Term
| What are the major subsets of myeloproliferative disorders/neoplasms (MPD/MPN) |
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Definition
Clonal expansions of multi-potential hematopoietic progenitor cells where one cell type dominates.
1) Polycythemia vera; PV (Erythrocytes)
2) Chronic myeloid leukemia (Neutrophils)
3) Essential Thrombocythemia; ET (Platelets)
4) Primary Myelofibrosis (PMF) with fibrosis of marrow |
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Term
Patient presents with headache, chest pain and dyspnea.
They describe that they have been having serious episodes of itching following hot showers and burning foot pain.
On PE, you notice gout on their right toe and retinal hemorrhages, as well as moderate splenomegaly.
What do you expect to see on blood work and what is the pathophysiology of this condition? |
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Definition
Symptoms and Signs are consistent with Polycythemia vera
- Headache, chest pain and dyspnea fit Hypervolemia.
- Evidence of aquagenic pruritus is consistent, as is secondary gout
- Burning pain of feet (Erythromelalgia) is also consistent.
- Retinal hemorrhages and moderate splenomegaly fit as well.
1) Blood work should show elevated Hb (>18) and HCT (>55%)
- 40% of patients will have elevated WBC and 60% have elevated platelets
2) Mutation in JAK2 (cytoplasmic TK) that leads to auto-activation of cytokine receptors for erythropoiesis causing proliferation independent of EPO. |
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Term
Which of the following is NOT a common clinical finding associated with Polycythemia vera?
1) Moderate splenomegaly
2) Pruritis following hot showers
3) Erythromelagia of feet.
4) Fever
5) Thrombosis
6) Hypervolemia |
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Definition
4.
PV is associated with thrombosis, erythromelagia, aquagenic pruritis and splenomegaly due to mutation in JAK2 cytoplasmic kinase.
Fever has not been linked |
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Term
| Describe the process of working with a differential diagnosis of Polycythemia vera in a patient with elevated Hb and HCT. |
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Definition
P. vera is an absolute erythrocythemia that is EPO-insensitive
1) Relative (decreased plasma volume in dehydration or burn) vs. Absolute (Epo-sensitive vs. Epo-insensitive)
2) Absolute erythrocytosis
- Epo-sensitive (appropriate or inappropriate with renal/endocrine lesions)
- Epo-insensitive (P. vera) |
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Term
| Describe how you can distinguish Polycythemia vera from secondary erythrocythemia. |
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Definition
RCV will be increased in both
SHORT: P vera= splenomegaly, normal O2 saturation and decreased EPO.
1) Splenomegaly only found in P. vera
2) Normal O2 sat in P. vera
3) Leukocytosis and thrombocytosis only in P. vera
4) Pan-hyperplasia in marrow of P. vera (only erythro otherwise)
5) Decreased EPO levels in P. vera |
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Term
| How can you make a definitive diagnosis of Polycythemia vera? |
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Definition
Need either both major and a minor OR 1st major and 2 minor
Major criteria
1) Hgb > 18.5 in men, or 16.5 in women
or
- Hgb or Hct >99th percentile of reference
or
- Hgb >17 in men or 15 in women if associated with 2g increase cannot be attributed to correction with iron
or
- RCM >25% above mean predicted
2) JAK2V617F mutation (also can be found in Essential thrombocythemia)
Minor
1) BM trilineage myeloproliferation
2) Subnormal serum Epo level
3) EEC growth |
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Term
| What is the major treatment option for Polycythemia vera? |
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Definition
Get that hematocrit < 0.45 with Phlebotomy
1) Cytoreductive therapy with Hydroxyurea or IFN (younger or pregnant)
2) Antithrombotic with Aspirin
**Chlorambucil has acute leukemia risk** |
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Term
Patient presents complaining of headaches and visual disturbances.
On PE, you notice a little splenomegaly and order some blood work, with is negative for anemia, but there is mild leukocytosis and platelet count is 500 X 10^9/L
What is on your differential and how do you proceed? |
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Definition
Vascular headaches fit Essential thrombocythemia (ET), but it is unclear and PE findings are non-specific.
- Reactive thrombocythemia can be seen in 1) post-splenectomy or 2) hyposplenism (amyloidosis) and must be ruled out
- Rebound thrombocytosis is also seen with folate/B12 repletion, and this may also occur with chronic inflammation or iron deficiency.
ET differs from reactive T is a few ways
1) chronic thrombocytosis
2) thrombosis
3) splenomegaly
4) marrow fibrosis
5) abnormal cytogenetics |
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Term
Which of the following is not associated withs secondary thrombocytosis
1) Splenectomy/hypospenism
2) Chronic inflammation
3) Iron deficiency
4) Folate/B12 repletion
5) Splenomegaly |
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Definition
5
Splenomegaly is characteristic of essential thrombocythemia, while the others are found in secondary, reactive causes. |
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Term
| What diagnostic criteria are required to make a diagnosis of Essential Thrombocythemia (ET)? |
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Definition
NEED ALL 4 and treat high-risk patients (>60 with thrombosis h/x) with platelet-lowering agent (hyroxyurea),
1) Platelets > 450 X 10^9
2) Megakaryocyte proliferation with large/mature morphology (no erythrocyte or granulocyte)
3) JAK2V617F or other clonal marker with no evidence of RT
4) Not CML, PV, PMF, MDS or other myeloid neoplasm |
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Term
| How can essential thrombocythemia be treated? |
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Definition
1) First line is platelet-lowering agent like HYDROXYUREA
2) Anagrelide
- block megakaryocyte differentiation but cause headache, palpitation, fluid retention or diarrhea
3) IFN-a reduces platelet count but has side effects |
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Term
| How can you most effectively distinguish Reactive thrombocythemia from ET? |
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Definition
ET will have
1) chronic thrombocytosis
2) splenomegaly
3) thrombosis/hemorrhage
4) marrow fiboris
5) abnormal cytogenetics |
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Term
| What are the major clinical characteristics of Primary Myelofibrosis? |
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Definition
1) Older patient (600 presents with symptoms related to pancytopenia and splenomegaly (more pronounced that ET or P. vera, usually)
2) Labs show Extra-medullary hematopoiesis
- tear-drop red cels
- nucleated red cells
- left shift
- attempt to tap marrow is "dry" |
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Term
Which of the following is not a characteristic feature of the peripheral blood in a patient with primary myelofibrosis (Agnogenic myeloid metaplasma)?
1) Tear drop red cells
2) Nucleated red cells
3) Promyelocytes
4) Polychromasia
5) Pancytopenia |
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Definition
4- Polychromasia would indicate a bone marrow response, which is not seen with PMF. More likely seen in MDS
PMF occurs when bone marrow is replaced by collagen fibrosis, impairing the patient's ability to generate new blood cells resulting in a progressive pancytopenia. |
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Term
| What conditions can cause secondary myelofibrosis? |
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Definition
Many MPS (CML or PV)- must be ruled out to prove primary disorder.
1) Hematological diseases
2) Metastatic cancer
3) Infections (TB, Histo, HIV)
4) Autoimmune disease
5) Vitamin deficiency
MANY more |
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Term
| How is Primary Myelofibrosis treated? |
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Definition
1) In kids, Allogeneic SCT is curative
2) In adults and kids who are not candidates, Symptomatic treatments includes JAK inhibitor |
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Term
| How do Myelodysplastic syndromes differ from Myeloproliferative disorders? |
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Definition
1) MDS are characterized by dysplastic and ineffective blood cell production and risk of transformation to acute leukemia
2) MPD (P. vera, ET, PMF) involve clonal expansions of multi-potential hematopoietic progenitor cells where one cell type dominates |
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Term
| How can Myelodysplastic syndromes be diagnosed/worked up? |
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Definition
Symptoms are non-specific and need labs
1) CBC
- Leucocytes, Erythrocytes and Platelets may all be low
2) Peripheral blood smear (HALLMARK)
- Hypo-granulated neutrophils with abnormal nuclei
- Giant platelets
- Polychromasia
- Macrocytosis and anisopoikilocytosis
3) Bone marrow aspiration with prussian blue
- Normal/increased cellularity
- Megaloblastic changes
- Ringed sideroblasts, micro-megakaryocytes, increased myeloblasts, hypo-granular promyelocytes.
4) Cytogenetic analysis of marrow cells
- Clonal abnormalities 30-79%
5) HLA typing for young patient or older patients with good performance
6) Chemistry- RBC folate, B12, iron studies, EPO |
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Term
| What major factors determine the prognosis of a patient with MDS? |
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Definition
International Prognostic SS uses BM blasts (%), Karyotype and Cytopenias to score 0-2
The higher the score, the greater chance of transforming to AML. |
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Term
| What are the treatment recommendations for patients with MDS? |
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Definition
Depends on patient's IPSS risk group (BM blasts, karyotypes, cytopenia), age and performance status).
1) Supportive care- transfusion and cytokine support
- For IPSS low/intermediate-1
2) Low intensity therapy- Azacitidine and Decitabine (cytosine nucleoside analogs)
- For high-risk that is not candidate for HSCT
- Lenalidomide for MDs with deletion of 5q
3) High intesnsity
- HSCT for high-risk IPSS |
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