Myeloproliferative Disorders (MPD) Flashcards
What are the four types of myelproliferative disorders?
Chronic Myeloid Leukemia
Polycythemia vera
Essential thrombocythemia
Myelofibrosis
What are myelproliferative disorders? What do you see on blood work? What kind of complications do they cause?
Neoplastic proliferation of myeloid cells of myeloid lineage,; disease of late adulthood (average age is 50-60 years). High WBC count with hypercellular bone marrow. Cells of ALL myeloid lineages are increased and classified based on dominant myeloid cell produced. Complications include 1. increased risk for hyperurecimia and gout due to high turnover of cells 2. Progression to marrow fibrosis or transformation to acute leukemia
What is Chronic myeloid leukemia? What cells are characteristically increased? What mutation drives it? How would you treat and how does the medication work?
Neoplastic proliferation of mature myeloid cells, especially granulocytic and their precursors; basophils characteristically increased. T(9;22) Philadelphia chromosome generates BCR-ABL fusion protein with increased tyrosine kinase activity. Tx is imatinib which blocks this activity.
What physical finding is common in CML? What does it suggest? What can it transform into? Why?
Splenomegaly suggests progression to accelerated phase of disease. Can transform to AML (2/3 of cases) or ALL (1/3 of cases) since mutation is of pluripotent stem cell
Does CML or reactive neutrophilic leukocytosis (from a leukemic reaction) stain positive for leukocyte alkaline phosphotase (LAP)?
Leukemoid reaction. Also no increase in basophils and no t(9;22)
What is polycythemia vera? Which mutation is it associated with?
Neoplastic proliferation of mature myeloid cells, especially RBCs. Granulocytes and platelets are also increased. Associated with JAK2 mutation.
A 32 year old woman comes to you with complaints of blurry vision and a headache that started two weeks ago. Her face looks flushed. She mentioned that she itches constantly after taking a hot shower. What does she have? Explain what is causing her symptoms. Tx?
She has polycythemia vera. Clinical symptoms are due to hyperviscosity of the blood. She has increased risk of venous thrombosis e.g. Hepatic, portal veins and dural sinuses. Flushed face is due to congestion. Itching is due to histamine release from increased mast cells. Tx is phlebotomy, 2nd line tx is hydroxy urea which prevents DNA s phase synthesis by blocking ribonucleotide reductase.
Which disease has low EPO, normal SaO2?
Polycythemia vera
Which disease has increased EPO, low SaO2?
Reactive polycythemia due to high altitude or lung disease.
Which disease has increased EPO, and normal SaO2?
Reactive polycythemia due to ectopic EPO production from renal cell carcinoma
What is essential thrombocythemia? What mutation is it associated with? What are symptoms related to? Can it progress to acute leukemia? Risk for hyperuricemia or gout?
Neoplastic proliferation of mature myeloid cells, especially platelets. RBCs and Granulocytes are also increased. Associated with JAK 2 kinase mutation. Symptoms related to increased risk of bleeding and/or thrombosis. Rarely progresses to marrow fibrosis or acute leukemia. No significant risk for hyperuricemia or gout.
What is myelofibrosis? What mutation is it associated with? What produce is produced in excess and what does it cause?
Neoplastic proliferation of mature myeloid cells, especially megakaryoctytes. Associated with JAK2 kinase mutation in 50% of cases. Megakaryocytes produce excess PDGF causing marrow fibrosis.
What are the clinical features of myelofibrosis?
- Splenomegaly due to extramedullary hematopoiesis
- Leukoerythroblastic smear (tear drop RBCs, nucleated RBCs and immature Granulocytes)
- Increased risk of infection, thrombosis and bleeding
