Myeloproliferative Diseases Flashcards by Barrett Thompson

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

***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

How well did you know this?

Not at all

Perfectly

***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

How well did you know this?

Not at all

Perfectly

***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.

How well did you know this?

Not at all

Perfectly

***Diagnostic Criteria/Process of Primary Myelofibrosis

Hepatosplenomegaly, Constitutional Symptoms
Bone Marrow Biopsy
JAK2V617F check, Calrectin, and MLP check

How well did you know this?

Not at all

Perfectly

***Diagnostic Criteria/Process of Chronic Myeloid Leukemia

BCR-ABL fusion protein with t(9,22) detected using FISH or PCR

How well did you know this?

Not at all

Perfectly

***Complications of Polycythemia Vera

COMPLICATIONS:

THROMBOSIS
Acute Myeloid Leukemia

How well did you know this?

Not at all

Perfectly

***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

How well did you know this?

Not at all

Perfectly

***Causes of Increased Neutrophils

Neoplastic Causes:
• MF, PV, CML, ET

Drugs:
• CORTICOSTERIODS, LITHIUM
• Infection

Others: 
• Smoking Cigarettes 
• Obesity
• Inflammation
• Malignancy

How well did you know this?

Not at all

Perfectly

***Causes of Increased Eosinophils

Idiopathic Eosinophilia
Reactive Eosinophilia
Hypereosinophilia Sydrome - Idopathic, Chronic Eosinophilic Leukemia, Hematopoietic Neoplasma accompanied by eosinophilia

How well did you know this?

Not at all

Perfectly

***Mutation and MOA of Philadelphia Chromosome

t(9,22) BCR-ABL mutation

How well did you know this?

Not at all

Perfectly

***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

How well did you know this?

Not at all

Perfectly

***What does the Peripheral Blood Smear Look like in CML?

Agranular, Early Neutrophils

* Lots of Myelocytes (very early neurophil precursor)

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What are some potential causes of Increased Platelets?

*Other than neoplasms

Study These Flashcards

Splenectomy
Trauma
Malignancy
Iron Deficiency

What is the major difference between a myelodysplastic syndrome and a myeloproliferative neoplasm?

Study These Flashcards

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?

Study These Flashcards

Jak2-V617F (90%)

* Jak2 Exon12

What are the driver mutations that can lead to Essential Thrombocytosis or Myelofibrosis?

Study These Flashcards

Jak2-V617F
Calreticulin
MPL (TPO receptor)

Most common physical findings and symptoms of Polycythemia Vera.

Study These Flashcards

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?

Study These Flashcards

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?

Study These Flashcards

Lots of Platelets
Hypochromic RBCs
Increased Platelets

What are 5 predictors of thrombosis in a patient with Polycythemia vera?

Study These Flashcards

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?

Study These Flashcards

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 1. Correct Thrombocytosis 2. Withdraw ASPRIN and anti-thrombotics 3. 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?

1. Teardrop RBCs are KEY 2. Nucleated RBCs 3. Giant Platelets

What should you look for in the blood smear of a patient with Chronic Myelogenous Leukemia?

1. Agranular Neutrophils 2. 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

1. Chronic Myelocytic Leukemia (CML) • BCR-ABL mutation 2. Chronic Eosinophilic Leukemia (CEL) • FIP1L1-PDGFRA mutation

Myeloproliferative Diseases Flashcards

(36 cards)