Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Path - Haem > Polycythaemia and myeloproliferative disorders > Flashcards

Polycythaemia and myeloproliferative disorders Flashcards

1
Q

what is PV and what is the MOA behind it?

A

PV: overproduction of BLOOD CELLS of the haematopoeitic stem cell lineage (rbc, platelet, and wbc - the dominating cell linee in PV will be rbc)

EPO normally binds to the stem cells and activates = blood cells made

JAK2 defect (Janus kinase 2) affects the haematopoeitic stem cells meaning they are always active - even without EPO binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what are the phases of PV?

A

“poly phase” - overproduction of cells

spent phase - when the cells take up the bone marrow volume - hypercellular resulting in cytopaenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what would ivx show in PV? (basic outline)

A

Bloods:
Increased Hb
Increased Haematocrit
Increased platelet and WCC

EPO levels - low may be high (2ndary)

+- Bone marrow biopsy: fibrosis

Mutation testing: V617F mutation -> JAK 2 defect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

give some examples of myeloproliferative neoplasms ?

A

Myeloid lineage cell prolifration:

BCR-ABL positive:
CML

BCR-ABL negative:
Polycythaemia vera
Primary Myelofibrosis
Essential thrombocytosis

the above 3 are the mpf disorders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

myeloproliferative disorders have risk of progression to what?

A

AML (not ALL as is from myeloid line)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

how does one tell the difference between True and relative Polycythemia?

A

Relative - plasma volume is decreased giving the impression that RBC conc has increased when it hasn’t.

true - rbc conc has increased

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

list some causes of relative polycythemia

A

Alcohol
obesity
diuretics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

when isotope dilution studies reveal true polycythaemia, what are the possible causes?

A

Primary polycythemia vera (reduced EPO)

Secondary Polycythaemia (elevated EPO)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

list some causes of True secondary polycythemia

A

Is Non malignant condition

Appropriate:
High altitude
Hypoxic lung disease
Cyanotic heart disease
High affinity haemoglobin

Inappropriate:
Renal disease (cysts, tumours inflammation)
uterine myoma
other tumours (liver, lung)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is the result of the V617F Mutation?

A

Activating Tyrosine kinase mutation:

expansion increase in MATURE/end cells not blasts:

Red cells; polycythaemia
Platelets; essential thrombocythaemia
Granulocytes; chronic myeloid leukaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

which genes are responsible in the MPD?

A

PV - JAK2 V61F 100%

ET - Jak2 60%, Calreticulin 30%, MPL 5%

PMF - Jak2 60%, Calreticulin 30%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is EPO level in polycythaemia?

A

Primary - low EPO

Secondary - high EPO

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the clinical presentation of PV? what will be the clnical findings ?

A

Symptoms of increased hyper viscosity:
Headaches, light-headedness, stroke
Visual disturbances
Fatigue, dyspnoea

Increased histamine release:
Aquagenic pruritus - itching post hot shower
Peptic ulceration

Clinical findings:
 Erythromelalgia: red painful extremeties
 Thrombosis
 Retinal vein engorgement
 Gout due to increased red cell turnover and
overproduction of uric acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what is the rx for PV?

A

Aim to reduce HCT : target HCT <45%
Venesection
Cytoreductive therapy - Hydroxycarbamide

Aim to reduce risks of thrombosis:
Control HCT
Aspirin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Sustained thrombocytosis >600x109/L

is indicated of?

A

ET

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the clinical presentation of PV?

A

Incidental finding on FBC (50% cases)
Thrombosis: arterial or venous
CVA, gangrene, TIA
DVT or PE

Bleeding: mucous membrane and cutaneous (because not a clotting fx issue)

Headaches, dizziness visual disturbances
Splenomegaly (modest)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is the rx for ET?

A

Aspirin: to prevent thrombosis

Anagrelide: specific inhibition of platelet formation, side effects include palpitations and flushing

Hydroxycarbamide: antimetabolite. Suppression of other cells as well.

Alpha interferon - can be used if under 40

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

how does Primary Myelofibrosis present?

A

Incidental in 30%

Presentations related to:
Cytopenias: anaemia or thrombocytopenia
Thrombocytosis
Splenomegaly: may be massive
  - Budd-Chiari syndrome

Hepatomegaly

Hypermetabolic state:

  • Weight loss
  • Fatigue and dyspnoea
  • Night sweats
  • Hyperuricaemia (= GOUT)
19
Q

the following Haematological findings are consistent with which condition

Leucoerythroblastic picture
Tear drop poikilocytes
Giant platelets
Circulating megakaryocytes

Extramedullary haemopoiesis and enlargement in spleen and liver and

A

Primary Myelofibrosis

- arer 2 pahses prerfibrotic and fibrotic - no hepatosplenomegaly in prefibrotic

20
Q

what are the findings on ivx for PM?

A
  1. Blood film
  2. Bone marrow - (must always, not optional):

‘Dry tap’ (Hypercellular marrow in prefibrotic stage)

Trephine biopsy:
Increased reticulin or collagen fibrosis
Prominent megakaryocyte hyperplasia and clustering with abnormalities
New bone formation
Osteosclerosis - hardening and increased density

  1. DNA : JAK2 or CALR mutation
21
Q

what is the rx for PM?

A
  1. Supportive: RBC and platelet transfusion often ineffective because of splenomegaly
  2. Cytoreductive therapy: hydroxycarbamide (for thrombocytosis, may worsen anaemia)

High prognostiic score/poor surival chance:

  1. Ruxolotinib: JAK2 inhibitor
  2. Allogeneic SCT (potentially curative)
  3. Splenectomy for symptomatic relief: hazardous and often followed by worsening of condition
22
Q

which cell does CML Chronic myeloid leukaemia arise from?

A

CML is one of the Myeloprolifive disorders that arises from an abnormal pluripotent BM stem cell

23
Q

what would ivx findings reveal for CML?

A

Exam
Massive splenomegaly +/- hepatomegaly

FBC
Hb and platelets well preserved or raised
Massive leucocytosis 50-200x109/L

Blood film:
1. Bi-phasic peak of Neutrophils AND myelocytes
(not blasts if chronic phase - infact v few blasts present)
2. Basophilia

Platelet count raised/upper normal

24
Q

what are the presenting sx of CML?

A

Lethargy/ hypermetabolism/ thrombotic event : monocular blindness CVA, bruising bleeding

25
Q

what drives myeloid proliferation in CML?

A

BCR ABL fusion gene expresses a fusion oncoprotein with constitutive tyrosine kinase activity.

26
Q

how can monitoring of response to therapy occur in CML? what is the ideal response?

A

RT-PCR of BCR-ABL fusion transcript for diagnosis BUT

  1. quantify with RQ-PCR to determine response to therapy
  2. FBC (leucocytosis)
  3. Cytogenetics (FISH: bcr-abl gene % presence)

ideal response - at 1 year:
0% cells with BCL-ABR (otherwise inc risk recurrence)
0% blasts
Normal WCC

27
Q

what are the phases of CML? what are their lengths?

A

CAB

Chronic phase: Median 3-4 years duration

Advanced phases:

  1. Accelerated phase (10-19% blasts) - up to 1 year
    ( presence of basophilia)
  2. Blast crisis (>20% blasts) - Median survival 3–6 months refractory to rx
28
Q

what kind of drug is imatinib?

A

Abl Tyrosine Kinase inhibitor

29
Q

Which are the most sensitive ways of detecting disease in CML?

A

Molecular most sensitive - BCR-ABL transcripts

Followed by cytogenetic analysis - the FISH metaphase/interphase BCR-ABL:

 - Partial 1-35% Philadelphia positive 
 - Complete 0% Ph positive

Haematological response
- Complete Haematological Response WBC<10x109/l

30
Q

in the treatment of CML, which TKIs should be used?

A

Commence on oral TKI 1st generation

Failure (1) > switch to 2Gen or 3G TKI
- if No complete cytogenetic response @ 1year

Failure (2) > consider allogeneic SCT
- If progression to accelerated or blast phase

Imatinib (1Gen,) Dasatanib Nilotonib (2G) Bosutinib (3G)

31
Q

case 3 + the notes i made on it is quite good for consolidation.

A

okay

32
Q

what other conditions can imatinib be used for?

A

ALL - anything with BCR-ABL gene

33
Q

what is An important initial goal of treatment CML?

A

to achieve a complete cytogenetic response (0% cells with bcr abl):

a patient no longer has evidence of cells with the Philadelphia chromosome in the bone marrow and has normal levels of blood cells

34
Q

what is The most sensitive test to look for remaining CML ?

A

a quantitative reverse transcriptase PCR (Q-RT-PCR) test.

35
Q

if a patient continues taking the medication - eg Imatinib as directed and the results of this test begin to rise, what does this mean?

A

the current treatment is no longer working. sometimes, a TKI stops working because the CML develops resistance to it

36
Q

which therapy is started at what phase in leukaemia? which stage is Imatinib most effective?

A

Chronic phase - imatinib most effective here. Allo SCT if drugs dont work

Accelerated phase - can use 2nd/3rd gen TKI. best todo Allo SCT

Blast phase - 2nd/3rd gen + chemo (wont cure). hydroxyurea.

37
Q

what is JAK2 and its role in the control of haematopoesis?

A

are tyrosine kinases bound to the haemopoeitic cell growth factor receptors - HCGFR

become phosphorylated (by ATP) when growth factors bind to receptor

leads to activation of the STAT pathway (PI3K, ERK etc) ultimately leading to cell proliferation

38
Q

which are the constitutionally active JAKs?

A

Mutated ones:

JAK2 V617F
JAK2 Exon 12

39
Q

what is the chief diagnostic ivx in PV?

A

JAK 2 V617F mutation present (diagnostic)

40
Q

what do the following mutations cause:

JAK2 V617F
JAK2 Exon 12

A

JAK2 V617F - polycythaemia vera

JAK2 Exon 12 - primary erythrocytosis

41
Q

what is the old Diagnostic criteria in PV? (detailed)

A 
Raised RCM (red cell mass) >25% of mean normal predicted value
 Hb >18.5g/dL in men >16.5g/dL in women

 BM histology:
■ Increased cellularity
■ Megakaryocytic abnormalities
■ Variable increase in reticulin fibres

then there are other thigns that would confirm but are not diagnostic. Curernt criteria:

Increased red cell production and usually also increased platelets and sometimes neuutrophils
 Most patients will have the JAK2 V617F mutation

42
Q

which myeloproliferative disorder affects women more?

A

Essential thrombocytosis

Females : males equal first peak (30y/o) but females predominate second peak (55years +)

43
Q

which condition is associated with reactive bone marrow fibrosis and extramedullary haematopoieisis?

A

Chronic idiopathic myelofibrosis / P Myelofibrosis

44
Q

what is the rx in myelofibrosis?

A

Blood transfusions

Splenectomy

Thalidomide with or without prednisolone

hydroxycarbamide for thrombocytosis

Path - Haem (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions