Fab Classifications Of Aml

Front 1

MO

Back 1

minimally differentiated.
Difficult to tell if myeloid or lymphoid. prominent nucleoli, large, large nucleus. no cytochemical markers, have certain myeloid cd markers, so you may atleast be able to tell they are of myeloid lineage.

Front 2

M1

Back 2

w/o differentiation. very immature, >3% peroxidase +. Few granules/Auer rods.

Front 3

M2

Back 3

w/maturation. full range of differentiation. t(8,21)* CBFalpha/ETO fusion gene. Better prognosis. Granules are more prominent. you may have an auer rod.

Front 4

M3

Back 4

acute promyelocytic leukemia. hypergranular promyelocytes, many Auer rods. the enzymes of these granules are cytotoxic and can cause DIC if chemo, so treat with all-trans-retinoic acit (ATRA) to avoid DIC. t(15,17) RARalpha/PML fusion.

Front 5

M4

Back 5

acute myelomonocytic leukemia. myeloid (granules) and monocytic (convoluted nuclei and vacuoles in the cyto) differentiation. monoblasts + for nonspecific esterase. Inv (16). good prog.

Front 6

M5

Back 6

m5a- monoblasts and promonocytes (delicately folded nuclei. non specific esterase +.

Front 7

M6

Back 7

acute erythroleukemia. mainly adults, poor prognosis. dysplastic erythroid precursors (basophilic normoblasts-blue!) >30% myeloblasts

Front 8

M7

Back 8

acute megakaryocytic. blasts of megakaryocytic origin. Down syndrome at risk. huge blasts with cytoplasmic blebs. express neither MPO or lymphoid markers. no granules, huge nuclei.

Front 9

myeloid sarcoma

Back 9

tissue mass of myeloid blasts

Front 10

monocyte derived cells stain + with

Back 10

non-specific esterase

Front 11

downey type II

Back 11

reactive lymphocytes seen in mononucleosis that are not blasts

Front 12

ALL

Back 12

acute lymphoblastic leukemia. usually b cells. less cytoplasm than a myeloid cell, no granules or Auer rods. dense chromatic, fewer nuclei.

Front 13

ALL presentation

Back 13

more acute, pt presents much sicker. symptoms of bm suppression (low counts), bone pain due to cancer cells secreting cytokines, generalized lymphadenopathy, hepatosplenomegaly, testicular involvement, CNS manifestations

Front 14

Immunoprofile of ALL

Back 14

TdT+, CD19+-early B cell diff
CD10+-marker of early pre-B cell. aka CALLA
Lack of surface Ig would also indicate an immature B.

Front 15

good vs bad prog with ALL

Back 15

good- 2-10 yrs old, hyperdiploidy
poor- <2 yrs old, hypodiploidy. these tend to involve translocations of MLL gene on chrom 11, phila chrom- t(9,22)

Front 16

ALL- L1

Back 16

small cells predominate
no nucleoli
scant cytoplasm

Front 17

ALL-L2

Back 17

large cells predominate
one or more nucleoli
abundant cytoplasm

Front 18

ALL-L3

Back 18

large homogeneous cells
prominent nucleoli
abundand cytoplasm

Front 19

Chronic leukemias

Back 19

No maturation arrest
Predominance of mature cells
Myeloid or lymphoid
Occurs in older individuals

Front 20

CML-what is it? which chromosome?

Back 20

Clonal expansion of myeloid lineage with basophilia (important!) and splenomegaly
Philadelphia chromosome
T(9:22)
Bcr-abl gene rearrangement

Front 21

CML-chronic phase vs accelerated phase vs blast phase

Back 21

-Chronic phase
Duration 3-4 yrs. high white count, fluctuates
-Accelerated phase
counts start to really drop
Progressive maturation arrest
Therapy resistance
More blasts in marrow
-Blast crisis
you could get acute leukemic

Front 22

CML- clinical presentation

Back 22

Clinical features
Splenomegaly
Asymtomatic, LUQ pain, early satiety
Anemia
Hepatomegaly
Purpura
Fatigue, anorexia, weight loss, sweats, hyperleukocytosis, priapism

Front 23

CML- laboratory tests

Back 23

Laboratory tests
LAP
BCR:Abl gene rearrangement
Bone marrow biopsy/aspirate

Front 24

chronic leukemias

Back 24

mature clonal disorders, involve blood and bm, may infiltrate other organs, usually affect older adults. better prog.

Front 25

b-cell chronic lymphocytic leukemia (CLL)

Back 25

chronic lymphocytic leukemial (CLL)
hairy cell leukemia (HCL)
B-cell prolymphocytic leukemia

Front 26

r/o reactive lymphocytes

Back 26

look at age group.
-reactive lymphocytosis: mono, cmv, HIV, rubella, rubeola, varicella
- non-reactive lymphocytosis: pertussis
-transient stress lymphocytosis

Front 27

chronic lymphocytic leukemia (CLL)

Back 27

most common. indolent, but not curable. often asymptomatic, nonspecific, easy fatigue, weight loss, anorexia. may transform into large B-cell lymphoma (RICHTER TRANSFORMATION). smear: lymphocytosis, smudge cells

Front 28

lymph node appearance in CLL

Back 28

loss of normal lymph node architecture. wall to wall small lymphocytes (loss of the lighter follicle center)

Front 29

immunophenotype of CLL

Back 29

CD20+, CD23+ (mature lymphocyte markers)
CD5+ is usually in T cells
surface immunoglobulin

Front 30

Hairy cell Leukemia (HCL)

Back 30

rare. middle age-elderly. tumor cells in bm and spleen. splenomegaly. cells have hair-like projections from cyto. fried egg appearance
stain with TRAP+, Tartrate resistant acid phosphatase

Front 31

B-cell Prolymphocytic Leukemia

Back 31

rare. older patients. Presenting:weakness, malaise, weight loss, abd. discomfort.
prolymphocytes >55% of all lymphocytes
-lymphocytes express CD20 and surface immunoglobulin
-lymphocyte count rises rapidly
-cells larger than CLL cells w/ prominent nucleoli

Front 32

T-cell prolymphocytic leukemia (T-PLL)

Back 32

T-cell prolymphocytic leukemia (T-PLL)
rare. 70 yrs old.
present with splenomegaly, hepatomegaly, lymphadenopathy, skin lesions.
lymphocytes express CD3
prolymphocytes are >90% cells in a smear

Front 33

T-cell large granular lymphocyte leukemia

Back 33

rare. indolent. severe anemia. mature T-cell phenotype. cells have cytoplasmic granules similar to normal LGLs.

Front 34

Adult T-cell leukemia/lymphoma

Back 34

ATLL.
neoplasm of CD4+ cells infected by HTLV-1, a virus endemic in Japan and the Caribbean. Skin lesions, lymphadenopathy, peripheral blood lymphocytosis, hypercalcemia
-clover leaf and flower cells

Front 35

Sezory Syndrome

Back 35

Leukemia form of mycosis fungoides, a mature T-cell lymphoma that presents on skin (red, patchy). on a slide you see pockets of abscesses in the epidermis. cribriform nuclei. cells express CD3 (no CD4 or CD8)

Front 36

T-cell chronic lymphoid leukemias

Back 36

-T-cell prolymphocytic leukemia (T-PLL)
-T-cell large granular lymphocyte leukemia
-Adult T-cell leukemia/lymphoma (ATLL)
-Sezory Syndrome

Front 37

Too little coagulation- causes

Back 37

1)Genetic disorders (Hemophilia, Von WIllebrand Disease)
2)Acquired disorders- decubitus ulcers (bed sores)
The deeper it is the bigger the bleeding realm
3)Trauma/ surgery
A lot of bleeding, slow clotting
Some drugs during surgery can cause anticoagulation

Front 38

other abnormal blood coagulation conditions

Back 38

-Too much coagulation
-Presence of clots- already there that create problems

Front 39

Drugs to help clotting

Back 39

*

Front 40

Fresh blood and plasma

Back 40

Replacement and supplement

Front 41

Factor VIII

Back 41

Produced by recombinant DNA technology and can be derived as a precipitate of plasma
8-12 hour half life- may need to be given multiple times depending on individual
Use: Hemophilia A

Front 42

Favor IX

Back 42

-Produced by recombinant DNA and purified human factor
-Heat treating reduces disease transmission
Use: Hemophilia B

Front 43

Vitamin K

Back 43

Factors dependent on it- II, VII, IX, X
Helps in the clotting cascade to enable clot formation

Front 44

Thrombin

Back 44

Obtained from bovine plasma and can be used topically as a powder
Activates platelets and convert factors V and VII to their active forms
Use: arrest minor bleeding or oozing
burns where skin isn’t there but oozing from subdermal layers

Front 45

Absorbable Gelatin (GELFOAM)

Back 45

Denatured collagen that is available as a sponge or powder
Sponge- looks like small piece of firm styrofoam
Non- antigenic- no immune response to it
Exposed collagen stimulates clotting, so using GELFOAM is helping this occur (because it is collagen)
This remains in place because if removed bleeding will occur again.
Eventually the collagen is broken down and absorbed by body, therefore not interfering with clot
Surgery or trauma

Front 46

Unwanted effects of coagulating agents

Back 46

Blood related agents- blood, plasma, Factors VII and IX
Can all carry viral infections
Hepatitis, AIDS, etc.

Front 47

Anticoagulant agents
Injectable

Back 47

for Unwanted coagulation a.Thrombo-embolic diseases
b.Extracorporeal devices- ie: renal dialysis
c.Prophylactic treatment

Front 48

Heparin

Back 48

Injection (SC or IV) NOT IM b/c of hematoma at site
Potentiates antithrombin- this inactivates thrombin
Side effects: unwanted bleeding if too much heparin- mucus membranes, open wounds, intracranial, gastro- intestinal
In vivo use:
To prevent deep vein thrombosis, pulmonary embolism, arterial thrombosis
In vitro use:
Hemodialysis, indwelling vascular catheters, laboratory blood samples
Heparinized saline used to prevent indwelling catheters from clotting
Antagonist for heparin:
Protamine sulfate

Front 49

Lepirudin (REFLUDAN) IV

Back 49

MOA: highly specific direct irreversible inhibition of thrombin
Use: when heparins are contra- indicated because of heparin induced thrombocytopenia (HIT)
Side effects:
Hemorrhage can occur at any site
Unexpected fall in hemoglobin and/ or blood pressure- hint that they are bleeding somewhere
Closely monitor the aPTT to make sure the proper amount is being administered

Front 50

Bivaliruden (ANGIOMAX) IV

Back 50

Mechanism: reversible and specific direct thrombin inhibitor
Has a rapid on and off set (when IV is stopped, so will the drug’s actions)
Inhibits platelet activation
Use; percutaneous coronary angioplasty
Side Effects:
Hemorrhage at any site
Most of the bleeding occurs at the site of the arterial puncture

Front 51

Argatroban IV

Back 51

MOA: direct thrombin inhibition- both free and clot associated
Inhibition of thrombin catalyzed or induced reactions
Ie: where thrombin is involved (fibrin formation, activation of Factors V, VIII, XIII)
c.Inhibition of activation of protein C
d.Inhibition of platelet aggregation
e.Reversibly binds to the thrombin active site
f.Does not require the co- factor anti- thrombin III for activity
3. Rapid elimination: T ½ 39-51 minutes
4. Use: Patients who have HIT
Side effects:
a.Hemorrhage can occur at any site
b.Intracranial hemorrhage has been observed

Front 52

Oral Agents

Back 52

*

Front 53

Warfarin

Back 53

Antagonist of Vitamin K
Decreases production of Factors II, VII, IX, X
There is tight range between therapeutic and lethal dose
Need close monitoring of levels, monthly
Side Effects: unwanted bleeding (same as for heparin)

Front 54

Remember NSAIDS lecture, those drugs compete for binding with

Back 54

Warfarin

Front 55

Centrum silver

Back 55

full dose of Vitamin K-can counteract Coumadin (vitamin K is the antagonist of Coumadin/warfarin)

Front 56

Factors that decrease effect of warfarin

Back 56

Enzyme induction-this would mean we are metabolizing warfarin faster
Increased production of clotting factors
-Increased vitamin K absorption
-Vitamins, or diet
-Inhibition of biotransformation

Front 57

Increase effect of warfarin

Back 57

-Decrease vitamin K absorption
Ie: if someone was taking Centrum silver and switched (ie: loss intake of Vitamin K)
-Displacement from plasma proteins- like in NSAIDS
Inhibition of platelet aggregation
Ie: Aspirin
-Decreased production of clotting factors

Front 58

Dabigatran etexilate

Back 58

In US trials, approved in Europe
Soon to be approved in US
MOA: binds to and inhibits thrombin (direct thrombin inhibitor)
Use: Prevent venous thromboembolic events in adults following total hip or total knee replacement surgery
Very specific approval
Study showed benefits over warfarin for atrial fibrillation patients

Front 59

Antiplatelet Agents

Back 59

*

Front 60

Aspirin

Back 60

MOA: irreversible inhibition of cyclooxygenase
Decreases eicosanoids- Thromboxane A2
Effect lasts the life of the platelet (approx. 7-10 days)
Because they do not have the ability to produce more cyclooxygenase
Aspirin therapy is typically a baby aspirin, 81 mg

Front 61

Clopidogrel (Plavix)

Back 61

MOA: irreversible block (irreversible covalent binding) of the ADP receptor on platelets
Inhibits ADP- induced binding of fibrinogen to platelet
Use: cardiovascular conditions that are prone to clot formation
Ie: many different kinds
Side effects: “not nice”, thrombocytopenic purpura (TTP)

Front 62

Ticlopidine (TICLID)

Back 62

Been around longer than clopidogrel
MOA: inhibits platelet function by inducing a thrombasthenia- like state
Irreversibly inhibits ADP- induced platelet- fibrinogen binding so, no platelet- platelet interactions
Same as clopidogrel
Use: mainly restricted to the treatment of ACUTE cerebral ischemia
Side effects: bleeding, nausea, diarrhea (10%), severe neutropenia in 1% of population

Front 63

Prasugrel (EFFIENT)

Back 63

MOA: inhibits PLATELET activation and aggregation mediated by the P2Y12 ADP receptor
Use: Prevents clots in patients undergoing angioplasty
Side effects: can cause significant, sometimes fatal bleeding; TTP has been reported

Front 64

Ticagrelor (BRILINTA)

Back 64

MOA: reversible antagonist of P2Y12 ADP receptor
Does not require bioactivation= faster onset
Use: cardiovascular conditions prone to clot formation
Side effects: difficulty breathing, heart rhythm abnormalities, major bleeding- same as other agents, minor bleeding- slightly higher than other agents

Front 65

Dipyridamole (PERSANTINE)

Back 65

MOA: increases cellular concentration of cyclic AMP in platelets (inhibits phosphodiesterase)
Ie: decreases breakdown of cyclic AMP
Alone has little or no effect
Used in combination with warfarin for prophylaxis of thromboemboli for prosthetic heart valves

Front 66

Prostacyclin (PGI2)

Back 66

MOA: increases intraplatelet cyclic AMP (stimulates adenylate cyclase)
Ie: increases synthesis of cyclic AMP
Blocks platelet adhesion and aggregation
**HINT** Platelet aggregation is associated with a decrease in platelet camp so, an increase in camp inhibits platelet adhesion and aggregation

Front 67

Specific Thrombolytic Agents

Back 67

*

Front 68

Streptokinase (STREPTASE)

Back 68

Protein from streptococci
MOA: complexes with plasminogen and causes conformational change, activating free plasminogen to plasmin
Produces systemic plasminogen activation- not clot specific

Front 69

Urokinase (ABBOKINASE)

Back 69

From human urine or kidney cells
MOA: cleaves arg-arg 560-561 peptide bond in plasminogen which activates it to plasmin
Produces system plasminogen activation- not clot specific
Typically used in cerebral vascular accident- CVA- if the stroke was caused by a clot and not a hemorrhage
There is a three hour window of time from onset of symptoms to administer these agents

Front 70

Tissue plasminogen activator, t-PA (ACTIVASE)

Back 70

MOA: binds to fibrin and activates bound plasminogen; cleaves arg- arg- 560-561 bond of fibrin- BOUND plasminogen
Inefficient at activating free systemic plasminogen- CLOT SPECIFIC

Front 71

Anisoylated plasminogen streptokinase activator complex (APSAC)

Back 71

MOA: prevents proteolytic activity of plasminogen; acetylated at the active site of plasminogen, therefore blocking its activity

Front 72

Antifibrinolytic Agent

Back 72

*

Front 73

Aminocaproid acid (AMICAR)

Back 73

MOA: binds to lysine binding sites on plasminogen and plasmin
Blocks the binding of plasmin to target fibrin
Potent inhibitor of fibrinolysis
ii. Oral or IV
iii. Can reverse excessive fibrinolysis but CANNOT LYSE NEW THROMBI
Side effect: myopathy, muscle necrosis