Heme-Onc Iannuzzi

Front 1

What drives platelet aggregation and what pushes against this?

Back 1

Platelets---> thromboxane A2 --> increase adenylate cyclcase --> increase cAMP to activate more platelets.

Endothelial cells --> prostacyclin --> decrease adenylate cyclase

Front 2

How is platelet-platelet aggregation mediated?

What drug(s) will inhibit this?

Back 2

ADPr bound --> expression of GP IIb/IIIa --> fibrinogen binds these receptors together.

Hint 2

Clopidogrel / ticlopidine antagonize the ADPr.

Adciximab inhibits the GP IIb/IIIa component.

Front 3

How is platelet-collagen aggregation mediated?

Back 3

Platelets express GP Ib that binds vWF and vWF binds the subendothelial collagen.

Front 4

Which factors depend on Vit K and how are they activated?

Back 4

Inactive VitK -- epoxide reductase --> active vitK --> activation of II, VII, IX, X, and C and S

Front 5

What do proteins C and S do and how?

Back 5

Protein C is activated by thrombomodulin in the presence of cofactor protein S. Then protein C cleaves and inactivates Va and VIIIa.

Front 6

How does factor V Leiden mutation affect thrombolysis?

Back 6

Factor V Leiden is a mutated factor V that is resistant to inactivation by active protein C ---> formation of clots.

Front 7

How does heparin participate in coagulation?

Back 7

Heparin activates antithrombin --> inactivates II, VII, IX, X, XI

Front 8

What does the PT test? The PTT? TT?

Back 8

PT - extrinsic pathway - VII and vWF

PTT - intrinsic pathway - TENET

TT - platelet function (not cascadE)

Front 9

What should you do with an abn PTT?

Back 9

Abn PTT --> repeat with 1:1 mixture with nl --> if still abn think inhibition (antiphospholipid as in SLE) and if normal now, then think deficiency of TENET

Front 10

What is tPA?

Back 10

tPA is used clinically as a thrombolytic. It activates plasmin from plasminogen in order to cleave the fibrin mesh.

Front 11

Bite cell

Back 11

G6PD deficiency - bite cell

Front 12

Helmet cell

Back 12

Helmet cell (schistocyte) - DIC, TTP/HUS, traumatic hemolysis

Front 13

Acanthocyte (spur cell)

Back 13

Liver dz, abetalipoproteinemia* - acanthocyte

Hint 13

Abetalipoproteinemia is a rare autosomal recessive disorder that interferes with the normal absorption of fat and fat-soluble vitamins from food. It is caused by a deficiency of apolipoprotein B-48 and B-100, which are used in the synthesis and exportation of chylomicrons and VLDL respectively.

Front 14

Basophilic stippling

Back 14

Thalessemias, AOCD, Iron def, Lead poisoning - basophilic stippling

Hint 14

Baste the TAIL (thal, AOCD, Iron def, Lead)

Front 15

Teardrop cell

Back 15

Bone marrow infiltration - teardrop cell

Front 16

Target cell

Back 16

Target cell - HbC dz and thalessemia

Hint 16

When you reach the target, HALT !

Front 17

Heinz body (what is pathophys)

Back 17

a-thalessemia, G6PD def - Heinz bodies

Hint 17

Oxidation of iron from ferrous to ferric form leads to denatured Hg precipitation and damage to RBC membrane. Leads to formation of bite cells.

Front 18

Howell-Jolly bodies (what is pathophys)

Back 18

functional asplenia - Howell-Jolly bodies

Hint 18

Basophilic nuclear remnants found in RBCs of Howell-Jolly bodies

Front 19

Patient has esophageal web and atrophic glossitis, what should you look for?

What is this called and what is the major worry?

Back 19

Plummer Vinson Syndrome (PVS)
Triad: atrophic glossitis, esophageal web and iron def anemia. Get ferritin, TIBC tests and peripheral blood smear.

Also, increased risk of esophageal cancer.

Front 20

What are the a-thal's and where are they present?

Back 20

a-thal (decreased syn)
4 gone - Hg Barts (gamma tetramer) and hydrops fetalis
3 gone - HgH (beta tetramers)
1 or 2 gene deletion - asymptomatic

Hint 20

a-thal's - prevalent in Asia (cis) and Africa (trans)

Front 21

What are the b-thals and who gets them?

Back 21

B-thal - point mutation in splicing sites and promoter sequences, seen in Mediterranean populations

Hint 21

B-thal minor (heterozygote)
- asymptomatic, some b-globin produced, high HbA2

B-thal major (homozygote)
- B chain is absent - severe anemia requiring transfusions (-> hemachromatosis)
- marrow expansion (crew cut skull x-ray)
-
HbS/b-thal - most common in US, mild to moderate sickling depending on b-globin production

Front 22

What kind of anemia does lead poisoning cause? How?

Back 22

Lead poisoning --> inh ferrochelatase and ALA dehydratase which decreases heme syn --> micorcytic hypochromatic anemia

Hint 22

Lead poisoning --> basophilic stippling (TAIL)

Front 23

What kind of anemia does sideroblastic anemia cause? How?

What is Tx?

Back 23

Sideroblastic anemia - X linked defect in gamma-aminolevulinic acid (ALA) synthase gene --> microcytic hypochromatic anemia

This most commonly caused by alcohol and can be caused by lead poisoning as well.

Hint 23

Tx sideroblastic anemia with pyridoxine (B6)

Front 24

What drugs can be associated with folate deficiency anemia?

Back 24

Folate deficiency: methotrexate, trimethoprim

Front 25

What is subacute combined neurologic degeneration?

Back 25

Subacute combined neurologic degeneration is seen in B12 (cobalamine) deficiency due to B12 involvement in the fatty acid pathways

Front 26

What drugs can cause a nonmegaloblastic macrocytic anemia?

Back 26

Nonmegaloblastic, macrocytic anemia:
- 5-FU
- AZT
- Hydroxyurea

Front 27

What serum markers are seen in AOCD?

Back 27

AOCD serum markers:
- Increased hepcidin --> decreased release of iron from macros --> decreased iron, decreased TIBC and increased ferritin

Front 28

What drugs can cause aplastic anemia?

What does the bone marrow look like?

Back 28

Aplastic anemia: (AABCC) alkylating agents, antimetabolites, benzene, carbamazepine, chloramphenicol

Hint 28

Aplastic anemia - fat infiltration of bone marrow, hypocellularity

Front 29

Increased RDW and increased MCHC

What are you thinking and how do you confirm?

Back 29

Increased MCHC think hereditary spherocytosis, a defect in RBC membrane skeleton component (ankryin, spectrin, band 3.1)

Hint 29

Confirm hereditary spherocytosis with osmotic fragility test.

Front 30

What can exacerbate G6PD def?

What is the pathophys?

Back 30

G6PD def exacerbations
- sulfa drugs, infections, fava beans, malarial drugs

--> hemolytic anemia

Hint 30

G6PD def --> decreased glutathione --> increased susceptibility of RBC to oxidative stress (thus they rupture) and Heinz bodies, bite cells are present on PBS

Front 31

Pyruvate kinase def

Back 31

Pyruvate kinase def
- AR disorder that leads to decreased ATP and RBC rigidity
- It presents as hemolytic anemia in a newborn

Front 32

What is the mutation in HbS?

Back 32

HbS - valine for glutamic acid at 6th aa of B-globin chain

Front 33

What is the problem in paroxysmal nocturnal hemoglobinuria (PNH)?

Back 33

PNH - decreased protective proteins on RBC membrane surface --> complement mediated RBC lysis

Front 34

What are warm and cold autoimmune hemolytic anemia?

Back 34

Warm - IgG - chronic anemia associated with SLE, CLL, a-methyldopa

Cold - IgM - acute anemia triggered by cold and seen with Mycopasma pneumonia and Mononucleosis

Front 35

What causes erythroblastosis fetalis?

Back 35

Erythroblastosis fetalis is due to Rh+ / Rh- interaction between mother and fetus

Front 36

How are the direct and indirect Coomb's tests performed?

Back 36

Direct - add anti-IgG to patients RBC's to test for surface IgG

Indirect - add normal RBCs to patients serum to test for circulating anti-RBC IgG

Front 37

What normally keeps glutathione reduced? Why is this needed?

What happens when this isn't working?

Back 37

NADPH usually keeps glutathione reduced using enzyme G6PD to achieve this. Reduced glutathione detoxifies free radicals and peroxides.

Hint 37

When NADPH is decreased in RBCs, hemolytic anemia results due to RBC damage by oxidizing agents.

Front 38

What enzymes are affected in lead poisoning, what accumulates in the blood and what symptoms does this cause?

Back 38

Lead poisoning --> ferrochelatase and ALA dehydratase are inh --> accumulation of protorphyrin

Hint 38

Lead poisoning Sx include mental deterioration in children and HA, memory loss and demyelination in adults.

Front 39

What enzymes are affected in acute intermittent porphyria, what accumulates in the blood and what symptoms does this cause?

How is it Tx?

Back 39

Acute intermittent porphyria --> porhobilinogen deaminase (aka uroporphyrinogen-I-synthase) which leads to accumulation porphobilinogen, delta-ALA and uroporphyrin.

Hint 39

Sx of acute intermittent porphyria include the 5 P's
- Painful abdomen
- Pink urine
- Polyneuropathy
- Psych disturbances
- Precipitated by drugs

Tx with glucose and heme which inh ALA synthase

Front 40

What are the Sx of LEAD poisoning? How is it Tx?

Back 40

LEAD
Lead Lines on gingivae and on epiphyses of long bones
Encephalopathy and Erythrocyte basophilic stippling
Abd colic and sideroblastic Anemia
Drops - wrist and foot

Hint 40

Tx with Dimercaprol / EDTA or succimer for kids.

Front 41

How are platelet count (PC) and bleed time (BT) affected by each of the following?
- GpIb deficiency
- GpIIb / IIIa deficiency
- ITP
- TTP

Back 41

GpIb deficiency (Bernard-Soulier dz) --> decreased PC and increased BT

GpIIb / IIIa (Glanzmann's thrombasthenia) --> nl PC and increased BT

Hint 41

ITP (anti-GpIIb/IIIa antiB's--> platelet destruction) --> decreased PC and increased BT

TTP (def of ADAMTS13 a vWF metalloprotease) --> decreased PT and increased BT

Front 42

How are PC, BT, PT and PTT affected by von Willebrand's dz?

How common is it?

Back 42

von Willebrand's dz:
nl PC, increased BT, nl PT and nl or increased PTT (vWF helps carry factor VIII)

Hint 42

von Willebrand's dz is a mild but most commonly inherited bleeding disorder (AD inheritance).

Front 43

What are 4 distinguishing characteristics between Hodgkin's and non-Hodgkin's lymphomas?

Back 43

Hodgkins:
- Reed-Sternburg cells
- Continuous spread
- B symptoms
- Associated with EBV (50%)

Hint 43

Non-Hodgkins:
- Majority involve B cells
- Non contiguous spread
- Fewer constitutional symptoms
- May be associated w/ HIV or immunosuppression

Front 44

What cell markers are present in the "Hodgkin's lymphoma cell"? How does this cell's presence correlate to prognosis?

Back 44

Hodgkin's lymphoma --> Reed-Sternburg cell --> CD 30+ and CD15+

- Lymphocyte / RS ration correlates to prognosis

Front 45

What is the most common form of Hodgkin's lymphoma? What is its prognosis?

Back 45

Nodular sclerosing is the most common form of Hodgkin's lymphoma. It has a good prognosis.

Front 46

What are the different forms of Hodgkin's lymphoma? Which has a poor prognosis?

Back 46

Hodgkin's lymphoma
1. Nodular sclerosis
2. Mixed cellularity
3. Lymphocyte predominant
4. Lymphocyte depleted *rare but poor prognosis*

Front 47

What are the different forms of non-Hodgkin's lymphoma?

Back 47

Non-Hodgkin's B-cell lymphomas
- Burkitt's
- Diffuse large B-cell
- Mantle cell
- Follicular

Non-Hodgkin's T-cell lymphomas
- Adult T-cell lymphoma
- Mycosis fungoides / Sezary syndrome

Front 48

Burkitt's Lymphoma

Who?
Genetics?
Etc (3)?

Back 48

Non-Hodgkin's B-cell lymphoma
- Adolescents/ young adutls
- t (8;14) c-myc gene next to heavy chain IgG
- "Starry sky" appearance, ass. w/ EBV, jaw lesion in endemic form in Africa and pelvic or abdomen lesion in sporadic form

Front 49

Diffuse large B-cell lymphoma

Who?
Genetics?
Etc (2)?

Back 49

Non-Hodgkin's B-cell lymphoma
- Mostly affects adults (20% children)
- no sign genetics
- Most common adult NHL
- 20% mature T cell in origin

Front 50

Patient has a "starry-sky" appearance on lymph aspirate. What is the dz? What is the genetics of this dz?

What are the two forms?

Back 50

Starry sky = Burkitt's lymphoma
- t (8;14) c-myc next to heavy-chain IgG
- ass. w/ EBV

Hint 50

Burkitt's lymphoma (ass. w/ EBV)
- Endemic (Africa) - jaw lesions
- Sporadic - pelvic/abd lesions

Front 51

Mantle cell lymphoma

Who?
Genetics?
Etc (2)?

Back 51

Mantle cell lymphoma:
Non-Hodgkin's B-cell lymphoma
- Older males
- t (11;14)
- CD5+
- Poor prognosis

Front 52

Follicular lymphoma

Who?
Genetics?
Etc (2)?

Back 52

Non-Hodgkin's B-cell lymphoma
- Adults
- t (14;18) bcl-2 expression
- Difficult to cure, indolent course
- bcl-2 inh apoptosis

Front 53

What are the two neoplasms of mature T-cells?

Who is affected by the T-cell neoplasms?

Back 53

Adult T-cell lymphoma - caused by HTLV-1, causes cutaneous lesions and has an aggressive course

Mycosis fungoides / Sezary syndrome - also causes cutaneous patches and nodules but has an indolent course

Hint 53

Both affect adults

Front 54

Match the genetic marker with the cancer and provide the gene.
- t (8;14)
- t (11;14)
- t (14;18)
- t (15;17)
- t (9;22)
- t (11;22)

Back 54

t (8;14) c-myc - Burkitt's

t (11;14) - Mantle cell

t (14;18) bcl-2 - follicular

- t (15;17) M3 type AML RAR-a

- t (9;22) CML bcr-abl Philadelphia chromosome

- t (11;22) Ewing's sarcoma

Front 55

What are the symptoms of multiple myeloma?

Back 55

- hyperCalcemia
- Renal insufficiency
- Anemia
- Bone / Back pain

Hint 55

CRAB

Front 56

What is the most common bone primary tumor of bone in the elderly? What does this tumor produce?

What signs are indicative of this dz?

Back 56

Multiple myeloma is most common bone primary tumor of bone in the elderly. It produces large amounts of IgG or IgA.

Hint 56

MM is associated with:
- Punched out lesions on Xray
- Monoclonal Ig spike (M protein)
- Ig light chains in urine (Bence Jones protein)
- Rouleaux formation on PBS

Front 57

How do you distinguish MM from Waldenstrom's?

Back 57

MM - IgG or IgA

Waldenstroms - IgM

Front 58

What leukemia affects children?

What markers are present in this dz?

What genetic abnormality is cause for hope (better prognosis)? What is the dz course like?

Back 58

ALL affects children
- TdT + (marker of pre-T and preB cells)
- CALLA +

Hint 58

ALL
t (12;21) = good prognosis

Can spread to CNS and testes, but very responsive to Tx.

Front 59

What age is affected by SLL or CLL?

What signs are indicative of SLL/CLL?

Back 59

SLL and CLL (CD5+) affect older adults (>60 yrs).

Hint 59

SLL / CLL is often asymptomatic, but:

- SLL and CLL --> smudge cells on PBS
- Warm antibody autoimmune hemolytic anemia

Front 60

What is Hairy Cell Leukemia? Who does it affect and how is it distinguished?

Back 60

Hairy cell leukemia is a mature B-cell tumor of the elderly. Cells have filamentous, hairlike projections.

Hint 60

Hair cell leukemia--> TRAP +
- Tartrate-resistant acid phosphatase

Front 61

Auer rods --> how do you treat?

Who is affected?

Back 61

Auer rods - AML M3 --> Tx with all-trans retinoic acid (vit A)

Hint 61

AML affects adults

Front 62

Patient presents with increased PMNs, metamyelocytes, basophils, splenomegaly and very low leukocyte alkaline phosphatase.

What genetics should you look for? What do they have?

How do you treat? What is the potential worry?

Back 62

CML - Philadelphia chromosome t (9;22) bcr-abl

Tx CML with imatinib (anti bcr-abl antibody)

Hint 62

CML and progress to AML or ALL (blast crisis)

Front 63

List the age groups for each:
ALL, AML, CML, CLL

Back 63

ALL < 15

AML med onset 60 yrs

CML 30-60

CLL > 60

Front 64

What is a leukemoid reaction?

Back 64

Leukemoid rxn - increase WBC (over 10,000) with left shift and increased leukocyte alk phosphatase

Front 65

What are peroxidase-positive cytoplasmic inclusions in granulocytes or myeloblasts?

How are they Tx and what might they cause when Tx?

Back 65

Auer rods - AML - Tx with all-trans retinoic acid

Tx can lead to release and DIC

Front 66

JAK2 mutations

Back 66

JAK2 is involved in hematopoietic growth factor signaling. Mutations are implicated in myeloproliferative disorders other than CML.

Hint 66

If Philadelphia chromosome is present this isn't.

Front 67

What is similar / diff between polycythemia vera and essential thrombocytosis?

Back 67

Polycythemia vera and essential thrombocytosis both involve abnormal clone of hematopoietic stem cells that are increasingly sensitive to growth factors (mut JAK2), but essential thrombocytosis is specific for megakaryocytes (increased platelets)