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332 Cards in this Set
- Front
- Back
which products are leukoreduced
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whole blood, platelets, rbss
|
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what does leukoreduction mean
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reducing the majority of wbcs from blood products
|
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what are the deleterious effects of wbcs in blood
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1. wbcs deteriorate while sitting in bag leading to cytokine release and febrile transfusion reactions (esp in plts)
2. wbcs present foreign HLA antigens to host 3. some viruses live in wbcs |
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why do we care about the production of HLA antibodies from a transfusion reaction
|
- causes future problems:
with platelet refractoriness future febrile reactions issues with transplants |
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what HLA antigen class is the big problem on wbcs in transfusions
|
HLA II on wbcs presents to HLA1 to form anti-HLA1 antibodies (on plts) or anti plt ab
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what viruses can live in wbcs (thus increasing risk of transfusing virus if no leukoreduction)
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CMV
HTLV1 and 2 EBV |
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what are some of the ways we leukoreduce
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filters on dialysis/apheresis machines
separate by centrifugation to isolate desired product |
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when should one leukoreduce
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ideally before 5 days
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indications for leukoreduction
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-prevent febrile reactions in those with hx
- prevent HLA immunization for those getting plts with heme malignancies - prevent CMV in immunocomprised recipients |
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weird complication from leukoreduction
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some patients on ACE inhibitors can get hypotension with leukoreduced products
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is leukocyte reduction the same as irradiation
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no
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which is better to prevent GVHD leukocyte reduction or irradiation
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irradiation virtually eliminates risk for GVHD; LR only reduces risk
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can granulocytes be irradiated
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yes, but not leukoreduced
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which filters better (for leukoreduction) cold or room temp rbcs
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cold rbcs are better for filtering
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in what patients are you most likely to get filter failures in terms of leukoreducing
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sickle cell patients
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only indication for irradiated blood products
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to eliminate transfusion associated GVHD
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what organs are most affected by transfusion associated GVHD
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skin, liver, GI tract, mucosal membranes and bone marrow
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clinical course of transfusion associated GVHD
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rapid, can be fatal within 1 month from overwhelming infection
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1 clinical manifestation of transfusion associated GVHD
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rash on palms and soles
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what does bone marrow look like in transfusion associated GVHD
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hypocellular and fibrotic
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when does transfusion associated GVHD reaction occur
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2-30 days (usually 10 or so); delayed febrile
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what cell type in the product causes transfusion associated GVHD
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donor T lymphocytes (CD4, CD8 and NK)
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can transfusion associated GVHD occur in an immunocompetent recipient and if so, how
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one way HLA match:
donor shares HLA with half of recipients tissue. Donor's T cells target the foreign half; the recipients own counter-attack T cells only see self-HLA and don't counterattack |
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common sources of irradiation
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gamma irradiators
xray irradiators linear accelerators (used for radiation therapy |
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how much irradiation to give
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25 Gray to center of bag; 50 Gray max, 15 gray min (at periphery)
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indications for treatment with irradiated blood products (8)
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T cell defects (acquired/congenital)
intrauterine pregnancies/premies HLA matched products, family member donors hematopoietic stem cell transplants those with Hodgkins (and other heme malign) - some solid (like neuroblastoma) if on fludarabine fresh whole blood cardiac patients |
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what products are always irradiated
|
granulocytes
|
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who doesn't need to be irradiated
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solid organ transplant patients (even though being treated)
HIV small volume transfusions to neonates if previously frozen |
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disadvantages of irradiating
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K goes up, hgb goes up (maybe wash for neonates)
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how long can you store irradiated products
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28 days
|
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which moms need prophylactic RhIG
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D neg moms (they can form anti D's if a D+ fetus)
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what is the risk that a D- mom can form antibodies with the first pregnancy
|
20% (occurs at delivery); standard is to give one vial at 28 weeks (risk goes from 16% to 1%) and then after (within 72 hours ideally)
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what is a "vial" of rhogam
|
one standard dose of antiD antibodies (300ug or 1500 IU) sufficient to protect against 30 ml of D+ blood (or 15 ml rbcs)
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so, do you give one vial post delivery or more than one
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based on fetal bleed screen (if neg - just one vial; if pos, do a quantitative test to determine how much to give)
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how doesa fetal bleed screen work
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put rbcs (baby and mom) on a slide, add anti D, add indicator to agglutinate and form rosettes against those bound with anti D; count rosettes
positive test: 3 or more/10 hpf |
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methods for a quantitative test to determine how much rhogam is needed for maternal-fetal bleed in a D- mom
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- Kleihaur-Betke
- flow |
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how does the Kleihaur-Betke method work and how from there can you determine how much rhogam to give
|
HgF is acid resistant, HgA is not; flood blood smear with acid; count 2000 cells, percent that are "bright" is the percent of fetal cells; multiple that percent by 5000 ml (presumed mom blood volume) and get amount of fetal blood mom was exposed to - divide that by 30 ml (for one vial of rhogam) and that will give you how many vials to give with the addition of a "safety factor" (rounding up) (fudge factor is if fraction is <0.5 round up one vial, if .5 to .9 round up two vials) e.g. 2.2 give 3 vials but if 2.5 give 4 vials
|
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if get weight instead of assuming blood volume, how would you calculate it
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weight (in Kg) * 70
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what should make you think of a transfusion reaction (6)
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fever/chills, circulatory/pulmonary issues, "doom", skin changes, pain, coag/bleeding issues
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transfusion reactions that present quickly with fever (4)
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acute hemolytic, febrile non-hemolytic, transfusion-related sepsis, TRALI
|
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transfusion reactions that present delayed but with fever (2)
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delayed hemolytic, transfusion associated GVHD
|
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transfusion reactions that present quickly without fever (5)
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allergic, hypotensive, transfusion-related dyspnea, TACO, acute pain
|
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transfusion reactions the present delayed and without fever
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delayed serologic, post-transfusion purpura, iron overload
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what is meant by an "acute" transfusion reaction
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during the transfusion to the next 24 hours
|
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what is the time frame for a delayed transfusion reaction
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greater than 24 hours, can be up to weeks later
|
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what are some of the first steps in how respond to a possible transfusion reaction
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1. stop transfusion
2. perform clerical check 3. draw post transfusion sample |
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what are the three tests you would immediately perform on a post transfusion sample to work up for a possible transfusion reaction
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1. hemoglobinemia
2. DAT 3. ABO/Rh repeat testing if all negative, have ruled out acute hemolytic transfusion reaction |
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how does the test for hemoglobinemia work
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collect blood in an EDTA tube, centrifuge, if as little as 2-5 ml of hemolyzed blood, will detect that as off color in supernatant
|
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is the hemoglobinemia test sensitive, specific both or neither
|
very sensitive - not specific;
can have "positives" with bad sticks, nonimmune hemolysis and G6PD can have false negatives if delay in blood draw |
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what is a DAT test
|
direct antibody test
looking for in vivo coating of antibodies/complement on rbcs (IgG and C3d) so, have coated rbcs, add an antiIgG or anti-C3d that agglutinates the coated rbcs |
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what antibodies can classically coat an rbc without in vivo agglutination
|
IgG that is nonABO
|
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what is the first question you should ask if you get a positive DAT
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what was the pretransfusion DAT - if there was one, maybe not the problem, if there wasn't one, get busy!!
|
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if early reponse tests (DAT, ABO/rh repeat testing, and hemoglobinemia tests) show something of concern, what tests could you then consider (2nd tier testing; 6)
|
haptoglobin, bilirubin, LDH, urine hemoglobin, crossmatch, eluate
|
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what is the function of haptoglobin
|
to bind free hemoglobin (decreased when free hemoglobin is running around - aka acute hemolytic transfusion reaction)
|
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what happens to bilirubin (conjugated or unconjugated) in acute hemolytic transfusion reactions
|
they go up fast (as breakdown product of hemoglobin) but also go down fast -
historically, thought indirect (unconjugated) was intravascular and direct (conjugated) was extravascular |
|
which is the possible sign of a transfusion reaction: hematuria or hemaglobinuria
|
hemaglobinuria
|
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on a peripheral smear, what would you see in an intravascular hemolytic reaction
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schistocytes (classic example ABO incompatibility)
|
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on a peripheral smear, what would you see in an extravascular hemolytic reaction
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spherocytes (classic example IgG that bind rbcs but don't fix complement)
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what would you do if you specifically suspected a septic trx reaction (ex. high fever >102 or severe rigors)
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culture everything :)
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what would you do if you specifically suspected a respiratory type trx reaction
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CXR, BNP (to rule out affect of circulatory overload)
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what would you do if you specifically suspected an allergic type trx reaction
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if severe only, consider IgA
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most common cause of acute hemolytic transfusion reactions and frequency
|
clerical errors (60%)
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|
most sensitive clinical symptom of an acute hemolytic transfusion reaction
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fever/chills (80% present with this alone) - time frame - a lot within first 15 minutes; peak of curve (representing distribution of those getting fever) is at 70 minutes - btw, this is why you are to transfuse slowly
|
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how long before hemoglobulinemia due to acute hemolytic transfusion reactions goes away
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matter of hours
|
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how long before hemoglobulinuria due to acute hemolytic transfusion reactions goes away
|
gone in a day
|
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what could result in a false negative DAT in an acute hemolytic transfusion reaction
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wait too long before do DAT, the offending rbcs are destroyed
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name two useful tests to rule in DIC
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d-dimers, fibrin split products
|
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which antibody type fixes complement better IgM or IgG
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IgM
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name some of the chemokines/cytokines released during an acute hemolytic transfusion reactions
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C3a/C5a
TNFalpha (fever producing) IL1b (fp), IL6 (f) and IL8 bradykinin |
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how does an acute hemolytic transfusion reaction affect coagulation/cause DIC (3)
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Ag-Ab complexes trigger Factor X11 down intrinsic pathway
cytokines/TNF triggers TF down extrinsic pathway also fibrinolysis is triggered too |
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vasodilation in an acute hemolytic transfusion reaction is caused by what (2)
|
nitric oxide
bradykinin |
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renal damage in an acute hemolytic transfusion reaction is caused by what (2)
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- renal vasoconstriction (compensating for systemic hypotension)
- microthrombi leads to ATN |
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what is a febrile nonhemolytic transfusion reaction
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UNEXPLAINED 1C (2F) elevation of temperature, diagnosis by exclusion
caused by: wbc-derived cytokines (ex. TNFa, IL1a, IL6) or plt-derived sCD40L |
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where do most febrile nonhemolytic transfusion reactions occur
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often in PLT products (which contain plts and unhappy wbcs)- so cytokines, etc in bag that is given to recipient
If from rbcs, usu. recipient Ab or wbcs cause problem against wbcs in donor |
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if very early fever in transfusion reaction, what should you think of
|
septic
|
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what will prevent a febrile nonhemolytic transfusion reaction
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prestorage leukoreduction (esp needed as prestorage in plt products)
|
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what is the number one infectious risk from transfusions
|
transfusion-related sepsis
|
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what products (plts vs rbcs) have what kind of bugs
|
plts - skin contaminants (gram positive cocci) and rarely gram neg rods (those cause fatalities)
rbcs - skin contaminants (staph epidermidis) - Gram neg rods (yersinia, e coli, enterobacter, serratia, pseudomonas) - YEEPS! subclinical sepsis in donor |
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what do yersinia, e coli, enterobacter, serratia, pseudomonas have in common
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like cold temps, like iron-rich environment; also capable of releasing endotoxins
|
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number one infectious cause of FATALITIES in transfusion reactions
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babesia (protozoan parasite)
|
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what is the "endotoxin effect" in a transfusion-related septic event
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rapid onset of super high fever, rigors, shock, dic
abdominal complaints |
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what are the three causes of an acute crash in a transfusion
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-sepsis
- anaphylaxis (really rare) - acute hemolytic reaction |
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what color does a bacterial contaminated blood unit turn
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darker/purple
|
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if going to culture to evaluate for a bacterial contaminated blood unit, where do you get the source material
|
from the bag (not from the segments outside the bag)
|
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do leukoreduction filters have any affect in filtering out bacterial contamination in a blood unit
|
actually, yes, shown with Yersinia
|
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what's the shelf-life for plts
|
5 days
|
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**most common cause of transfusion related fatality
|
TRALI
|
|
blood product specific source of TRALI
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historically thought of as a FFP issue, but can happen in any type of blood product
|
|
define TRALI
|
new acute lung injury (ALI) less than 6 hours after transfusion
and no other known risk factors for pulmonary edema |
|
define ALI (in context of TRALI)
|
hypoxemia (o2 sat<90% as one measure) and bilateral CXR infiltrates
|
|
symptom sequence for TRALI
|
fever (not as fast as septic but generally sooner than febrile, nonhemolytic) chills, Hypertension followed by hypotension
|
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name two mechanisms to get TRALI
|
1. donor antibody mediated (donor antibody - HLA or neutrophil antibodies - attacks PMNs, lead to pulmonary endothelial damage in part through ROS)
2. two event pathway - preexisting condition in recipient followed by biologic response modifiers (sCD40L) or Ab that promote damage |
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which donors are most likely to cause TRALI
|
donors who have been transfused or pregnant
|
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percent fatalities and percent recovery from TRALI
|
fatalaties 5-25%
recovery 80% |
|
allergic transfusion reactions are mediated by what Ig subtype
|
IgE
|
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only transfusion reaction in which you might consider restarting the transfusion
|
mild allergic reaction (if hives/angioedema clears with benadryl/treatment)
|
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what clinical sx is almost always present in allergic reactions from transfusions
|
skin findings
|
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which antibody is pentameric
|
IgM
|
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which antibody is classically a dimer
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IgG
|
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which antibody has two dimers coupled by a secretory molecule
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IgA
|
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what underlying problem should you think of when you hear about severe allergic reactions in the setting of transfusion reactions
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though not frequent, think of IgA deficiency - patients with IgA deficiencies can develop an IgE-mediated anti IgA, which when transfused can have a reaction to the IgA in the donor blood
|
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when you test for antiIgA in the lab what are you testing for
|
you are looking for an IgG anti IgA not an IgE anti IgA
|
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a relatively common cause of allergic reactions in transfusion reactions in Asians
|
haptoglobin deficiency
|
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how to rule out IgA deficiency as a cause of allergic reaction in transfusion reaction
|
on pretransfusion sample, do an IgA level; if super low, then do an antiIgA
|
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what can you do if you determine IgA deficiency as the cause of allergic transfusion reaction
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use IgA deficient donors; wash rbcs (and to a lesser extent) plts
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cause of acute hypotensive transfusion reaction
|
bradykinin (from those on ACE inhibitors or from some LR filters)
|
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what is transfusion associated dyspnea
|
diagnosis of exclusion (ie not TRALI, TACO or allergy)
|
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what is TACO
|
transfusion associated circulatory overload: acute CHF due to transfusion
|
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symptoms of TACO
|
- typical CHF (JVD, dyspnea, hypertension, hypoxia)
- CXR: bibasilar infiltrates with enlarged cardiac silhoutte |
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ways to clinically distinguish between TACO vs. TRALI (5)
|
- diuretics work in TACO
- hypotension eventually in TRALI - fever in TRALI - CXR: cardiac silohoutte in TACO - BNP up in TACO |
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what is the cause of delayed hemolytic reactions
|
an anamnestic response of antibodies initially too low to detect that come flying back on exposure - most common with Kidd, Kell, Duffy
|
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where do most delayed hemolytic transfusion reactions occur
|
extravascular except kidd which can often occur intravascularly
|
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two useful lab findings in those with delayed hemolytic transfusion reactions
|
- icteric serum
- mixed field (some agglutination but not entirely on gel) DAT |
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what must be absent in delayed serologic transfusion reactions
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hemolysis
|
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clinical course for transfusion-associated GVHD
|
nearly always fatal
|
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common clinical sx for transfusion associated GVHD
|
- rash, mucositis, hepatitis, bone marrow failure
on average 7-10 days post transfusion |
|
prevention of transfusion associated GVHD
|
irradiation (so esp important in those immunosuppressed/leukopenic)
|
|
should frozen blood products receive irradiation (if clinically indicated)
|
usu not cuz the freezing process kills the wbcs in the bag, except if cryopreserved (in glycerol) where usually the wbcs persist
|
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maximum number of days post irradiation for a blood product
|
28 days (or regular expiration date - whichever first)
|
|
presentation of post-transfusion purpura
|
severe thrombocytopenia (<10K) and wet purpura (oozing from mucosal surfaces)
|
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what is post-transfusion purpura
|
antibody mediated destruction of platelets ~ 10 days post transfusion
|
|
mortality rates for post-transfusion purpura
|
up to 12%, intracranial bleeds
|
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who gets post-transfusion purpura
|
females 5:1 males; mostly multips - patients who lack HPA-1a are the most common to get this
|
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why does post-transfusion purpura occur
|
most commonly recipient has previously developed an HPA-1A antibody that then targets the transfused plt with that antigen and strangely this goes on to target their own plts as well (hence why such severe thrombocytopenia)
|
|
treatment for post-transfusion purpura
|
ivig or if failure plasma exchange
|
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what are the three phases of test tube testing for agglutination
|
1. immediate spin (serum + rbcs together in tube, centrifuge for 15 second, examine)
2. 37 C (serum+rbcs inclubate at 37C) length of time dependent (LISS, PEG/alb or none) 3. IAT (above, wash, add AHG, cenrifuge and examine) |
|
list times for 37C test tube agglutination study depending on presence or absence of potentiators present
|
LISS- 10-15 min
alb/PEG 15-30 min none 30-60 min |
|
what does IAT look for
|
ability of antibodies (in vitro) to identify ags on rbcs. use AHG to agglutinate since many ab (e.g. IgG) won't efficiently agglutinate rbcs
|
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what does DAT look for
|
presence of antbodies in vivo that recognized ags on rbcs. Use AHG to help agglutinate since many ab (eg IgG) won't efficiently agglutinate rbcs
|
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where does dosage matter most
|
Kidd, duffy, Rh and MNS systems
|
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why are ficin and papain useful in blood group testing
|
they can enhance, decrease or not affect ab-ag binding - thus enabling us to classify the different types of ags on rbcs
|
|
what are the four members of the ABO family
|
ABO blood group, Lewis, I/i, P blood groups
|
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what are the three blood groups/blood group families that are enhanced by enzymes
|
1. abo family (includes abo, lewis, I/i and P)
2. Rh 3. Kidd |
|
what are the three blood groups that are decreased by enzymes
|
1. MNS
2. Duffy 3. Lutheran |
|
what are the three blood groups that are not affected by enzymes
|
1. Kell
2. Diego 3. Colton |
|
what are neutralizing substances in study of agglutination in blood bank
|
premix with neutralizing substances reducing the strength of the antibody (blocks binding sites) to lessen ab-ag reaction
|
|
neutralizing substance for ABo family
|
saliva (secretor)
|
|
neutralizing substance for lewis
|
saliva (secretor for Leb)
|
|
neutralizing substance for P1
|
hydatid cyst fluid, pigeon egg fluid
|
|
neutralizing substance for Sda
|
urine
|
|
neutralizing substance for chido, rodgers
|
serum
|
|
what are lectins and what are their utility
|
seed derived products that act like antibodies (and can be very specific); useful in polyagglutination studies
|
|
specificity of lectin: dolichos biflorus
|
A1
|
|
specificity of lectin: Ulex europaeus
|
H
|
|
specificity of lectin: vicia graminea
|
N
|
|
specificity of lectin: arachis hypogea
|
T
|
|
specificity of lectin: glycine max
|
T, Tn
|
|
specificity of lectin: salvia
|
Tn
|
|
what is the definition of a blood group antigen
|
present on rbcs and targeted by an alloantibody
|
|
fx of warm reactive antibodies (4)
|
1. often IgG
2. require exposure 3. cause HTR, HDN 4. significant clinically |
|
fx of cold reactive antibodies (4)
|
1. often IgM
2. naturally occurring 3. don't usually cause HTR/HDN 4. usually not significant clinically |
|
is ABO a cold reactive or warm reactive ab
|
interestingly, best as cold reactive and a lot of ABO is IgM but obviously very clinically significant
|
|
describe a type 1 chain in the ABO system
|
one of two chains upon which the H antigen can be built: composed of a
Gal----GalNAc-----R (bound by beta1-3) between gal-galnac; R group is predominantly glycoprotein, in secretions |
|
describe a type 2 chain in the ABO system
|
one of two chains upon which the H antigen can be built: composed of a
Gal----GalNAc-----R (bound by beta1-4) between gal-galnac; R group is predominantly glycolipids, on rbcs |
|
what is a secretor
|
80% of us: we have the Se gene (encodes for FUT2); someone who can make H antigen on type I chains
|
|
what does FUT2 do
|
makes H antigen: FUT2 adds a fucose to the terminal gal in TYPE I chains (chains that are mostly in secretions)
|
|
what does the H gene encode
|
the H gene encodes FUT1
|
|
what does FUT1 do
|
makes H antigen on TYPE 2 chains by adding fucose to terminal gal (recall type 2 chains are found predominantly on rbcs)
|
|
what does the A gene encode for
|
GalNAc transferase; adds a galNAc to terminal gal on H antigen, making A antigen
|
|
what does the B gene encode for
|
gal transferase; adds a gal to terminal gal on H antigen- making B antigen
|
|
what chains do the gene products of A and B genes operateon
|
both type 1 and type 2
|
|
order the following ags based of amount of H antigen expressed:
O, B, A1, A2, A2B, A1B |
O>A2B>B>A2B>A1>A1B
|
|
Where are the A, B, O genes and what does O gene do
|
czome 9; O gene does nothing
|
|
when do ABO antigens appear in newborn
|
6 weeks
|
|
when do ABO antigens achieve adult levels
|
4 years
|
|
when do ABO antibodies appear
|
4 months
|
|
when do ABO antibodies reach adult levels
|
10 years
|
|
what type antibodies are anti A and anti B
|
IgM (hence don't cross placenta)
|
|
what type of antibodies can a blood group O person have that is different from type A and type B people
|
it is thought that blood group O people develop anti A and anti B antibodies that are IgG
In addition, a unique anti-AB are formed that are IgG these all can cross placenta and cause problems in utero |
|
order of A, B, O and AB blood types across all races
|
O>A>B>AB
|
|
will ulex europeaus only react against O blood type
|
no, it's reacting to the H antigen. Thus, A1B will react less than A2
|
|
what is the most common cause of HDFN
|
blood type O mom with IgG antibodies against baby with A, B or AB; mild form
|
|
what blood group antigens does a type A individual have
|
A, H
|
|
which is more frequent A1 or A2
|
A1 (80%); A2 (20%)
|
|
which has more A antigen on its surface A1 or A2
|
A1 has 5x more than A2
|
|
what is important about distinguishing between A1 and A2
|
1. understand relative amount of H/strength of A expression
2. slight biochemical differences in the A2 strand 3. some of A2 population (esp A2B) can form AntiA1 ab |
|
who is the universal recipient and why
|
AB, no antibodies to A, B or H
|
|
what is forward grouping and what's another name
|
cell testing; patients rbc against lab's antibodies
|
|
what is reverse grouping and what's another name (2)
|
backtyping/serum testing; patients serum agains lab's rbcs
|
|
what is an acquired B phenotype
|
look like reacting to AntiB on forward testing (wk reaction with B) but no obvious B expression of reverse testing
|
|
what population can acquired B phenotype happen in
|
A1 individuals
|
|
how does acquired B phenotype develop
|
gram neg bugs (from sepsis, colon ca, obstruction) come into contact with A antigen and chew off an Acetyl group off of GalNAC to make GalN; then reagent antiB will think it's B and react
|
|
ways to resolve acquired B phenotype in lab
|
1. acidify serum
2. autoincubate (mix own antib with antib) 3. monoclonal Ab that don't recognize the acquired B |
|
what is the bombay phenotype (Oh)
|
no Se or H genes so no A, B or H antigens; strong antiA, strong AntiB and strong AntiH
|
|
what is the genotype of bombay phenotype (Oh)
|
hh,sese
|
|
lab findings for bombay phenotype
|
O forward, O reverse, screen +
|
|
what is parabombay phenotype
|
essentially same as bombay phenotype except have Se gene and thus make some H antigen in their secretions and a little in their plasma
|
|
what does the Le gene encode and what does it do
|
Le gene encodes FUT3 that adds a fucose to subterminal GalNAc on TYPE 1 CHAINS only. This make an antigen known as Le a (that is without Se gene)
|
|
if Le gene and Se gene what do you get
|
Le b: this is two fucose molecules (one on terminal gal and one on subterminal GalNAc)
|
|
what options (3) can you get if se gene and le gene act on type 1 chains
|
HLe b, ALe b, B le b
|
|
why do type I chains matter in the blood if they are generally in secretions
|
b/c free type I chains can float in plasma and adsorb onto rbcs (le b does this much better than le a - which is in low quantity anyway) so adults tend to look le a-b+
|
|
what are the three possibilities for lewis antigen expression in relative order
|
le (a-b+), le (a+b+) le (a- b-) - though infrequent the last one can have significance (>20%) of blacks
|
|
are lewis antigens significant or no
|
generally not too significant, IgM, seen mainly in Le (a-b-)
|
|
funny thing about lewis system and pregnancy
|
antigens can decrease during pregnancy and person can convert to le(a-b-)
|
|
two bugs that interact with le blood system
|
norwalk and E coli UTIs
|
|
what chain(s) does the I system work on
|
type II chains
|
|
what does anti I react to, how about anti i
|
anti I: 3D structure of branching type II chains
anti i: 3D structure of relatively simple type II chains |
|
who has "big I" antigens, who has "little i" antigen
|
big I - big people
little i - little people |
|
Auto anti I are found in what diseases (2)
|
1. mycoplasma pneumonia (esp older adults)
2. cold agglutinin disease |
|
auto anti i are found in what disease (1)
|
infectious mono
|
|
what is the antigen in the P system
|
P1 (modified by P and Pk)
|
|
most people are P1 - what does this mean
|
P+P1+Pk-
|
|
significance of antiPP1Pk (in contrast to antiP1)
|
antiPP1Pk can cause HDFN, HTRs
antiP1 - IgM, not so significant |
|
p is receptor for what bug
|
parvovirus
|
|
in what population would you see an increase in antiP1
|
bird handlers (neutralization with pigeon eggs...)
|
|
what is paroxysmal cold hemaglutinuria and what are its associations
|
biphasic IgG (donath landsteiner biphasic hemolysin) that reacts against P
associated with: syphilis, viral infections in kids |
|
what are the five antigens in the Rh system
|
D, C, E, c, e (no little d that just means not big D)
|
|
what are the two genes that dictate the rh antigen system
|
RHD and RHCE
|
|
what is little d
|
mutated or deleted D
|
|
of R1, R2, RO, Rz, r', r", r, ry, which has big D
|
R1, R2, RO, Rz,
|
|
of R1, R2, RO, Rz, r', r", r, ry, which has little D
|
r', r", r, ry,
|
|
of R1, R2, RO, Rz, r', r", r, ry, which has big C
|
R1, Rz, r', ry
|
|
of R1, R2, RO, Rz, r', r", r, ry, which has little c
|
R2, RO, r", r
|
|
of R1, R2, RO, Rz, r', r", r, ry, which has big E
|
R2, Rz, r", ry
|
|
of R1, R2, RO, Rz, r', r", r, ry, which has little e
|
R1, RO, r', r
|
|
what are the big four Rh antigens that occur in our population most often
|
R1, R2, RO and r
|
|
frequency of big four rh antigens in blacks and whites
|
whites: R1, r, R2, Ro
blacks: Ro, r, R1, R2 |
|
are rh antibodies igm or igG
|
warm requiring IgG
|
|
what is the most immunogenic nonABO antigen
|
Rh
|
|
where do HTRs occur in Rh reactions
|
extravascular, prototypical for HDFN (for antiD and antic)
|
|
why are whites usually little d
|
deletions from big D
|
|
why are blacks often little d
|
they have a pseudogene in its place
|
|
why are asians often little d
|
have big D but inactive protein product
|
|
what is a weak D phenotype
|
people in whom antibodies coat rbcs but need AHG to cause agglutination (IAT); caused by deletions,cis/trans etc; IAT required for D- donors and d- babies with d- moms (to make sure they are not actually D+ not reacting- b/c don't want to give D+ blood to D- person)
|
|
what is partial D
|
missing certain epitopes on D antigen on exterior part
|
|
how can partial D cause problems
|
if exposed to D positive blood, you may develop Ab against the portion of the D antigen that you lack
call them d- |
|
do partial D moms need Rhogam
|
yes!
|
|
in the kidd system, which antigen (of two) is more common
|
Jka>jkb (unusual)
|
|
are Kidd antibodies IgG, IgM or both
|
mostly IgG, exposure requiring but some IgM (as fix complement)
|
|
two famous things about Kidd
|
1. marked dosage effect
2. variable expression over time (cause delayed HTRs often)*** |
|
where are MNS antigens found
|
On glycoproteins named
glycophorin A glycophorin B |
|
what MNS antigens are found on glycophorin A
|
M and N (equal frequencies in population)
|
|
what MNS antigens are found on glycophorin B
|
S,s, U (find s more than S in population)
|
|
what is the difference between M and N antigens
|
the last five aa on the glycophorin A molecules (specifically the last and the fifth to last)
|
|
where is the U antigen found
|
on glycophorin B - whether S or s "universal"
|
|
what is the difference between glycophorin B molecules that are S vs. s
|
one a.a.difference between the two
|
|
what MNS pattern can you find in some small percent (2%) of blacks but not at all in whites
|
S-s-U- (they completely lack glycophorin B)
|
|
compare and contrast anti M/N antibodies within AntiS,s,U antibodies
|
antiM/N: naturally occurring, cold IgM, "insignificant", dose effect
antiS,s,U: exposure requiring, warm IgG, significant, minimal dose effect |
|
what are the two antigens for the duffy system
|
Fya, Fyb
|
|
what is the phenotype for the duffy system for 2/3rd of blacks and why
|
Fya- Fyb- they have an FyFy genotype and no duffy genes at all
|
|
what is the Duffy system antibodies: IgG or IgM
|
warm, IgG and, like Kidd in many ways (dose effect, variable expression, delayed HTRs) but lower severity than kidd
|
|
what is Duffy receptor a natural receptor for
|
P. vivax
|
|
what do those who are Fya-b- have resistance to
|
malaria from P. vivax and P. knowlesi
|
|
what are the two main ag of the lutheran system
|
Lu a and Lu b (b is high frequency)
|
|
what destroys Lu antigens
|
many enzymes and DTT
|
|
are Lutheran igG or IgM
|
mostly IgG except Lu a - despite this only mild HTRs and no HDFN
|
|
what are the two major antigens of the Kell system
|
K (K1, Kell) and k (K2) (k more frequent)
|
|
what is the second most common immunogenic antigen outside of the ABO blood group
|
Kell
|
|
what kind of antibody is K1
|
warm, exposure requiring IgG, severe HTRs, HFDN
|
|
is K1 hemolytic
|
not really; the antibody binds precursor rbcs and prevents them from forming mature rbcs
|
|
what does kell null mean and why do they matter
|
Kell antigens are missing; Kx (nearby antigen on rbcs) is increased; anti-Ku develops (u for universal) and need to have blood from other kell null individuals
|
|
what is the McLeod phenotype/syndrome
|
absence of Kx antigen, decrease in Kell antigens resulting in membrane instability with acanthocyte formation (acanthocytic hemolytic anemia)
|
|
what is the McLeod phenotype associated with
|
x linked Chronic Granulomatous disease (lack of NADPH oxidase, infection with oxidase positive organisms like Staph)
|
|
where are the Diego antigens found
|
Band 3 (HCO3/Cl exchanger)
|
|
what are the two sets of antigens in the Diego system
|
Dia/b (b high frequency)
wra/b (b high frequency) |
|
do Di a/b antibodies matter clinically
|
cause severe HDFN but not so much HTR
|
|
Do wra/wrb antibodies matter clinically
|
Wra - naturally occurring but can cause HTRS and HDFN
Wrb- common autoantibody |
|
which is higher frequency in the Colton system
|
Co a is higher (like ~100%) compared to Co b (10%)
|
|
are Colton antibodies IgG or IgM
|
mostly IgG, not common abs, can cause HDFN
|
|
what is the Dombrock system
|
composed of multiple antigens with Do a/Do b being the most common, can cause some HTRs but not HDFN (acute and delayed)
|
|
what is the Yt system
|
Cartwright (found on acetylcholinesterase in CNS but also rbcs)
Yta is very high frequency (>99%) can cause HTRs Ytb lower frequency (<10%) - usu not significant |
|
what is the Xg system
|
on x czome;
on all panels but doesn't cause problems |
|
what is Vel
|
rare ab; but anti-Vel can cause big problems, not part of system, mix of IgG and IgM; can look weak but cause big problems,
|
|
if vel negative person, do what
|
give vel neg blood
|
|
what are the two endpoints you look for in a crossmatch
|
hemolysis or agglutination
|
|
with hemolysis, what is often happening molecularly and what antibody type mediates this
|
complement is being fixed and this is often IgM mediated
|
|
classification of cold reactive antibodies (2 fx and 6 examples)
|
- often IgM
- often reacting against CHO antigens - eg. include entire ABO family (ABO, Le, I, P) and M, N |
|
classification of warm reactive antibodies (2 fx and 4 examples)
|
- IgG
-often reacting against protein antigens - e.g. Rh, K, Jk, Fy |
|
what are the two end points for evaluation of compatibility
|
agglutination, hemolysis
|
|
what are five factors that can alter antibody-antigen reactions
|
1. change temperature
2. centrifugation to overcome size differences between rbc and antibodies 3. electric issues - use LISS to minimize charge repulsion 4. alter pH (7.0 seems to optimize many reactions) 5. change relative concentrations (usually two drops serum with one drop of 2-5% rbcs but can change that) |
|
cold reactive abs usually are what type and react to what type of antigen. Name six examples of cold reactive abs in the blood group systems
|
- IgM; react to CHO antigens
examples: all of ABO family (ABO, Lewis, P and I), M and N |
|
warm reactive abs usually are what type and react to what type of antigen.
|
- IgG, react to protein antigens
examples:Rh, K, Jk and Fy |
|
what charge do rbcs tend to have and why
|
neg; due to sialic acid residues
|
|
how far can an IgG molecule reach
|
14 nm
|
|
how far can an IgM molecule reach
|
30 nm
|
|
what is the zeta potential of an rbc
|
distance rbcs stay from one another due to charge repulsion; 14 nm
|
|
why is a pH of 7.0 optimal for ab-ag interaction on rbcs
|
b/c at 7.0, rbcs have a negative charge and antibodies have a positive charge
|
|
what is the problem with too low a pH
|
dissociation of ab-ag interaction - by lowering the pH, you can actually elute the ab off the rbcs
|
|
what is the prozone effect in antibody-antigen interaction
|
too much Ab so covering rbcs and limit their ability to interact with each other (aka agglutinate)
|
|
when are potentiators added and name 4 examples of potentiators
|
after immediate spin, prior to 37C to enhance Ab-ag binding.
examples: LISS, PEG (decrease ionic cloud by moving out H2O), albumin (reduces zeta), proteolytic enzymes (last not routinely used) |
|
what is the drawback of PEG and how do you try to get around it
|
can cause nonspecific agglutination; must wash before IAT and consider not at 37C
|
|
without a potentiator how long do you incubate at 37C
|
30-60 min
|
|
with albumin, how long do you incubate at 37C
|
15-30 min
|
|
with LISS, how long do you incubate at 37C
|
10-15 min
|
|
with PEG< how long do you incubate at 37C
|
15 min...?
|
|
in test tube agglutination studies, what does a turbid background mean
|
no or little agglutination (0-1+)
|
|
in test tube agglutination studies, what does a pellet mean
|
4+ agglutination
|
|
what is in the gel for gel agglutination studies and how do they work
|
anti IgG designed to grab onto IgG-coated rbcs as they go by - the distance of how far the go in the tube is related to how coated they are (if really coated rbcs won't make it far through the tube). the negative rbcs make it to the bottoms
|
|
how does the sensitivity of gel testing compare to LISS and PEG potentiation
|
better than LISS; about the same as PEG
|
|
what is on the bottom of a solid phase testing microwell
|
lysed "donor" rbcs so that splayed across the well is rbc antigens
|
|
how does solid phase testing work
|
lysed donor rbcs/rbc antigens, patient serum (with antibodies). then add "indicator rbc bound to IgG" - like of like IAT but the AHG is replaced by AHG bound to rbc.
|
|
what does a positive look like on solid phase testing
|
carpet across well; if negative, pellet in center
|
|
which type of compatibility testing can be automated
|
gel and solid phase
|
|
in comparing Tube LISS, Tube PEG, Gel and solid phase testing, which is best known for: cold autoantibody enhancement
|
Tube LISS
|
|
in comparing Tube LISS, Tube PEG, Gel and solid phase testing, which is best known for: warm autoantibody enhancement
|
tube PEG (though gel and SP are pretty good at this)
|
|
in comparing Tube LISS, Tube PEG, Gel and solid phase testing, which is the less sensitive
|
tube LISS (the others are roughly equal sensitivity
|
|
in comparing Tube LISS, Tube PEG, Gel and solid phase testing, which is best known for: having stable reactions (ones that can stick around so the supervisor can review)
|
Gel and solid phase
|
|
in comparing Tube LISS, Tube PEG, Gel and solid phase testing, which is best known for: being expensive
|
gel and solid phase
|
|
in comparing Tube LISS, Tube PEG, Gel and solid phase testing, which is best known for: being able to be automated
|
gel and solid phase
|
|
name three AHGs you might use in the lab and what they might mean (2)
|
-polyspecific antiIgG, anti C3d
- anti-IgG - pretty good at just recognizing IgG -anti-C3b or C3d - id's complement fixation (and hence pretty good at detecting IgM which fixes complement |
|
what is another name for check cells
|
coombs control
|
|
what are check cells
|
positive control to make sure AHG is there and working (esp needed when a wash step is present
|
|
what type of testing doesn't necessary require check cells
|
gel testing
|
|
what does prewarming do to alter compatibility testing
|
reduces cold auto and alloantibodies; not to be used proactively but as confirmation of an identified reaction
|
|
what is adsorption and what are the two types
|
a way to remove an antibody by preincubating the sample with antigen-positive rbcs
autoadsorption (incubate with patient's blood; way to unmask important antibodies by removing "predominant" autoantibody) alloadsorption (more directed type specific rbcs to pull out antibodies to individual antigens to unmask others |
|
what are three examples of how to elute an antibody
|
heat, cold or chemical (glycine)
|
|
how can elution be used
|
by eluting abs off of the rbc, you can create mixture of antibodies that you can then challenge
|
|
name four reagents that can be used to alter rbc ag expression
|
DTT and 2ME, ZZAP,chlorquine
|
|
what rbc ag does DTT affect
|
K, Lu, Do, Yt, LW deactivated/destroys
deactivates IgM |
|
what does 2ME do
|
deactivates IgM
|
|
what is ZZAP
|
proteolytic enzyme and DDT action
|
|
what does chloroquine do
|
strips IgG from DAT+cells (does also remove Bg antigens from rbcs)
|
|
for confirmation of ABO blood type/rh from blood center unit, what is necessary
|
1. forward confirmation of ABO blood type (unit's rbcs with reagent antibodies)
2. Rh D negatives only (weak D not required) |
|
name 2 preanalytical controls on blood sample acquisition
|
- labeling by bedside
- two identifiers |
|
what is the q3 day rule and who, possibly, could deviate from that
|
day 0 is day of draw, then days 1, 2, 3
technically only required for someone pregnant or transfused within last three months but most BB just make it simple and apply it to everyone |
|
how long required to keep sample post transfusion
|
7 days
|
|
what type of tubes are acceptable for compatibility testing
|
red (serum) or lavendar (plasma)
|
|
what type of tube is preferable for blood collection for solid phase and gel and why
|
plasma (lavendar); b/c not fully clotted blood can result in debris that interfers
|
|
what is a disadvantage to using a lavendar top tube in blood compatibility testing
|
the EDTA in a purple top can interfere with complement-dependent antigens
|
|
what are two fx you might see in a specimen collected for blood compatibility testing that would make you "reject" the sample
|
- hemolysis
- lipemia |
|
what is required to test the PATIENT sample in blood bank
|
1. ABO - forward and reverse
2. Rh - IS (polyclonal/monoclonal anti D) 3. antibody screen (see separate flashcard |
|
how should partial D's be classified in patients, in donors? how should weak D's be classified in patients, in donors?
|
- partial D - should be (in recipient) called D neg
- weak D should be (in recipient) be called D pos In donors, weak or partial D should be D pos |
|
in an ab screen as a component of compatibility testing, when does the antibody detection need to be read
|
so, three phases - IS, 37 and IAT, must be read after AHG, at least (and with Gel or SP, this is all you are reading at)
|
|
when should cross check with patient records be performed and what is required in that check
|
immediately after testing patient sample and before cross-match
- check previous ABO/rh testing of at least last 12 months (1/3 significant antibodies disappear in one year; 1/2 significant antibodies disappear in 10 years) |
|
in component selection, what is required for whole blood
|
ABO identical to recipient
|
|
in component selection, what is required for rbcs
|
ABO identical to recipient's plasma
|
|
in component selection, what is required for granulocytes
|
ABO identical to recipient's plasma
|
|
in component selection, what is required for FFP
|
ABO identical to recipient's rbcs
|
|
in component selection, what is required for platelets
|
some say anything goes: preference: ABO compatability preferred, esp if thinking about giving O to nonO patients, esp if young)
|
|
in component selection, what is required for cryo
|
anything goes
|
|
in component selection, what is required for rh
|
if premenopausal female: D neg (unless emergency)
|
|
can you give D neg males D+ blood
|
in trauma setting, absolutely! postmenopausal women too UNLESS HAVE D ANTIBODY
|