6. Polycythemia vera – clinical features
• May be incidental finding of high Hgb/HCT
• Non-specific complaints: HA, weakness, dizziness, excessive sweating
• Pruritus
– Typically after hot bath/shower or rubbing of skin
– Presumed 2/2 mast cell degranulation –
histamine, prostaglandins, etc...(unproven)
– Consistent with finding that ASA can relieve pruritus in some patients
• Erythromelalgia/acral paresthesias
– Burning pain/parasthesias in hands/feet accompanied by erythema, pallor, or
cyanosis
– Thought to be 2/2 microthrombi; associated with thrombocytosis
– Responds dramatically to ASA or reduction of plt count to normal
7. Polycythemia vera – clinical features
• Thrombosis (venous or arterial)
– Risk factors include age, h/o prior thrombosis, leukocytosis
• Extreme thrombocytosis and CV risk factors may also be risk factors
(controversial)
– Suspect PV in patients with unusual sites of thrombosis, e.g. Budd-Chiari, portal,
splenic, or mesenteric vein thrombosis, particularly in women < 45
– Transient visual disturbances (e.g. amaurosis fugax, migraine)
• Splenomegaly +/- hepatomegaly
10. Polycythemia Vera
Course and Prognosis
• Median survival is ~ 14 years
• Chronic phase may last for years
• Progression to:
– Myelofibrosis (~10% at 10 years)
– AML (1-5% at 10 years)
• Thrombosis major source of morbidity and mortality
11. Polycythemia Vera
Treatment
• Low dose aspirin indicated for all patients
• Phlebotomy: Goal to Hct < 45 (< 42 in females)
• Myelosuppression (usually hydroxyurea)
– Typically used in patients at high risk for thrombosis (age > 60 or
prior h/o thrombosis)
• Alpha-interferon (younger high-risk patients)
12. • A 66 year-old woman presents with
headaches and recurrent TIA symptoms
• CBC reveals thrombocytosis:
13. Differential Diagnosis of Thrombocytosis
• Reactive (secondary) thrombocytosis
– Infection/inflammation
– Iron deficiency
– Chronicity of thrombocytosis helpful
• Primary thrombocytosis
– Essential thrombocythemia
– (masked) polycythemia vera
– Need to exclude CML (BCR-ABL)
14. Essential Thrombocythemia
Clinical Features
• Chronic thrombocytosis (often extreme, > 1 x 106/µL)
• Many patients are asymptomatic
• Vasomotor symptoms: headaches, syncope, visual disturbances, atypical
chest pain, erythromelalgia (typically ASA-responsive)
• Thrombosis major cause of morbidity and mortality
– Both arterial and venous; unusual sites
– No clear association with platelet count
• Paradoxical increase in bleeding complications
– Risk factors/associations:
• Extreme thrombocytosis > 1 million (controversial)
• Use of ASA > 325 mg/day or other NSAIDs
• Acquired VWD
• Splenomegaly
15. Essential Thrombocythemia
Diagnostic Criteria
• Platelet count ≥ 450,000
• JAK2 V617F+ OR no evidence of reactive thrombocytosis
• Not meeting WHO criteria for other MPNs (e.g PV, CML)
• Megakaryocyte proliferation with large and mature morphology;
no or little granulocyte or erythroid proliferation
- ALL FOUR CRITERIA ARE “REQUIRED”
17. Essential Thrombocythemia
Course and Treatment
• Survival curves near age-matched controls
– Thrombosis major cause of morbidity and mortality
– Progression to myelofibrosis in ~5% and AML in ~1-5%
• Low dose aspirin indicated for all patients without history of
bleeding
• Myelosuppresive therapy for high-risk patients (age > 60 OR
h/o thrombosis)
– Hydroxyurea, anagrelide
• Treatment based on platelet count alone is controversial
18.
19.
20.
21. • A 57 year-old man presents with
fatigue, anorexia, and night sweats
• He also complains of abdominal discomfort
and early satiety
• CBC reveals pancytopenia with an abnormal
peripheral smear
Seg 35, bands 20, metamyelocytes 10, myelocytes 8, promyelocytes 4, blasts 3, teardrop
RBCs, nRBCs
22. Primary Myelofibrosis
Differential Diagnosis
• Reactive myelofibrosis
– Marrow infiltration with cancer
– Infections (mycobacterial or fungus)
– Myelodysplasia
• Other MPNs
• Work-up
– Bone marrow biopsy
– Genetic testing for JAK2 V617F and BCR-ABL
23. Primary myelofibrosis – clinical features
• Severe fatigue, weight loss, fevers, night sweats
• Splenomegaly, often massive
– LUQ discomfort/pain, early satiety
• Hepatomegaly
– Portal HTN related to HSMG – ascites, varices, UGIB
– Portal vein thrombosis
• Extramedullary hematopoiesis
– Foci can occur in almost any organ
• Cytopenias (but can also have leukocytosis, thrombocytosis)
• Leukoerythroblastic reaction
24. Leukoerythroblastic Reaction
Triad:
• Tear drop RBC
• Nucleated RBC
• Immature myeloid cells
Associated with marrow
infiltration
• Myelofibrosis
• Cancer
• Certain infections
27. Primary Myelofibrosis
Course and Prognosis
• Median survival of only 3 years
• Bone marrow failure
– Progressive cytopenias
– RBC transfusion dependence
– Susceptibility to infections
– Hemorrhage
• Evolution to AML
30. Primary myelofibrosis – treatment
• Supportive care
– Transfusions
– ESAs – not generally effective in PMF
• Hydroxyurea
– Can be effective in controlling leukocytosis and/or thrombocytosis
– Can ameliorate splenomegaly
– Myelosuppression Is limiting factor
• Splenectomy
– Indicated for severe symptoms related to SMG
– May be helpful for improving anemia and/or thrombocytopenia
• Splenic irradiation
– Considered for poor surgical candidates
– Benefits are transient (3-6 months)
• BMT
– Not an option for many patients
31. Primary myelofibrosis – treatment
• Well tolerated – initial study with higher doses of thalidomide poorly tolerated
• 28% with ongoing response
– Durable treatment response for anemia and thrombocytopenia, not SMG