Intro Flashcards
1
Q
_____ cells contain histamine and proteins important for killing parasites, increased in allergies
_____ cells contain histamine and vast-active inflammatory mediators, and are responsible for hypersensitivity rxns (like anaphylaxis to a BEE)
A
- eosinophils
- basophils (and mast)
2
Q
Granulocytes are of _____ (lymphoid or myeloid) lineage (i.e., come from lymphoid or myeloid progenitors) and are classified as _______(leukocytes, myelocytes )
A
Come from MYELOID (myeloid stem cell»_space; myeloid progenitor»_space; myeloblast» eos/basis/neutros)
But are classified as LEUKOCYTES (i.e., a WBC)
3
Q
What cells are granulocytes (4)
A
- myelocytes» neutrophils, basophils, eosinophils
- monocytes (»macrophages)
4
Q
Neutrophilic granulocytopenia are at risk of ______ (viral, bacterial, fungal, all, none?) infection
A
-bacteria and fungi
5
Q
- **pathogenesis of granulocytopenia (3 categories)
- production?
- loss?
- ______(organ) problem?
*how does bone marrow exam assist in dx?
A
1-decreased production
2-increased loss (infection, autoimmune prob)
3-increased sequestration (big spleen)
*marrow aspiration (fatty/periphery) or biopsy (core): about 60% should be blood-forming cells(pink/purple), if LOTs of fat (white blobs) = PRODUCTION PROB
6
Q
Lymphoid stem cells come from ______ while myeloid stem cells come from ______
A
*both come from MARROW!
7
Q
Stem cells»_space; ____ cells which form “colony forming cells” (CFU)
A
Stem cells = undifferentiated, potential to differentiate to multiple lineages, self-renewing, can replicate without differentiating
Progenitor cell = ability to form colonies in tissue culture
8
Q
*cytokines that drive differentiation from myeloid progenitor cells (CSF, E, TPO):
_____»_space; RBC
____»_space; monocytes/granulocytes
_____»_space; platelet
A
E = erythropoietin (stim by low o2 for ex) CSF = colony stimulating factor (G-CSF = granulocytes; M-CSF = macrophages) TPO = thrombopoeitin-induced differentiation
9
Q
***what causes marrow failure (decreased production of hemato cells) (3-4)
A
- chemo and/or radiation (very common)
- colonial myeloid hemopathies affecting marrow fxn (AML, MDS) - less common
- invading malignancies (lymphoma, myeloma, metastasis etc)
- aplastic anemia (extremely rare)
10
Q
Post-splenectomy can lead to ______(Inc or dec) granulocytes
A
- increased
- spleen can “sequester” these cells so big spleen can lead to neutropenia
11
Q
Elevated eosinophil count maybe due to IL-_____ or due to _________ (ex?) neoplasms
A
IL- 5! - produced by Th2 helper cells (important for eosin chemotaxis)
Or MYELOPROLIFERATIVE NEOPLASM = neoplastic lymphoid cells (T-cell lymphoma, leukemia, Hodgkins)»_space; also produce Il-5
12
Q
1 Hemoglobin has ____(#) of heme molecules
A
4 heme units … In each of the 4 chains (2 alpha, 2 bet)
13
Q
T/F - hemoglobin does not affect the solubility of o2 in blood, just helps with transferring of o2 to tissues
A
FALSE …. Increases o2 in blood by 70x
14
Q
3 types of hemoglobin (A, F, A2?)
A
A = 2 alpha, 2 beta chains (>95%) F = 2 alpha, 2 gamma A2 = 2 alpha, 2 delta
15
Q
Describe cooperative o2 binding in hgb
A
Increased amount of binding»_space; helps more bind
Also helps with getting o2 off (more that is off, easier it comes off)
**makes the curve s-shaped, in stead of linear
16
Q
How does 2,3 - BPG affect hgb and o2 binding?
- increased in ______(lungs or tissue)
- increase causes curve to shift to ____(L or R)
A
- converts from relaxed (R) structure to tight (T) structure = low o2 affinity state»_space; FAVORS UNLOADING (shifts curves to RIGHT)
- produced in areas of high metabolism
17
Q
Will Inc or dec of each cause LEFT SHIFT of O2 curve:
- temp
- H+
- CO2
- 2,3 BPG
Left shift = favors ____(loading or unloading)
A
Left shift (favor loading, LUNGS) = decreased temp, decreased H+ (higher pH), less CO2, less 2,3 BPG
18
Q
Person living in very high altitude will have o2 dissociation curve shifted to _____(L or R)
A
LEFT (like LLAMAS) … Less pO2 in atmosphere … So need to bind given % (y-axis) at lower po2 level (X-axis)
19
Q
Iron needs to be in _____(ferrous or ferric) state which is ______(Fe2, or 3) to bind o2
A
Ferrous, FE2
20
Q
“Porphyrias” are disorders Chx by defect in _______ synthesis
A
HEME synthesis (lots of different enzymes involved in mitochondria)
21
Q
Dx?
- episodic severe abdominal pain, muscle weakness, personality change and seizures
- alcoholic with hepC, no dark urine, only cutaneous symptoms (painful blistering lesions)
A
- Acute intermittent porphyria
- porphyria cutaneous tarda
22
Q
T/F - hemoglobinopathies are exceedingly rare and are characterized by defects in beta or alpha chain production
T/F- majority of hemoglobinopathies have little clinical significance
A
FALSE … ~500k born with it (most as evolutionary way to get around malaria) = defects concerning hgb structure and or red cell membrane or enzyme defect
TRUE (100s of mutations described - make high or low affinity hgb usually as evo advantage)
23
Q
Thalassemia
- definition
- is alpha or beta thal more common
A
- alpha or beta chain production problem
- alpha rarely a problem due to gene duplication
- beta due to multiple mutations (promoter, frame shift, splicing etc) = MORE COMMON
24
Q
Does each produce mild, severe or no anemia:
- silent alpha carrier (alphaalpha, alpha-)
- beta thalassemia major (beta0, beta0)
- alpha thalassemia trait (alpha-, alpha-)
A
- none
- severe
- mild
1 and 3 very common in African American!
25
Thalassemia (b-major) will cause bone marrow _____(atrophy or expansion)
EXPANSION IF (like in b-major) patient is ANEMIC ... Marrow trying to make more RBC
+++ increase in hematopoeisis and erythropoietin
26
T/F - Hgb A is increased in people with beta thalassemia
FALSE ... Hgb A = Alpha and beta chains
If no Beta ... Then make more F and H2, less A
27
- why does hemoglobin need to be broken down?
| - what happens to the heme group and the iron?
- needs to be broken down because RBC get worn and defective >> get phagocytcized by RES spleen and liver (to lesser degree)
- iron bound to transferrin and reutiilized
- heme broken down by macrophages into bilirubin >> conjugated >> secreted into gut
*enzyme prob -- get more bilirubin, benign condition (potentially even beneficial)
28
What is methemoglobin? What are clinical features?
- hgb that has Fe3 instead of Fe2 ... Doesn't bind o2 as well >>> get bluish tint especially around mouth and extremities
- can be caused by drugs or structural changes (hemoglobinopathies)
29
Describe problem that results from:
- hgb S
- hgb C
- hgb E
S - higher in AA, deox form polymerizes and LEDs to cell rigidity and hemolysis (heterozygous has no phenotype)
C - central W Africa, homo has mild hemolytic anemia
E - homo has mild microcytic anemia
30
* *describe importance of hgb switching
- _____hgb (A, F, A2) predominates before birth and ______ predominates after birth
- switch is due to downreg of ____ subunit (alpha, beta, gamma, delta) and upreg of _______ subunit (a, b, g, d) after birth
- Hgb F >> Hgb A
- alpha high throughout
- switch from high gamma to high beta after birth (f has higher affinity for o2 so can steal it from mom)
31
List the modifications that can be applied to each blood product and their indications, including leukoreduction, irradiation, phenotypic matching, washing, and volume reduction
List the potential side effects of blood product transfusion, both infectious and non-infectious
Compare and contrast immediate and delayed transfusion reactions
LO - transfusions 1
32
***List the modifications that can be applied to each blood product and their indications, including leukoreduction, irradiation, phenotypic matching, washing, and volume reduction
(Explain why we do each)
LEUKOREDUCTION - reduction of WBC (decreases febrile rxns, CMV transmission, HLA immunization) ~80% of transfusions have this
IRRIDATION - gamma rays>> prevents Gvs.H (Tobias! donor T cell attack recipient) by making CD8 incapable of proliferating
PHENOTYPE MATCHING - (C/E/K RBC matched for SICKLE cell patients)
WASHING - remove plasma proteins and antibodies
Vol reduction -
33
Which reduces the risk for febrile transfusion reactions? (leukoreduction, irradiation, phenotypic matching, washing, and volume reduction)
LEUKOREDUCTION ... Because if WBC sit there for a while it can make cytokines or anti-leukocyte antibodies in blood that can cause fever in receipient
34
What can we do to blood product to prevent alloimmunization / CMV transmission?
LEUKOREDUCTION:
Alloimmunization (reduced quantities of HLA-antigens in blood product so people are less likely to make antibodies to HLA antigens – big problem in transplant)
CMV-transmission (reduced virus-burden in blood product
35
What do we do to prevent transfusion associated graft versus host disease? (leukoreduction, irradiation, phenotypic matching, washing, and volume reduction)
Gamma irradiation
36
Who do we want to give transfusions WITH gamma irradiation:
- -Recepient with AIDS
- -Recipient from family member
- N (trick Q since want to give to immunocompromised patients usually, but for some reason HIV does not have increased risk of GVD)
- Y (because of HLA common types can trick body to attack)
37
Match each transfusion technique (leukoreduction, irradiation, phenotypic matching, washing, and volume reduction) with goal:
- -prevent graft vs. host in immunocompromised person
- -patient with IgA deficiency
- -patient with anaphylactic rxn to previous blood product
- -prevent RBC alloimmunization in patient with sickle cell
- -irradiation
- -WASHING
- -WASHING = removes protein/antibodies (Indicated for patients with anaphylactic reactions to prior blood products (RISK = patients w/ IgA deficiency can react to IgA in plasma)
- -PHENOTYPE MATCHING
38
Match transfusion product (RBC, platelet, plasma, cryoprecipitate) with each:
- -liver failure
- -thalassemia
- -patient with coagulation factor deficiencies
- -patient with dysfibrinogenemia or hypogibrinogenemia
- plasm (has multiple coag factor def)
- RBC
- plasma
- cryo
39
T/F- transmission of HIV, HCV, HBV and malaria via transfusion are exceedingly rare
TRUE! Because of screening and because of testing*
*esp NAT (nucleotide) testing has really decreased risk of HIV and hep .. Because can detect viruses VERY EARLY when previously it would have been missed via antigen/antibody testing
40
* *acute hemolytic transfusion rxn
- #1 cause?
- often due to recipient getting _____ (O, A, AB, B) blood
- fatality rate / incidence?
- SYMPTOMS?
ACUTE - #1 cause = clinical error, present with fever, chill w/in few hours (usually first few minutes) .. Usually from antiA or antiB blood
ex - O+ getting A+ (nurse screw up) >> get hemolysis
Fatality >10%; ~1 per 25k incidence
RX = Stop transfusion, flush with IVF, consider diuretics, monitor for DIC and renal failure
41
* **Delayed hemolytic transfusion rxn:
- CAUSE?!
- get ______(intra, extra) hemolysis
- appears ______(days) after infusion
- previous alloimmunization to RBC antigen (exposed to red cell >> formed antibodies to kell for ex (but transient!) >> come in few years later (don't seen antibodies) >> B-cells primed to make anti-kell rev up again
- intra and/or extra
- 3-14 days
42
Explain indirect vs direct Coombs test?
INDIRECT = take sample of plasma (yellow, top of tube) >> add RBC >> then add anti-human antibody (Coombs reagent) which will bind to any antibody on the RBC and "glutinate them" (clump them)
DIRECT = take sample of RBC (red, bottom of tube) >> add Coombs reagent >> precipitate indicates POS result (like above)
So indirect - you take out plasma with the antibodies .. Then add RBCs ...then add coombs
For DIRECT - take out RBC (AB already attached if present) ... Then add Coombs
43
What does Coombs reagent indicate?
Just binds to any IgM or IgG ... If Positive then it shows that SOME SORT OF ANTIBODY IS ATTACHED TO THE RBCs = PROBLEM! (Could be allo or other antibody)
**add it because the IgM/IgG on the RBC won't clump (glutiante) by themselves so Coombs is just a way to see if they are there
44
Febrile nonhemolytic transfusion rxn:
- how to distinguish from acute hemolytic TR?
- occurs because of ______ (usually)
- do _______ (technique) to prevent
- CAN"T! (So stop and call blood bank immediately to make sure it's not AHTR (i.e., wrong type given))
- both present with fever and chills
- usually occur from cytokines released from WBCs left in the unit ... Why we do leukocyte reduction
45
Which situation would you be able to RESTART the transfusion for:
- acute febrile
- febrile nonhemolytic
- uticarial rxn
- TRALI
UTICARIAL = occurs in 3%, get rash and itching .. Because recip is sensitized to soluble allergen in the plasma a of the donor ... Resolves with stopping transfusion +/- histamine
46
Is each acute or delayed; febrile or non-febrile:
- -iron overload
- -TRALI
- -bacterial contamination
- -allergic rxn
- -volume overload
- -post transfusion purpura
Delayed non-febrile = post purpura; ironed overload
Acute Nono-febrile = allergic (anaphalytic, uticarial); volume overload
Delayed febrile = delayed hemolytic, DvHD
Acute febrile = acute hemolytic, febrile nonhemolytic, TRALI, bacterial contamination
47
Transfusion related acute lung injuries (TRALI):
- febrile or not
- cause?
- symptoms?
- -acute febrile
- -Usually due to anti-HLA/neutrophil antibodies from DONOR that attack recipient WBC
- -looks like ARDS, get white out on chest X-Ray
48
What is difference between TACO and TRALI transfusion complications?
-acute/delayed ; febrile non-febrile?
*both are acute, and both present with lung probes
TACO - usually NOT febrile; has PULM EDEMA and upper lobes are darker than lower lobes; get signs of HF and HTN = from VOLUME OVERLOAD (to young person or weak heart)
TRALI - FEBRILE; white-out everywhere because of HLA antibodies from donor that attacks WBC; looks like ARDS
49
What naturally occurring antibodies will each blood type have:
- O
- A
- B
- AB
Ig____ is main antibody
- antiA and antiB
- antiB
- antiA
- no antibodies
*igM is the major class of antibody produced against ABO groups
50
Blood group O has ____ (H, A, B, neither) antigen
| Groups A and B have _____ antigens
O has H ... Added by alpha1-fructose transferase
A and B also has H + A/B
After a1-2FucTs adds H >> A or B transferase adds the A and/or B antigens
51
- Ig____ does not cross placenta, but Ig____ does (A, M, G)
- thus the anti-Rh(D) antibody that is problem is Ig____
- Rh___(+/-) moms exposed to fetal Rh____(+/-) blood which will lead to hemolytic disease of subsequent newborn with Rh_____(+/-)
- mom should be treated with ______ after 1st pregnancy to avoid this
- IgM does not, IgG does
- Rh- moms exposed to Rh+ kids >> mom makes anti-Rh (anti-D) >> attack the next Rh+ kid
- treat mom with antiD-IgG(RhoGAM) during. 3rd trimester and after each pregnancy to prevent anti-D IgG formation
52
Extended blood phenotype (C, E,K , Kell, Duffy) matching typically only performed on patients with ______ and on select patients with _______
Typically only performed on patients with sickle cell anemia and on select patients with autoimmune hemolytic anemia
53
The "minor" anti-RBC antibodies can cause _____(acute hemolytic, or delayed hemolytic) transfusion rxns
BOTH
May lead to immediate hemolytic transfusion reactions
●“Pre-formed” antibodies, often anti-A
May lead to delayed hemolytic transfusion reactions
●Anamnestic responses to “minor” RBC antigens
54
- -Describe screening vs. typing in transfusion?
- -does screen involve indirect or direct Coombs?
--What's difference between type and cross vs. type and screen?
Type = just testing for A, B O
Screen = Indirect antibody test (IAT)
●Mix patient plasma with RBCs of known antigen specificity and add Coombs reagent (INDIRECT COOMBS)
TYPE AND CROSS (Done AFTER a TYPE AND SCREEN; so includes both typing and screening):
●Crossmatch: mix patient plasma with donor RBCs from a segment
●Reserves units for the designated patient
●Good for 3 days
55
Would we do "type and cross" or "type and screen" for following:
- -G2P1 woman in for 12 wk prenatal checkup
- -13 yr old girl about to get transfusion before surgery
- -type and screen (check ABO and RH status)
- -type and cross (check ABO and then actually mix with the donor blood to see if OK)
* *Only T& if about to transfuse cause only good for 3 days after you cross it!
56
______(indirect/direct) Coombs test used to detect antibodies in recipient serum by mixing plasma with RBCs of known antigen
______(indirect/direct) Coombs used to detect antibodies bound in Vivo by mixing RBC from recipient with Coombs reagent
______ may be used in autoimmune hemolytic anemia patient to see if allo antibodies present after transfusion
- indirect (test for specific antibody in serum)
- direct (just testing whether they have antibodies on their red cells)
- direct
57
What is alloantibody?
an antibody that reacts with an antigen from a genetically different individual of the same species (allo antigen)
58
* **which are platelet antigens:
- ABO?
- Rh?
- HLA?
- other?
- yes
- no
- yes
- platelet specific glycoproteins antigens
59
Clinical implications when we should consideranti-platelet antibodies (3)
--Thrombocytopenia
--Platelet refractoriness
●Anti-HLA antibodies
●Anti-platelet glycoprotein antibodies
--Neonatal alloimmune thrombocytopenia (NAITP)
60
What coag factors found in cryoprecipitate? Used for ______ disease
VWF and factor 8 (Plus 13, fibrinogen and fibronetin) .. Used for hemophilia ; hypogibrinogenemia, F8 deficiency
61
T/F - platelets should be stored at 4C to avoid bacterial contamination
FALSE ... Can't be stored at 4C or they breakup or something ... Reason why bacterial contamination are so common with platelet transfusions unfortunately
62
T/F - fresh frozen plasma contains ALL coagulation factors plus fibrinogen
T/F - fresh frozen plasma contains platelets
- TRUE
- FALSE! (Frozen makes them non-functional) *
*note - platelets ARE in normal plasma tho
63
10-15 cc/kg of pRBCs raises hemoglobin approximately_____
2-3 g/dL
64
Give what (RBC, platelets, cryo, frozen plasma) to:
- -anemic patient at 6g/dL
- -person with thrombocytopenia from deficiency
- -person with thrombocytopenia because of destruction
- -person with DIC
- -liver disease
- -person with gun shot given RBCs already. PT of 18, PTT of 50sec, fibrinogen
- RBC
- platelets
- none?
- frozen plasma (b/c coag factor deficient!)
- frozen plasma (coag factor deficient!)
- cryo (to replace fibrinogen)
65
Person with O blood is universal ____(donor/acceptor) of RBCs but universal _____(donor/acceptor) of plasma
- donor of RBC ... Has no antigens
| - acceptor of plasma ... Because has all of the antibodies so doesn't matter what antibodies are in the plasma
66
Which is problem (more than 1 possible):
- give A person AB plasma
- give B person AB RBC
- give O person AB plasma
- give AB person O plasma
- no prob (AB has not antibodies in plasma)
- problem (has antiA antibodies that will attack AB RBCs)
- not a problem
- problem (has anti-A and antiB antibodies ... Will attack AB RBCs)
67
MCV is ______ in early vs. late iron deficiency anemia
early = normocytic (stored iron goes down, marrow compensates)
late = microcytic (marrow can't compensate >> RBC divide too many times to try to compensate for less Fe) .. trying to maintain their "pink color"
68
hypersegmented neutrophil classic in _____ vitamin deficiency and would expect _____ (microcytic, normocytic, macrocytic) anemia
b12; macrocytic anemia
69
*will have essay questions based on anemia and should follow rapkins algorithm...
1st - do RETIC test if have anemia
2nd - then do ______ if its high or ______ if its low
*go with retic >> then MCV if low
or DAT if high >> then smear if DAT is neg
70
**what are RETICS ?
--High retic count signals _____(destruction / production prob) while low count signals _______
- if high retic, negative DAT = ____ (ddx)
- if high retic, positive DAT = _____ (ddx)
immature/newly formed RBC
- -HIGH retic = INC LOSS (normal bone marrow cranking out more and more naive RBC (retics) to compensate)
- -LOW retic = DEC PRODUCTION (aplastic anemia, early iron def/ACD, chronic kidney disease)
- AIHA (autoimmune)
- not autoimmmune >> do SMEAR >> inborn or aquired
71
hypothyroidism will have _____(high/low/norm) MCV and ______(high/low/normal) retic
- high MCV, low retic = MACROCYTIC
| * same category as pregnancy (inc demand for folate) and b12/folate deficiencies
72
T/F - hgb is a percentage that reflects both water and hb while hct is a direct measure
False, opposite
73
iron deficiency anemia will ahve _____(high/low/normal) RDW
RDW = difference between big (normal) and small (new microcytic, too many divisions) RBCs
-so HIGH RDW = two cell pops
74
B-thal minor has increased _____(HbA2, HbC, HbF) and B-thal major has increased _______
- which is associated with erythroicyte hyperplasia (chipmunk face)
- what is histology chx?
- what type of anemia does each lead to?
B-thal minor = inc HbA2 (diagnostic >3.5%)
B-thal major = inc HbF >> marrow expansion (chipmunk, "crew cut" x-ray)
histology = target cell (reduced heme in cytoplasm like air in basketball) >> blebs in the middle
MICROCYTIC
75
dx?
| -old alcoholic presents with anemia, high MCV, low retic, glossitis, high serum homocysteine, normal methylmalonic acid
folate deficiency (normal MM acid = distinguishes it from B12 deficiency where MM is high becuase b12 cant convert it to SCoA)
76
extravascular hemolysis has _____(high/low) retic while intravascular hemolysis has _____(high/low) retic
both have HIGH retic (inc destruction)
77
dx? (is each macro, normo, or microcytic)
- anemic patient with spherocytes, increased MCHC, increased RDW
- anemic patient with back pain and hemoglobinuria after eating fava beans
- anemic kid with sausage fingers
- mild anemic patient with heme crystals on smere
- hereditary spherocytes (norm, extravasc)
- G6PD deficiency (norm, intra>extravasc)
- sickle cell (norm, intra> etravasc)
- hemoglobin C (norm, intra>extra)
78
does each have high or low retic
>> If low what is MCV?
>> If high, is it non-auto immune or auto-immune
- -chornic kidney disease
- -non-autoimmune aquired (heart valve, infection, burns, toxins)
- -autoimmune hemolytic anemia (IgG, IgM)
- -Paroxysmal noctural hemoglobinuria
- -thalesemia
- -pregnancy
- -aplastic anemia
- -low, norm = non-hemolytic
- -high (non-auto)
- -high (auto-immune)
- -high (non-auto)
- -low, micro
- -low, macro
- -low, norm = non-hemolytic
79
In response to intracellular bacteria get activation of macros and ____ (NK, T, B, macros) in innate immune and ______ and ______activation (NK, T, B, macros) in adaptive immune response
innate macros activated by ______cytokines (4)
adaptive macros activated by _____ cytokine (1)
```
innate = NK and macros (IL-1, 6, 12, TNF-alpha)
adaptive = effector Ts and macros (IFN-gamma)
```
80
match these (salmonella, encapsulated bacteria, viruses) with ...
- -granuloma formation, cytokines, TcH
- -complement, spleen, TcH
- -TcH, TcC, NK
- salmonella (INTRACELL!)
- encap
- viruses
81
if you lack _____ (complement) you're at risk of N. meningitis
C9 ... can't make MAC
82
salmonella and mycobacterium are rely on _______(interferons/cytokines, complement, spleen, B-cells)
why?
interferosn/cytokins ....becuase they are intracellular bacteria
83
* **cystic fibrosis
- defect in _____ channel cuases lung secretions to become _____(More or less) viscous
- ____(lowers/raises pH) and _____(lowers/raises) neutrophil count while ______(lowers/raises) elastase
*def of bronchiectasis?
- defect in CTFR (Cl) >> inc VISCOUS secretions (more mucuousy) >> inc infections in LOWER airways
- lowers Ph >> molecuels stop functioning >> neutrophils go UP >> release free radicals (to kill bacteria) and ELASTASE
- BRONCHIECTASIS - chronic infection/absessces >weakens airway >> can collapse when try to EXHALE >> get "AIR ABSCESS" (Act like abscess because walled off so antibitoics can't get to etc)
84
T/F - chemotherapy targets cells in mmarrow and thymus but those in organs (matureT cells, spleen etc) are nto affected
TRUE ... cause chemotherapy targets rapidly dividing cells
85
rituximab does _______
- mech
- used for ___ diseases
monoclobal antibody that KILLS B-CELLS!
- used for B-cell lymphomas with CD20 expression
- now used for variety of autoimmune diseases with too much antibodies (Lupus, ITP etc)
- SE- hypogammaglobulinemia, repeat viral infections, lack of IgA (mucosal based infections! in sinus and GU), compelment less effective (inc encapsulated. and atypical infections)
86
Ig_____ is important for fighting mucosal based infctions
A
87
T/F - splenectomy increases risk of sepsis but has minimal effect on complement
FALSE ... increased risk of sepsis (5% prevlaence) and decreased ability to phago complement
88
T/F - person with splene has same resposne to vaccines as person without
T/F - splenectomy causes decrased APC
- false (Decreased rsposne without)
| - true
89
*pro-inflammatory agents (IL-2, tumor vaccines, PD-1 inhibitors ) can be sued for ______ (3) cancers
- renal cell
- melanoma
- lymphoid malignancies
90
ipilimumab
- mech
- used for?
Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.
Cytotoxic T lymphocytes (CTLs) can recognize and destroy cancer cells. However, an inhibitory mechanism interrupts this destruction. Ipilimumab turns off this inhibitory mechanism and allows CTLs to function.
*MELANOMA
91
*NEUTROPENIA = neutrophil count that is _____ (# of SD below mean)
T/F - count of 900 has high risk of infection
2SD below mean ..
92
Chediak Higashi diseease involves ______ (aspect of neutrophil dysfunc) while chronic ganulomatous Disease iivolves ________
choices: margination, adhesion, diapadesis, chemotasis, phagocytosis, oxidation
CH = microtubule defect so can't traffic intracell contents well (ie, can't transport phagosome to lysosome to be destroyed) = PROBLEM WITH PHAGOCYTOSIS
CGD = impaired OXIDATION (deficiency in superoxide production in PHOX gene >> neutros ingest bacteria but cant kill them
93
chronic granulomatous disease causes increased infections from ________(catalase?) organisms
-this inhibits _______(neutrophil or macros)-mediated killing and requires instead ______(neutroiphil or macros) to do the job.
catalase + ... becuase it inhibits h2o2 = this is how NEUTROPHILS KILL!
so instead require MACROS to come in and clean it up but they just make a mess = GRANULOMA
infections in 1st year of life (pneumonia, abscess, arthritis, osteomyelitis)
organisms = staph A, serratia, listeria, ecoli, klev
94
use _______(chemotherapy, steroids, both) in ALL
both ... trying to clear marrow of all malignant cells then let their marrow reccover (induction is first month of therapy >> then ANC 0 during first 21 days after as normal cells take 21 days to recover)
95
T/F - person with neutropenia with fever should be treated with broad spectrum antibitoics BEFORE physical exam
T/F- stopping antibiotics with neutriopenia is dangerous
TRUE ... cause if neutropeni then no innate immunity and no inflammatory response so may have no signs and symptoms of infection but if fever there could be
BROAD SPECTRUM (- to cover GI, + to coverskin and mouth, anaerobes for mouthm anus and abscesses)
TRUE - 50% of peds will respike
96
- what antibiotics should be give for person with neutropenia with low risk (cover gram Neg)
- what about if abdominal pain
- what about high risk
CHOICES - ceftraxadime, meropenum, vancomycin, meropenum
T/F - ceftraxadime is ____ generation cephalosporin that is good for LOW AND HIGH RISK
low risk = 3rd gen ceph (ceftraxadime) or anti-pseudo (piper)
Ab = cover anaerobes (meropenum)
High risk = cover gram positives (ceftraxadime, vancomycin)
TRUE! (3rd gen)
97
Prognosis of AML if:
- normal karyoptype
- chr 16 inversion
- chr 5,7,8 complex
- t(15,17)
- t(8,21)
- OK
- bad
- good
- good
98
what is clinical presentation of AML?
- low grade fever/infections
- fatigue, dyspnea palpitations ROARING IN EARS
- bruising/bleeding
99
dx? bone pain worse at night, tired, vision, dyspnea, brusiing, roaring in ears
AML
100
what cancer is MPO+
acute myeloid leukemia (myeloidperoxidase)
101
***AML TREATMENT PRINCIPLE:
1st chemo you give ____ (when) for AML is _______ >> assess response with BM biopsy >> ____(minority or majority) will be "CR" = ____? >> consolidation therapy = ______ for _____(CR+, CR-, both)
*when do we do BM transplant?
- INDUCT IMMEDIATELY (if active disease) >> with anthracycline araC
- majority (60-70%) CR (level just below level of detection) >> but NOT CURE!!! (CR for 5 years)
- colsidate with high-dose Ara-C
*risk stratify after induction .. so after consolidation eithe TRANSPLANT or OBSERVE
102
rx for acute promyelocytic leukemia?
RA and arsenic
RA = retinoic acid (specificially all -trans- RA) >> binds toaltered RAR recpetor (blocking maturation of promyelocytes) >> allows blasts to mature then Die
103
predicted survival is ____(good or bad) if AML patient relapses (YOUNG v OLD)
HORRIBLE for BOTH ... signals that they are resistant to chemo
104
T/F - AML remains fatal disease for majority of adult patients
TRUE ... seeing it more in older ages now, and doon't do as well
105
T/F - stem cell transplant invovles giving similar chemotherapy agents as non-transplant patients except that dose is greater
TRUE ... give high dose to drop everything to zero ... then give marrow or what not to RECOVER
106
what are main indications for HSCT (main 3 )
- MYELOMA! (mostly auto)
- NHL (mostly auto)
- AML (mostly allo!)
- -- big 3 ! ---
- Hodgkin
- ALL
- CML
Not indicated. - non-hodgkin, CLL (few)
107
what is difference from autologous vs allogenic HSCT
auto = patients own cells ... take fresh and preserve
it
allo = from related (1/2 match mom/dad/sib) or unrelated or core blood ... criogenically freeze it for later
108
how do we "condition" patient prior to HSCT?
chemo alone or chemo with radiation
non-myeloablative condition = less intense (for ex if patient has severe infection or soething) = ... induce myelosupression... have a more "mixed chimerism" (combo or donor and own T cells) >> GVL? with cure of malignancy
109
when do you get severe myelosupression, GI toxicity, NV/ mucositis etc (pre-infusion, pre-engraftment, post engraftment)
PRE-ENGRAFTMENT ... right have SC infusion!
110
describe engraftment in HSCT? what do we have to do before and after
- ___ and ____ are adhesion molecules that are required for engraftment
- measure engraftment via ______
ENGRAFTMENT = when infused stem cells get into the marrow (takes approx 10 days from infusion) >> start differentiating !
- for that first 10 days post "transplant" = need to infuse platelets, WBC, RBC, everything!
- VLA-4 and CD34
- VNTR (variable number tandem repeats) ... take sample from host, want to make sure BANDS are same donor (like a PCR gel!)
111
describe GVHT
| -does it happen _____(after infusion or after engraftment or both)
- donor T cells recognize host antigens >> start destroying
- Il-12 = made by host APC >> make donor T into Th1 >> make IFN-gamma (recruit more macros) and iL2 >> NK and CTL differentiation >> KILL CELSL!
AFTER ENGRAFTMENT!
112
Acute v. chronic GVHD complications
SIMILAR - arbritary 100 day cutoff post engraftment
primary organs affected in the acute process are skin, liver and gastrointestinal (GI) tract, although other sites may be affected.
CHRONIC
- rash >> can get ulcerations
- faschiatis (wrist and fingers and skin are "TIGHT") ??
- DRY/RED EYES and DRY MOUTH
- mouth ulcers (mucositis)
113
are the following pre- or post-engraftment complications: fever, nausea, vomiting, mucositis, anorexia
PRE-ENGRAFTMENT
fever - because have no immune cells!
114
T/F - JAK2 INHIBITORS can be used to treat GVHD
| T/F - blocking JAK/STAT pathway can increase risk of replase post HSCT
TRUE - blockc phosphorylatin leading to blocking T-cell activation
FALSE - DON"T increase risk of relase
115
We use chemotherapy for ______(auto/allogenic HSCT) and immunotherapy in ____(auto/allo) HSCT
chemo for auto +/- immuno for allo
116
renal failure causes _____ anemia (retic, MCV?)
normocytic, low retic (LOW PRODUCTION because low erythropoietin)
+ shortened survival and increased loss in urine
117
what 3 endocrine probs cause normocytic anemia?
```
Androgen deficiency (M usually have
Hypothyroidism (initially, then becomes macrocytic over time)
Adrenal failure (low cortisol levels)
```
118
tear dropped erythrocyte in anemic patient indicates ...
marrow failure or marrow replacement
119
marrow replacement/failure leads to _____ anemia (retic, MCV)
low retic (low production), normal MCV
120
what is cause if normocytic anemia with low retic, smear shows tear drops and biopsy of bone marrow show lots of GRANULOMAS
Fungal- Histoplasmosis
Mycobacterial Infections
121
high reticulocyte count causes MCV to go ____(down or up)
UP! because retics are big (and blue)
122
ddx? macrocytic anemia, neutrophil have 3-4 segments on smear, see target cells with increased red cell membrane
- liver disease
- obstructive jaundice
- post splenectomy
123
how do you tell apart megaloblastic vs non-mega macrocytic anemia ?
mega = segmented neutrophils (>5)
124
```
what is NOT cause of megaloblastic anemia:
Vitamin B12 Deficiency
Folic Acid Deficiency
Chemotherapeutics
Myelodysplastic Syndromes
Hereditary Defects in DNA Synthesis
```
ALL ARE CAUSES
125
dx? Anemia with low reticulocyte count and high MCV, Increased Indirect Bilirubin, Increased Transferrin Saturation, glossitis
def in folate of b12 (folate more common!)
126
***different in symptoms and labs between folate and b12 deficiency? (homocysteine or methylmalonic acid)
SYMPTOMS = neurological symptoms only in B12 (not always present though)
LAB = HC increased in BOTH, MM acid increased only in B12
**important because can have false negatives in B12
127
dx? anemia patient with high MCV taking methotrexate
folate deficiency (inhibits dihydrofolate reductase)
128
most common cause of megaloblastic macrocystic anemia?
* folate > b12
* most common cause is ALCOHOLISM! (b/c inadequate dietary intake) or diet
other causes of folate = inc demand (pregnancy, cancer) absorption prob (crohn, celiac ) or drugs (methotrexate)
129
* *Alloimmune HDFN/erythro fatalis PATHOPHYS =
- - Destruction of red blood cells (RBCs) of the neonate/fetus by maternal immunoglobulin_____
- -Antibodies are produced where / by who?
- -who is affected (kid, mom or next kid)
- - Destruction of red blood cells (RBCs) of the neonate/fetus by maternal immunoglobulin G (IgG) antibodies
- -Antibodies are produced when fetal erythrocytes, which express an RBC antigen (ex Rh+!) not expressed in the mother, gain access to maternal circulation
- -Maternal IgG antibodies cross the placenta to affect later pregnancies
130
hemolytic disease of newborn / fetus include
1-Alloimmune HDFN (newborn or fetus?)
2- erythroblastosis fettles (nb or fetus?)
- newborn
| - fetus
131
T/F - Rh alloimmunization requires previous exposure to Rh(+) blood, therefore this should not occur in primigravid women
TRUE
132
if mom is ____(ABO) and baby is ____(ABO) then worry about mom having hemolytic event
O mom and baby with A/B/AB ... have antigens that mom's antibodies will attack
so if baby is O don't have to worry!
133
T/F - all moms with ABO incompatible with fetus will have HDFN (hemo disease of fetus/newborn)
FALSE
| ABO incompatibility ~15% of all pregnancies... but ONLY 4% HDFN (0.6 % of all pregnancies)
134
```
For each, are we testing mom or baby ; serum or RBC :
--Direct Antibody Testing (DAT)
= Testing _____
--Indirect Antibody Testing (IAT) =
Testing ______
```
--DIRECT Antibody Testing (DAT) = Test BABY RBCs
(Antibodies attached DIRECTLY to RBCs??)
--INDIRECT Antibody Testing (IAT) = Test MOTHER’s SERUM
(Antibodies to baby’s BRCs present??)
135
T/F - IgM and IgA antibodies are not reactive with standard AHG (anti-human globin = COOMBS) reagent
TRUE
May be made by injecting rabbits, goats or sheep with human C3 (compliment) and IgG >> harvest Ab produced by the animal>> Polyspecific (IgG and C3)
Monoclonal technology may be used to make monoclonal antiglobulin reagent
IgG or C3
136
mom that is Rh ___(- or +) should be given anti-D immune globin (Rhogam) to prevent HDFN
Rh antigen negative mother with NO Rh antibody*
*note - Once alloimmunization has occurred Rhogam is NOT effective for preventing or reducing HDFN for future pregnancies
137
____(warm/cold) -reactive AIHA is more common in kids
WARM (~60-90% of kid AIHA cases)
138
***mangement of hemolytic disease of newborn/fetus (HDFN)
- -Develop hyperbilirubinemia within the first 24 hol (hours of life)
- -Phototherapy +/- hydration
- -Whole blood exchange
- -IVIG (Intravenous Immunoglobin)
139
T/F - ABO allomunization/HDFN generally less severe than HDFN associated with Rh(D) incompatibility
TRUE
140
- -warm autoimmune hemolytic anemia = Ig____
| - -cold AIHA = Ig____
```
warm = IgG (warm weather is GGGReat)
cold = IgM
```
141
```
dx? 5 yr old present with fatigue CBC: WBC 5.6 / Hgb 4.8 (LOW) / Plt 250
LDH: 800 U/L (HIGH)
Haptoglobin: 30 mg/dl
DAT: POSITIVE,
Smear = spherocytes
```
IgG (warm) autoimmune hemolytic anemia (bc SPHEROCYTES! .. as a result of spleen eating membrane with IgG)
142
***pathophys of warm vs. cold AIHA (what Ig is responsible, what has intra vs. extravascular hemolysis)
IgG binds RBCs 37°C, +/-fix complement>> EXTRAVASC hemolysis >> splenomegaly, jaundice, anemia
IgM autoantibodies bind RBCs at colder temperatures + fix complement>> complement-mediated INTRAVASC hemolysis or immune-mediated extravascular clearance (liver)
143
T/F - can see anti-C3 antibodies in both warm and cold AIHA
TRUE
144
Paroxysmal cold hemoglobinuria ?
| -Ig___ mediated
--Almost exclusively in children
Most commonly after a viral-like illness
--IgG autoantibodies bind preferentially at colder temperatures >> fix complement efficiently >> intravascular hemolysis with hemoglobinemia, hemoglobinuria, and anemia
*since likes cold temp see pallor on extremities 1st
145
SERUM MARKERS OF HEMOLYSIS :
___(high/low) indirect bilirubin
___(high/low) LDH
___(high/low) haptoglobin
High indirect bilirubin
High LDH
Low haptoglobin
146
T/F - SCD patients are at higher risk of alloimmunization (why or why not?)
TRUE (allo = developing antibodies to non-native antigens) as a result of transfusion exposure!
Alloimmunization>> difficulty in future crossmatching>> reduces access to compatible blood needed
147
In the absence of minor RBC antigen matching (ABO/Rh), alloimmunization occurs in ____(higher or lower_ % of SCD patients vs. other anemia patients
WHY?
TRUE ... Primarily due to minor blood group incompatibilities between the donor population (predominantly white) and the recipient SCD population (of African descent)
MINOR ANTIGENS (duffy, kell, kidd) are biggest problems
148
dx? 6 yr old with anemia, normocytic, jaundice, pallor and fatigue, cholethiasis
HEMOLYTIC (ex - SCD)
