99 - Polycythemia Vera Flashcards
What are the two groups of chronic myeloproliferative diseases?
- Myeloid phenotype
2. Megakaryocyte/erythroid hyperplasia
What are the three myeloid phenotype causing myeloproliferative diseases?
- CML (myelocytic- BCR-ABL)
- CNL (neutrophilic)
- CEL (eosinophilic)
What are the three Megakaryocyte/erythroid hyperplasia causing myeloproliferative diseases?
- PV (polycythemia vera)
- ET (essential thrombocytosis)
- PMF (primary myelofibrosis)
PV frequency increases with ____, it has a slight ____ tendency, with ____ being more prominent in sporadic cases
Age
Familial
Female
In ___ of patients we can find known chromosomal mutations such as ____ deletion or ____
30%
13q or 20q
9 trisomy
In ___ we can find ____ mutation where____ replaces ____
95%
JAK2
Phenylalanine
Valine
The mutation in JAK2 activates it without ___ dependency leading to an uncontrolled cell productio
EPO
Clinical features of PV include: (4)
Leukocytosis/Thrombocytosis
Splenomegaly
Thrombus (venous/arterial)
Aquagenic pruritus
Hypervascular erythrocytosis may lead to the following symptoms: (2)
- Systolic HTN
2. Neurological symptoms (vertigo, headache, visual impairment, TIA, tinnitus)
Thrombocytosis may lead to the following symptoms: (4)
- Thrombosis (cerebral, GI, hepatic vein)
- Acquired vWF
- Erythromelalgia
- Bleeding disorders (fingers ischemia, etc..)
What is the approach to diagnosing patients with PV?
*Increased hct/Hgb?
yes? continue
- Measure RBC mass
normal- Relative erythrocytosis
elevated- continue
*Measure serum EPO levels-
low- PV- confirm with JAK2 mutation
elevated- continue
*Measure arterial O2 saturation
low- DD (COPD, high altitude, AV shunt…)
normal? continue
*Smoker?
no?- measure hemoglobin affinity-
increased- O2 affinity hemoglobinopathy
normal- search for tumors (renal US/CT)
yes?- Measure carboxyhemoglobin
elevated? Smokers polycythemia
In order to confirm absolute erythrocytosis by measuring _____. When unavailable and O2 saturation is normal- check for ____
RBC mass
JAK2 mutation
Normal EPO does not disclose ___, but high EPO suggests ____
PV
Secondary erythrocytosis
What are the 3 situations leading to microcytic erythrocytosis (check RDW and MCV)?
- Beta thalassemia (normal RDW)
- Hypoxic erythrocytosis ( wide RDW)
- PV (wide RDW due to iron deficiency)
___ examination has no value when trying to diagnose PV
BM
The lack of ____ does not rule out PV
genetic marker
What are the two mechanisms leading to PV complications?
Hyperviscosity- due to increased amount of cells
Increased cell turnover- increase in cytokines and uric acid
_____ infection is more common in PV patients, which may lead to higher frequency of ____
H. Pylori
PUD
Men with PV should aim for Hgb of ___ and hct of ___, in order to avoid thrombosis.
<14
<45%
Women with PV should aim for Hgb of ___ and hct of ___, in order to avoid thrombosis.
<12
< 42%
What are the 3 main treatments of PV?
- Phlebotomy
- Anticoagulation
- Ruxolitinib
In PV patients, phlebotomy is recommended once every ___ months
3
If treating PV with anticoagulation, we must avoid ____ when ____ is not under control
Salicylates
RBC
Ruxolitinib is ____, and is used in PV patients who also suffer from ___ or ____.
JAK2 inhibitor
Myelofibrosis
Myeloid metaplasia
Asymptomatic _____ (<10) does not require treatment, unless the patient is to be treated with ____. If so, treat with _____
Hyperuricemia
Chemotherapy
Allopurinol
How would you treat symptomatic splenomegaly?
- IFN alpha (reduce JAK2 levels)
2. PDE inhibitor/hydroxyurea
Why PDE inhibitor is preferred over hydroxyurea when treating PV with symptomatic splenomegaly?
PDE inhibitor is not toxic for the BM, and protects from thrombosis
If PV patient is resistant to hydroxyurea how will you continue?
Ruxolitinib
If PV patient is resistant to Ruxolitinib how will you continue?
Splenectomy
What is PMF?
Primary myelofibrosis is a clonal hematopoietic stem cell disorder associated with mutations in JAK2, MPL or CALR and characterized by marrow fibrosis, extramedullary hematopoiesis, and splenomegaly
___ are more likely to be diagnosed with PMF, usually in their ___decade of life
Men
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