Hyperproliferative Disorders Flashcards
What is polycythemia Vera
Myeloproliferative neoplasm (MPN)
• Polycythemia Vera (PV)
• Clonal hematopoetic stem cell disorder
• Accumulation of RBCs, granulocytes & platelets
• Occurs due to JAK2 mutation
• Excess blood cell production
S/s of polycythemia Vera
Thrombocytosis, leukocytosis or splenomegaly
• Initial presenting manifestation of PV
• Incidental discovery of elevated H&H or RBC
• Erythrocytosis
• Vertigo, tinnitus, headache, visual
disturbances or TIAs
• Systolic hypertension
• Arterial/Venous thrombosis
• Hepatic venous thrombosis
• Digital ischemia, bruising, epistaxis, GI
hemorrhage
• Vascular stasis or thrombocytosis
• von Willebrand disease
• Erythromelalgia
• Hyperuricemia
Diagnostics of polycythemia Vera
Erythrocytosis, leukocytosis, thrombocytosis and/or splenomegaly
• Suspect PV
• Hepatic vein thrombosis,
• Suspect PV
• Elevated H&H or RBC
• Consider other etiology before PV
• DDx high altitude, pulmonary disease , sleep apnea.
• Laboratory Studies
• Serum erythropoietin (EPO) level
• Peripheral blood mutation screening for JAK2 V617F
• Normal or elevated EPO level and no JAK2 V617F mutation
• Rules out PV
• Sustained H&H elevation, subnormal serum EPO level & JAK2
V617F mutation
• Meets diagnostic criteria
• BM Bx not required
• Unless suspect disease evolution
• WHO Major Criteria using WHO criteria
• HgB >16.5 g/dL in men or >16.0 g/dL in women
• Hct >49% in men or >48% in women
• Bone marrow biopsy
• Hypercellularity
• JAK2 V617F mutation
• Minor criterion
• Serum erythropoietin level below reference range for normal
Polycythemia Vera treatment
Induce Fe+ deficiency
Phlebotomy
• HgB <14 g/dL & Hct <45% (male)
• HgB <12 g/dL & Hct <42% (female)
Maintenance of H&H
• Indicated for thrombosis
Anticoagulant
• Requires no therapy
• Add allopurinol if chemotherapy utilized
Asymptomatic hyperuricemia
• ruxolitinib (Jakafi)
• JAK inhibitor
Symptomatic splenomegaly
What is essential thrombocytosis
Other designations
• Essential thrombocythemia
• Idiopathic thrombocytosis
• Primary thrombocytosis
Epidemiology
• 1-2/100,000
• Female predominance
Clonal hematopoietic stem cell disorder
• Mutations in JAK2, MPL, & CALR
• Overproduction of platelets
Other causes
• Ex. Hemorrhage, malignancy, surgery, infections (not all
inclusive)
S/s of essential thrombocytosis
• Thrombosis, bleeding, 1st trimester fetal loss
• Bleeding
• Acquired von Willebrand disease
Complications of essential thrombocytosis
Complications
• Mild neutrophilic leukocytosis
• Blood smear
• Remarkable for number of platelets & size
Lab findings in essential thrombocytosis
• Mild neutrophilic leukocytosis
• Blood smear
• Remarkable for number of platelets & siz
Diagnostics of essential thrombocytosis
• Disease tempo, vasomotor symptoms,
thrombotic/hemorrhagic events, CV risk factors
• Associated conditions with thrombosis
• Family Hx
• Assess spleen size
• Laboratory Studies
• CBC, peripheral smear, CMP, LDH, uric acid, Fe+ studies
• Peripheral blood fluorescence in situ hybridization (FISH) or
RT-PCR
• BCR-ABL1
• Looking to exclude CML
• Evaluate for von Willebrand disease
• Bone Marrow Biopsy
• Pathology review
• Trichrome and reticulin stains, cytogenetics, &
JAK2 mutations
• JAK2 negative
• Check CALR & MPL mutations
• Negative mutation
• Check other gene mutations
(ASXL1, EZH2, TET2, IDH1/IDH2,
SRSF2, or SR3B1 mutation
Essential thrombocytosis major and minor criteria
World Health Organization (WHO) 2016 Criteria
• Requires all four (4) major criteria or first three (3) major criteria + minor
criterion
• Major Criteria
• Platelet count ≥450 x 109/L (≥450,000/microL)
• Bone marrow biopsy
• Proliferation of megakaryocyte lineage
• Increased numbers of enlarged, mature megakaryocytes with
hyperlobulated nuclei
• No significant increase or left shift in neutrophil granulopoiesis or
erythropoiesis
• Very rarely minor (grade 1) increase in reticulin fibers
• WHO criteria for BCR-ABL1-positive CML, PV, MDS, primary myelofibrosis
not met
• Demonstration of JAK2, CALR, or MPL mutation.
• Minor Criteria
• Demonstration another clonal marker (ASXL1, EZH2, TET2, IDH1/IDH2,
SRSF2, or SR3B1 mutation)
• No identifiable cause of thrombocytos
Treatment for essential thrombocytosis
Not curative
• Not shown to prevent disease transformation
• Does not prolong survival
Available treatment options
• Migraine
• Lowering platelet count
• Erythromelalgia
• Aspirin or ibuprofen
• Reduce thrombotic events
• Low-dose aspirin
• Avoid aspirin w/ acquired von Willebrand syndrome
• Cytoreductive therapy + systemic anticoagulation +/- aspirin
• High-risk patients.
• Hydroxyurea
• First-line drug cytoreductive therapy
Symptoms control and minimizing complications
