at body temperature (37*C)
        Potentially dangerous
        Subtle RBC destruction by the reticuloendothelial system (RES), spleen etc.
        Extravascular haemolysis
        E.g. Anti-D in rhesus disease (aka haemolytic disease of newborn)
        E.g. mismatched transfusion
        All IgG Ab's
        Usually IgM
        Work better at 0-4*C (many don't work at 37*C)
        Most naturally occuring Ab's are cold Ab's
        BUT.... anti-A and anti-B have a wider thermal range and are active at 37*C
        Cause (when mismated transfusion)
        Activation of the complement cascade
        RBC lysis
        Dramatic intravascular haemolysis
        Ab's that are not activated >30*C are of no clinical significance
        Immune Ab's
        Are warm Ab's
        ->
Blood collection and processing
- UK blood source
  - Homologous blood (from donors)
    - Aged 17-70yrs
    - Max = 2 donors per year
  - Standar interview with tick box questionaire to determine fitness
    - Ask about transfusion-transmitted diseases (HIV, HBV etc.)
  - Copper sulfate test (drop of blood -> tests for anaemia)
- The blood itself
  - 450mL of whole blood collected into 63mL anticoagulant
  - Sterile, closed system
  - RBCs, plasma and platelets separated (by centrifugation)
  - WBCs removed (leukodepletion)
  - Labelled
  - ABO and Rh groups checked
  - Shelf-life = 5 weeks
- Processing
  - Whole blood
    - Cellular components
      - RBCs, WBCs and platelets
    - Plasma
      - Plamsa for clinical use
        Fresh frozen plasma
        Cryoprecipitate / cryroprecipitate depleted plasma
        Single donor plasma
      - Fractionation for plasma products
        Clotting factors (VIII and IX)
        Ig's (specific and non-specific)
Compatability testing
- Ag test
  - Direct Ag test
    - Detects Ab's bound to RBCs
      - Wash patients RBCs (from a collection)
        Add anti-human globulin (Ab against human Ab)
        Watch for agglutination (Anti-human Ab binds to Ab's on RBCs and causes aggregation)
        Positive in: Haemolytic disease of the newborn; autoimmune haemolytic anaemia and haemolytic transfusion reaction
  - Indirect Ag test
    - Detects Ab's in patients serum
      - Test (control) RBCs are incubated in patient's serum
        Anti-human globulin added
        Watch for agglutination of test cells
        Detects anti-RBC Ag's in patient's serum
        Positive in: alloantibodies in patient's serum
        Important because it excludes incompatibility

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Descrição: Blood Science Mapa Mental sobre Blood transfusion and haematopoietic stem cell transplantation, criado por maisie_oj em 01-05-2013.
Criado por: maisie_oj
Visualizações: 138
Tags: blood science
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Blood transfusion and haematopoietic stem cell transplantation

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