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52 Cards in this Set
- Front
- Back
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What is the definition of a myeloproliferative neoplasm?
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Group of clonal myeloid neoplasms in which a genetic alteration occursin a hematopoietic progenitor cell leading to its proliferation resulting in an increase in the number of peripheral WBCs, RBCs, platelets, or a combination thereof
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What cells come from the myeloid cells?
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RBCs
Platelets WBCs (not lymphocytes, though) |
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What are the feature of chronic myeloid leukemia?
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Leukocytosis with a left shift
Other findings: Mild anemia Normal-elevated platelet count Peripheral blood basophilia |
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What are the features of polycythemia vera?
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Elevated RBC indices (RBC count, Hgb, Hct)
Also: Mild leukocytosis Thrombocytosis |
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What are the features of essential thrombocytosis?
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Elevated platelet count
Also: Mild leukocytosis Polycythemia |
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What are the findings in primary myelofibrosis?
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Leukoerythroblastic blood smear:
-Tear drops -Nucleated RBCs -Early myeloid precursors Symptoms: -Hepatomegaly -Splenomgaly -Lymphadenopathy |
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What is the age of people who get CML?
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65
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What are risk factors for CML?
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Prior radiation
Exposure to organic solvents Age Gender: male > female However: 99% of people have no risk factors |
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What are the three phases of CML?
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Chronic phase
Accelerate phase Blast phase |
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How do you distinguish between the phases of CML?
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The number of blasts: increased number of blasts, you go to a different phase.
Based on the phase, you have different treatments and outcomes |
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What percentage of blasts is found in the accelerated phase of CML? Blast phase?
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Accelerated: 10-19%
Blast phase: >20% In the peripheral blood or in the bone marrow |
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What is the hallmark genetic finding of CML?
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The PHILLY CHROMOSOME!
A balanced chromosomal translocation: -Break near TRK on chromsome 9 (long arm) -Break near BCR on chromsome 22 You get chronic expression of Bcr-Abl |
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What gene product is sufficient and necessary for CML?
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Bcr-Abl
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What's the clinical presentationof CML?
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15% asymptomatic
Fatigue, weight loss, fever Abdominal fullness, pain, early satiety due to splenomegaly Easy bruising/purpura (dysfunctional platelets) Leukostasis (only when WBC>250K) (thick blood.) |
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In what abnormal location do RBCs develop in CML? Why?
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Speen (this is the cause of splenomegaly)
They develop there because the marrow gets too full and they return to the place where they developed in the embryo. |
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What does a blood smear of CML look like?
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1. Leukocytosis with a left shift
2. Normocytic anemia 3. Thrombocytopenia in 50% of pts 4. Absolute eosinophilia 5. Absolute increase in basophils |
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What is required for a diagnosis of CML?
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The philly chromosome: t(9,22)
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What are mechanisms of diagnosing the philly chromosome?
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Karyotyping
FISH RT-PCR for Bcr-Abl |
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When you do fish for the philly chromosome, what's a positive result?
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Yellow!
Shows overlapping of 9 and 22 which are tagged with either red or green; they shouldn't overlap normally |
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What's the best test for CML diagnosis?
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RT-PCR
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What were the early therapies for CML?
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Interferons: they're horrid for patients, though...lots of side effects.
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What is the mechanism of the drugs that best treat CML?
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Prevent ATP binding to the Acr TK. No activity FTW!
Slow dying off of the cells that produce the TK? |
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What is the most common mechanism of resistance to the tyrosine kinase inhibitors?
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Mutation of the site that the inhibitors bind to.
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What is the typical way that CML is treated?
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1st line:
1. Imatinib (gleevec) Second line: different TK inhibitors 1. Dasatinib 2. Nilotinib 3. Bone marrow transplant 4. Clinical trial |
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What is the enzyme that underlies the myeloproliferative disorders other than CML?
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JAK2
Janice associated kinase, a tyrosine related kinase |
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What protein is almost always mutated in polycythemia vera?
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JAK2
Lower rate in EMT,other disorders |
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What is the impact of a mutation in JAK2 in the myeloproliferative disorders?
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Constituitive activation
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What's the definition of a relative polycythemia?
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High concentration of red cells due to a non-proliferative cause
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What are common causes of relative polycythemia?
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Dehydration: depletes plasma volume-->relative polycythemia
Stress erythrocytosis: contraction in plasma volume in hypertensive obese men. |
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What are causes of absolute polycythmia?
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1, Intrinsic to the bone marrow, more red cells are made
2. Stimulus to the bone marrow from the body to make more red cells |
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What are common causes of absolute polycythemia?
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1. Primary polycythemia vera
2. Hypoxia (CO poisoning) 3. Carboxyhemoglobinemia 4. Cushing's/corticosteroids 5. Erythropoietin secreting tumors |
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What are symptoms of primary polycythemia vera?
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Nonspecific complaints: headache, weakness,dizziness, excessive sweating
Puritis FOLLOWING A SHOWER!!!! Erythromegalia (burning pain in feet/hands) Arterial/DVT |
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Why does someone itch after a shower if they have PCV?
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Mast cells are overproduced, and the heat stimulates the cells to release their contents, causing an itch.
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What are the diagnostic criteria for primary PV?
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1. High red count
2. JAK2 mutation |
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What labs should you do if you suspect someone has PV?
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Epo
JAK2 If Epo low and JAK2, then PV. If none of those, do a bone marrow biopsy |
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What is the primary risk to people with PCV?
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Blood clots
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What patients are at a particularly high risk for clots with PV?
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Any one of them can give you a risk for clots
>70 previous thrombosis platelets > 1,500,000/uL CV risk factors |
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What is the treatment for a high risk patient with PV? Low risk?
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Low risk: phlebotomy, low dose asprin
High risk: plebotomy + asprin + hydroxyurea |
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What is the definition of thrombocytosis?
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Platelets > 450,000/uL
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What are the two types of thrombocytosis?
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Primary
Secondary In order to diagnose it as a primary, you've got to rule out all of the possible secondary causes = big work up |
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What are the causes of secondary thrombocytosis?
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1. Malignancies
2. Infections, inflammatory disorders 3. Meds 4. Post surgery 5. Connective tissue disorders 6. Iron deficiency anemia 7. Splenectomy |
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What are the common symptoms of essential thrombocytopenia?
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30-50% asymptomatic
Headache, syncope, chest pain, etc. Some have thrombosis Early satiety and bloating due to splenomegaly JAK2 in 50% |
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What are the major risks for people with ET?
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Blood clots (main risk)
Evolution to myelofibrosis or AML |
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Who is at high risk for thrombosis with ET?
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Age > 60
Prior thrombosis Long-term exposure to a platelet count > 1,000,000 |
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What's the treatment of ET?
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Low risk: asprin
High risk: hydroxyurea + asprin |
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How can ET cause problems with vWF?
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There are so many platelets there that they soak up all of the vWF.
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What are they symptoms of primary myelofibrosis?
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Fatigue
Splenomegaly, hepatomegaly Fever and night sweats Anemic syndromes |
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What are findings in the peripheral smear of primary myelofibrosis?
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Schistocytes
Odd looking blood cells. |
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What do you have to find to diagnose primary myeloid fibrosis?
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Collagen scar/fibrosis in the bone
Don't have evidence of another cause (CML, PV, MDS,etc.) Jax2mutation |
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What are the risks for PMF?
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Transformation into AML
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What makes someone at a higher risk for transformation in PMF?
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Age
Anemia Blasts WBC count Symptoms |
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What's the treatment for PMF?
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Low risk with symptoms:
-hydroxyurea -androgens, corticosteroids -splenic ablation/removal High risk: (and under 55) Bone marrow transplant |
