Myeloproliferative Diseases Flashcards
What defines a myeloproliferative Disease?
Myeloproliferative Neoplasms
• hematopoietic neoplasms
• Single clone of cells is mutated early in the differentiation of blood cells
• cells can differentiate fully into red cells, platelets and neutrophils,
• longer are well controlled in number, but still function normally
What reason might cause Hemoglobin and Hematocrit to be artificially increased?
• what specific conditions would do this OTHER than Polycythemia Vera?
Decrease in Plasma Volume
Other Conditions:
Acute
• HUGE fluid loss from the body via vomiting, diarrhea, severe burns, diabetic ketoacidosis
Chronic
• Long and inappropriate use of diuretics
***What is the mechanism of action of the JAK-2 V617F mutation?
*This is the EPO receptor that is constantly stimulated no matter if EPO is there or not
***Diagnostic Criteria/Process of Polycythemia Vera.
- High RBC >18.5 (male) or >16.5 (female)
- Check JAK2V617F and EPO (MUST BE LOW)
- If EPO is low and not JAC2V617F, then check JAK2 Exon12
- Do bone marrow biopsy
***Diagnostic Criteria/Process of Essential Thrombocythemia.
- Sustained Platelet Count ≥ 450,000
- NO ELEVATED RED COUNT
- Look for 2˚ causes like iron deficiency, inflammation, or malignancies
- JAK2V617F check, then Calrectin and MLP if JAK is (-)
- BONE Marrow Biopsy to Confirm Dx. showing lots of Megs.
***Diagnostic Criteria/Process of Primary Myelofibrosis
- Hepatosplenomegaly, Constitutional Symptoms
- Bone Marrow Biopsy
- JAK2V617F check, Calrectin, and MLP check
***Diagnostic Criteria/Process of Chronic Myeloid Leukemia
BCR-ABL fusion protein with t(9,22) detected using FISH or PCR
***Complications of Polycythemia Vera
COMPLICATIONS:
- THROMBOSIS
- Acute Myeloid Leukemia
***Treatment of Polycythemia Vera
Treatment:
• Phlebotomy - target hct 45%
• Asprin - 100mg/day
Second Line Treatment:
• Hydroxyurea - bone marrow suppressant
3rd Line Treatment (if hydroxyurea fails)
• Interferon - good for pregnant women
• JAK2 inhibitors
***Causes of Increased Neutrophils
Neoplastic Causes:
• MF, PV, CML, ET
Drugs:
• CORTICOSTERIODS, LITHIUM
• Infection
Others: • Smoking Cigarettes • Obesity • Inflammation • Malignancy
***Causes of Increased Eosinophils
- Idiopathic Eosinophilia
- Reactive Eosinophilia
- Hypereosinophilia Sydrome - Idopathic, Chronic Eosinophilic Leukemia, Hematopoietic Neoplasma accompanied by eosinophilia
***Mutation and MOA of Philadelphia Chromosome
t(9,22) BCR-ABL mutation
***MOA of present best therapy for CML
Imatinib is the main drug used to bind in the ATP binding site of the mutant BCR-ABL Tyrosine Kinase
***What does the Peripheral Blood Smear Look like in CML?
- Agranular, Early Neutrophils
* Lots of Myelocytes (very early neurophil precursor)
What will your EPO levels look like in PV?
They should be low because the JAK2 V617F mutation activates the EPO receptor in the absence of EPO
What are some potential causes of Increased Platelets?
*Other than neoplasms
- Splenectomy
- Trauma
- Malignancy
- Iron Deficiency
What is the major difference between a myelodysplastic syndrome and a myeloproliferative neoplasm?
In a myelodysplastic syndrome most cells die in the bone marrow so you actually gets cytopenias rather than cyotosis
What are the possible driver mutations causing polycythemia vera?
- Jak2-V617F (90%)
* Jak2 Exon12
What are the driver mutations that can lead to Essential Thrombocytosis or Myelofibrosis?
- Jak2-V617F
- Calreticulin
- MPL (TPO receptor)
Most common physical findings and symptoms of Polycythemia Vera.
Physical Findings:
• Splenomegaly (MOST COMMON SYMPTOM)
• Skin/conjunctival Plethora (2nd Most common)
• Hepatomegaly
Symptoms:
• Headache
• Weakness
• Pruritus
What is the principle cause of death in polycythemia vera?
• 2nd most common?
• Median survival from initiation of Phlebotomy?
- THROMBOSIS
- Acute Myeloid Leukemia (2nd most common)
*14 year survival from intitiation of phlebotomy
What is often seen in the peripheral smear of a person with Polycythemia Vera?
- Lots of Platelets
- Hypochromic RBCs
- Increased Platelets
What are 5 predictors of thrombosis in a patient with Polycythemia vera?
Age > 65 Previous thrombosis Elevated Leukocyte Count (15,000) Cardio vascular risk factors Elevated Hematocrit
What conditions should be on your differential diagnosis for a high platelet count?
- Inflammation
- Trauma
- Malignancy
- Iron Deficiency
- Splenectomy
- Myeloproliferative Neoplasm
What liver problems might result from having a JAK2 V617F mutation?
Budd-Chiari Symdrome (40-58% have JAK2 V617F)
Portal Vein Thrombosis (33% have JAK2 V617F)
**Pts. with JAK2 V617F may also be susceptible to SVT
What secondary complication may result when a patient has a platelet count over 1.5 million?
• What neoplasm is most likely the cause?
Von Willebrand’s Disease
**Loss of vWF multimers causing issues with bleeding
*Essential Thrombocythaemia is often the cause
What can you do for a patient with major bleeding problems due to Essential Thrombocythaemia?
• What is likely the root cause of this major bleeding problem?
Von Willibrand’s disease can cause excessive bleeding in ET patients with platelets above 1.5 million
- Correct Thrombocytosis
- Withdraw ASPRIN and anti-thrombotics
- Plasma Products that contain vWF, antifibrinolytics, DDVAP (diargininedivasopressin, but not with platelets above 1.5 million)
What therapies can you give to someone with Essential Thrombocytopenia?
- HIGH RISK patients need platelet Reduction
1st line
• Hydroxyurea (like in PV)
2nd line
• Anagrelide
• Inferferon for Pregnant Women
**What make a patient with ET “high risk and thus in need of platelet reduction”?
- Over 60 years old
- Previous Thrombosis
- Platelet count above 1.5 million
- Previous Hemorrhage Related to ET
- Diabetes or Hypertension
What 2 myeloproliferative disorders historically causes Splenomegaly?
• What is the root cause of this?
Primary Myelofibrosis
Chronic Myelocytic Leukemia
**Hematopoeitic Cells are pushed out of the marrow and must try to make it up in the spleen
What are some clinical findings you might expect with Primary Myelofibrosis?
- hepatoSPLENOMEGALY
- Fatigue
- Anemia
- Weight Loss
- Night Sweats
- Portal Hypertension
What are you looking for in the peripheral smear of a person with myelofibrosis?
- Teardrop RBCs are KEY
- Nucleated RBCs
- Giant Platelets
What should you look for in the blood smear of a patient with Chronic Myelogenous Leukemia?
- Agranular Neutrophils
- Promyelocytes
**Overall, lots of early white cells in the periphery
How do patients often present with CML?
- Not current illness, but have ELEVATED neutrophils
- Palpable Spleen
- Smear showing early neutrophils, mainly MYELOCYTES
What do myelocytes and promyelocytes look like?
Blasts with Granular Cytoplasm
What 2 myeloproliferative conditions can imatinib be used to treat?
• Associated Mutation
- Chronic Myelocytic Leukemia (CML)
• BCR-ABL mutation - Chronic Eosinophilic Leukemia (CEL)
• FIP1L1-PDGFRA mutation
