CH6 - 4) Myeloproliferative Disorders Flashcards
What are myeloproliferative disorders?
Neoplastic proliferation of mature cells of myeloid lineage; disease of late adulthood (average age is 50-60 years)
What does myeloproliferative disorders result in?
high WBC count with hypercellular bone marrow
How are myeloproliferative disorders characterized?
Cells of all myeloid lineages are increased; classified based on the dominant myeloid cell produced
What are the complications for myeloproliferative disorders?
1) Increased risk for hyperuricemia and gout due to high turnover of cells 2) Progression to marrow fibrosis or transformation to acute leukemia
What is chronic myeloid leukemia?
Neoplastic proliferation of mature myeloid cells, especially granulocytes and their precursors;
In chronic myeloid leukemia what are characteristically increased?
basophils
What is chronic myeloid leukemia driven by?
driven by t(9:22) - Philadelphia chromosome - which generates a BCR-ABL fusion protein with increased tyrosine kinase activity
What is the first line treatment for chronic myeloid leukemia?
imatinib,
What does imatinib do?
It blocks tyrosine kinase activity
How is splenomegaly related to chronic myeloid leukemia?
Splenomegaly is common, enlarging spleen suggests accelerated phase of disease;
In chronic myeloid leukemia what usually follows after splenomegaly?
transformation to acute leukemia
What can chronic myeloid leukemia transform to?
AML in 2/3 of cases or ALL in 1/3 of cases since mutation is in a pluripotent stem cell,
What is a leukemoid reaction?
Reactive neutrophilic leukocytosis
How is CML distinguished from a leukemoid reaction (reactive neutrophilic leukocytosis)?
Negative LAP stain, inc basophils, t(9;22)
What is a LAP stain?
leukocyte alkaline phosphatase (LAP) stain
How is a LAP stain related to a leukemoid reaction?
granulocytes in a leukemoid reaction are LAP positive
Why are basophils useful in determining the difference between a leukemoid reaction and CML?
Basophils are increased in CML and are absent with a leukemoid reaction
How is t(9;22) useful in determining the difference between a leukemoid reaction and CML?
It is present in CML and absent in leukemoid reaction
What is polycythemia vera?
Neoplastic proliferation of mature myeloid cells, especially RBCs
In polycythemia vera, in addition to the RBC increase what are also increased?
Granulocytes and platelets are also increased
What mutation is associated with polycythemia vera?
JAK2 kinase mutation
What are the clinical symptoms for polycythemia vera due to?
they are mostly due to hyperviscosity of blood
What are the clinical symptoms for polycythemia vera?
- Blurry vision and headache 2. Increased risk of venous thrombosis (e.g., hepatic vein, portal vein, and dural sinus) 3. Flushed face due to congestion (plethora) 4. Itching, especially after bathing (due to histamine release from increased mast cells)
What is plethora in relation to PV?
One of the clinical symptoms; flushed face due to congestion
Why is there itching in PV?
Itching, especially after bathing due to histamine release from increased mast cells
What is the treatment for PV?
phlebotomy;
What is the second-line therapy for PV?
hydroxyurea.
What happens to a patient with PV who goes intreated?
Without treatment, death usually occurs within one year.
How can PV be distinguished from reactive polycythemia?
- In PV, erythropoietin (EPO) levels are decreased, and Sao, is normal. 2. In reactive polycythemia due to high altitude or lung disease, SaO2 is low, and EPO is increased. 3. In reactive polycythemia due to ectopic EPO production from renal cell carcinoma, EPO is high, and Sao2 is normal.
What are the EPO and SaO2 levels in PV?
EPO is decreased and SaO2 is normal
What are the EPO and SaO2 levels in reactive polycythemia due to high altitude or lung disease?
EPO is increased and SaO2 is low
What are the EPO and SaO2 levels in reactive polycythemia due to renal cell carcinoma?
EPO is high, SaO2 is normal
What is essential thrombocythemia?
Neoplastic proliferation of mature myeloid cells, especially platelets
In ET, in addition to the platelets what else is increased?
RBCs and granulocytes are also increased.
What is mutation is ET associated with?
JAK2 kinase mutation
What do the symptoms of ET result from?
they are related to an increased risk of bleeding and/or thrombosis.
What do the symptoms of ET rarely progresses to?
marrow fibrosis or acute leukemia
In ET what is there no significant risk for?
hyperuricemia or gout
What is myelofibrosis?
It is neoplastic proliferation of mature myeloid cells, especially megakaryocytes
What mutation is associated with myelofibrosis?
JAK2 kinase mutation in 50% of cases
In myelofibrosis, what causes marrow fibrosis?
Megakaryocytes produce excess platelet-derived growth factor (PDGF) causing marrow fibrosis
What are the clinical features for myelofibrosis?
1) splenomegaly 2) leukoerythroblastic smear 3) Increased risk of infection, thrombosis, and bleeding
In myelofibrosis what is splenomegaly due to?
extramedullary hematopoiesis
In myelofibrosis what is the leukoerythroblastic smear?
It’s tear-drop RBCs, nucleated RBCs, and immature granulocytes
In myelofibrosis what is their an increased risk for?
increased risk for infection, thrombosis, and bleeding
