H&o: Myeloproliferative Diz

Front 1

What is the exact opposite of anemia?

Back 1

Erythrocytosis

Front 2

What is the definition of Erythrocytosis? Another quasi-name?

What are the two classifications of causes?

Back 2

An increase in the number of circulating RBCs per volume of blood.
Synonym = polycythemia

Primary, Secondary

Front 3

What causes Secondary Erythrocytosis?

Back 3

tissue hypoxia --> EPO production by the kidney

Front 4

Can treatment with EPO and/or androgens cause pirmary or secondary erythrocytosis?

Back 4

secondary

Front 5

What is hyperviscosity syndrome? This is developed by some patients with...

Back 5

Headaches
Visual changes
Tinnitus
Dizziness
Paresthesias
Decreased mental acuity

...erythrocytosis.

Front 6

What does the decision to treat secondary erythrocytosis depend on?

Back 6

prescence of hyperviscosity syndrome. yes = treat, no = don't treat.

Front 7

Define/Characterize the myeloproliferative disorders. Are they clonal or non clonal?

Back 7

Stem Cell Disorders leading to autonomous production of hematopoietic cells from ALL THREE LINEAGES (red cells, white cells, platelets)?

Clonal.

Front 8

Name the neoplastic disorder arising from a pluripotent stem cell, generally characterized by erythrocytosis, with or without concomitant thrombocytosis and leukocytosis.

Is this an example of primary or secondary erythrocytosis?

Back 8

Polycythemia vera.

primary.

Front 9

Primary vs. Secondary Erythrocytosis?

Back 9

Primary: BM is doin' whatever it wants.

Secondary: BM is doing what it's told.

Front 10

In P. vera, many if not all of the circulating blood cells are derived from a ______ neoplastic stem cell? Why is this?

Back 10

single

They can divide w/o EPO.

Front 11

How do we Dx. P. vera these days?

Back 11

We do two tests:
EPO = it will be low.

JAK2 mutation

Front 12

Will EPO be low or high in p. vera?

Back 12

low.

Front 13

JAK2 V617F causes loss of _______ leading to _____ ____ of JAK 2.

Is this seen in normal people?

Back 13

auto-inhibition

constitutive activation

Never.

Front 14

What the 4 phases of the progression of P vera?

Back 14

Latent phase - asymptomatic

Proliferative phase - pts may be hypermetabolic or have sx of hyperviscosity or thrombosis

Spent phase - anemia, leukopenia, secondary myelofibrosis, increasing liver and spleen size

Secondary AML
1-2% of pts treated with phlebotomy alone
Certain drug therapies increase risk

Front 15

What is the 'spent' phase of P vera?

Back 15

patients have anemia, thrombocytopenia
liver enlarged, splenomegaly.

Marrow is filled with scar tisue, liver and spleen start showing hematopoesis.

Front 16

What are 6 Sx more specific to P vera and myeloproliferative diseases?

* note that all of the other erythrocytosis sympt still apply in addition.

Back 16

Pruritis after bathing
Erythromelalgia
Hypermetabolic symptoms
Thrombosis (arterial or venous)
Hemorrhage

Front 17

What is Erythromelalgia?

Back 17

platets produced are too active

Front 18

PEx findings in P vera?

Lab values?

Back 18

Facial Plethora
Splenomegaly
Hepatomegaly
Distention of Retinal veins.

elevated platelets,
basophilia (can be seen in any MPD)
LOW EPO lvls
+ JAK2 V617F

elevated uric acid, elevated B12
elevated leukocyte alkaline phosphatase

Front 19

P vera Tx?

What has shown to decrease risk of thrombosis in PV patients?

Back 19

Phlebotomy until they're iron deficient.

Hydroxyurea

Low dose aspirin, give it to all patients.

Front 20

What are the downsides of treating P vera w/ phlebotomy?

Back 20

Increased risk of thrombosis

No effect on progression to spent phase

May be insufficient to control disease

Front 21

What is the wimpier sibiling of P.vera?

What % is clonal?

Those that aren't clonal, explain?

Back 21

ET: essential thrombocythemia

50%

the rest have polyclonal increase in megakaryocytes

Front 22

How do we make the Dx of essential thrombocythemia (ET)?

Back 22

First, rule out secondary causes of thrombocytosis: cancer, infection, inflammation, bleeding, iron deficiency

Exclude P vera
Exclude CML

Platelets must be >600 on two separate occasions

Front 23

Does ET progress to AML? What is the major complication of ET?

Can ET progress to myelofibrosis?

Back 23

No, rarely.

thrombosis.

Yes, it can.

Front 24

Thrombosis in ET is mainly which type?

Back 24

You see both arterial and venous.

Front 25

Labs in essential thrombocythemia (ET)?

Which percentage have a JAK2 mutation?

Back 25

If the plt count is very high, there may be pseudohyperkalemia and pseudohypoglycemia. This goes away if the blood is drawn into a heparinized tube.

50%.

Front 26

What is the Dx if patients have a + JAK 2 and high platelets?

Back 26

ET is the Dx

Front 27

What are pseudohyperkalemia and pseudohypoglycemia? when is this seen?

Back 27

platetes eat the sugar in the tubes where there is no heparin... can make the potassium & glucose artifically high.

Front 28

What is this?

Back 28

A giant platelet.

Front 29

What are these? When are they seen?

Back 29

abnormal megakaryocytes, ET.

Front 30

ET Tx? Who do we Tx?

How do we tx?

Back 30

Treatment targeted at reducing the platelet count

those who have had or are at risk for thrombosis, those >65 y.o., or pts with plts > 1-1.5 million

Anagrelide
Hydroxyurea
Interferon alpha

Front 31

In Myelofibrosis (MF), why can't the patients eat even though they're hungry?

Back 31

Spleen is HUuuuuGE, 'n takes up the space.

Hepatomegaly too.

Front 32

MF peripheral smear shows....

Back 32

leukoerythroblastic picture, with teardrops, NRBC and early granulocytes

Front 33

"Dry tap" is what? associated with what?

What is seen on BM biopsy?

Back 33

inability to aspirate liquid marrow

MF

Increased collagen and reticuluin

Front 34

What is the Tx of MF?

Is splenectomy a good idea?

Back 34

There is no definitive therapy

If patient is young, BM transplant can be done, but older patients have too high mortality

well, it's very risky., frequent complications of thrombosis, hemorrhage, and infection.

Front 35

What does 'myelo-' mean?

Back 35

marrow

Front 36

Define myelodysplastic syndromes.

Back 36

Conditions in which there is disordered maturation in 1 or more cell lines, usually producing cytopenias
Population of dysplastic cells represent an abnormal clone of cells

Front 37

Myelodysplastic syndromes are a ____ of disorders. Are they inherently progressive?

Back 37

spectrum

No.

Front 38

Are myelodysplastic syndromes (MDS) a disease of the old or the young?

Back 38

elderly.

Front 39

What are the lab findings in MDS?

Back 39

Macrocytosis w/o low B12 or folate

neutrophils can be hypogranular or bi-lobed

can have monocytosis (don't know why)

Front 40

How should we think about MDS?

Back 40

zerox, or a zerox, of a zerox.... and eventually (when you're old) you can't tell a c from an a, etc.

In the case of MDS, we have cells, but they're not quite right.

Front 41

What are some features of the marrow in MDS?

Back 41

Megaloblastic erythropoeisis

Ringed sideroblasts

Abnormal nucleus of RBC precursors (dyserythropoiesis)
Small megakaryocytes with abnormally hypolobate nuclei
Blast cells should account for <20% of marrow cells

Front 42

In which disorder should blast cells account for <20%?

>20%?

Back 42

MDS.

Acute leukemia.

Front 43

Where are ringed sideroblast seen?

Back 43

in MDS.

Front 44

___ - - - progression ---- -- -- > Acute Leukemia?

Back 44

MDS

Front 45

Tx of MDS?

Once the patient develops AML, the chacnes of achieving remission is _____, and their duration of any remission is ______.

Back 45

usually supportive: transfustions of RBCs and platelets, Growth Factors

decreased, shorter.

Front 46

If you're gonna get AML, whould you rather get it as a young person de novo, or as an old person as the end of a progression of MDS? Why?

Back 46

young person, because they kid's other stem cells are probably ok. those old people with progressive MDS probably have corrupted their other cells as well.

Front 47

What is a clonal stem cell disorder that affects primarily megakaryocytes?

Back 47

Myelofibrosis (MF)

Front 48

The spent phase of all myeloproliferative disorders can be difficult to distinguish from...

Back 48

...primary MF

Front 49

What type of cell is shown here? What is it characteristic of and why?

Back 49

Ringed sideroblast. Myelodysplastic Syndrome (MDS).
The body has iron available but cannot incorporate it into hemoglobin.