Name: Rhys Coo Student ID: 1-241-02598

Date: October 12, 2024

Polycythemia
Introduction:
• Classically Define as increased hematocrit level above normal
• In clinical Setting:
o Polycythemia occurs when hemoglobin and RBC count are elevated
o Reflecting an elevation of the total erythrocyte volume
• Two General Kinds:
o Absolute Polycythemia
§ Elevated total red cell mass
o Relative Polycythemia
§ Normal total red cell mass
§ However, hematocrit is increased because plasma volume is decreased
Relative Polycythemia
• Diminished plasma volume
o Dehydration and shock
• Spurious polycythemia
o Stress polycythemia
o Gaisbock’s syndrome
Absolute Polycythemia
• Secondary polycythemia with appropriately increased EPO production
o Decreased oxygen loading:
§ Hypoxia
§ High altitude
§ Pulmonary disease
§ Cyanotic heart disease
§ Carboxyhemoglobinemia
§ Hb M
o Decreased oxygen Unloading:
§ High oxygen affinity hemoglobinopathy
§ Diphosphoglycerate deficiency
• Secondary polycythemia with Inappropriately increased EPO production
o Neoplasm
§ Wilms’ tumor
§ Renal carcinoma
§ Cerebellar hemangioma
§ Hepatoma
o Localized tissue hypoxia
§ Polycystic kidney
§ Renal artery stenosis
o Post-renal transplant
o Acute hepatitis
• Genetic Polycythemia
o Primary familial congenital polycythemia
§ Mutated EPO receptor
o Chuvash polycythemia
§ Mutated VHL gene
 • Primary marrow disorder
o Polycythemia Vera

Polycythemia Vera
Introduction:
• According to WHO has classified MPNs into four predominant Disorder
o Chronic myeloid Leukemia (CML)
o Polycythemia vera (PV)
§ 2.5 per 100, 000 persons
o Thrombocythemia (ET)
o Primary myelofibrosis (PMF)
• PV - Polycythemia vera
• AKA: Polycythemia Rubra Vera
• Panmyelosis
• Manifested by erythrocytosis, leukocytosis, and thrombocytosis of vary degree
• 90%-97 of the patient with PV
o JAK2 V617F mutation
• Hallmark: Plethora

Incidence:
• Rarely children
• Ages of 40 to 60 years
o Most often appear/occurs
o Peak incidence after 60 years old
• Occurs more often in men than women

Clinical features:
• Thrombocytosis, leukocytosis or splenomegaly
o Initial Manifestation of PV
• Erythrocytosis
o Cause hyperviscosity lead to Neurologic symptoms
o Vertigo, headache, and Transient Ischemic Attack (TIA)
• Hypertension
o Red cell mass elevation
• Eryhromelalgia
o Syndrome associated with Thrombocytosis
o Involved your lower extremities and erythema
• Splenomegaly and hepatomgaly
o Can be seen
• Aquagenic pruritus
o Common complaint
o Intense itching after exposure to water
Pathogenic Mechanism:
• Neoplastic Clonal stem cell are hypersensitive
o Function independently to erythropoietin (EPO) for cell growth
o Increase level of your EPO lead to stimulate of colony-forming growth system (CFG)
• Consistent mutation in JAK2 gene
o JAK 2 protein
§ Tyrosine kinase enzymes
§ Associated cytokine receptors -> when bind to ligand -> JAK2 protein will be
activated
§ Undergo phosphorylation -> SIGNAL TRANSDUCERS AND ACTIVATION
OF TRANSCRIPTION (STAT) protein
§ Bind promoter regions and signal gene expression
• STAT5, STAT3, MAP kinase, PI3k/AKT
• STAT protein
o Activated transcriptions factor
o Activate gene designed to drive and control
§ Proliferation and differentiation while also initiating
apoptosis
§ Activates BCL-C (anti-apoptotic)
§ Lead to cell accumulation

Laboratory Procedures:
• Phlebotomy
o Prompt and effective reduction of the red cell mass and blood volume
o Goal: Induced a state of Iron Deficiency with normal HB concentration Suppress
erythrocytosis
o Patient with PV need to achieve the Iron-Deficient state
§ Phlebotomy interval will be 3-Months
o 42% - 44% Men and 39% - 42% for women
§ To maintained the normal range of hematocrit
• Cytoreductive Therapy
o Cytoreductive therapy should be considered in patients at high risk for thrombotic events
§ Non-alkylating myelosuppressive agent
• Hydroxyurea - cytoreductive agent of choice for PV
• 500mg (once or twice daily)
• Reduced the following:
o Leukocyte
o Erythrocytes
o Platelet counts
§ Recombinant human interferon-alpha
• Pegylated interferon-alpha - decrease the expression of the JAK2
V617F
• Induce responses at molecular level than controlling abnormal blood
count
§ JAK2 inhibitor Ruxolitinib
• Also improved quality of life in PV patient
• 10 mg two time daily
§ PIImatinib mesylate
• Selective Tyrosine kinase inhibitor
• Goal: decrease blood count and splenomegaly
§ Anagrelide
 • Phosphodiesterase inhibitor
• Platelet aggregating agent which reduce the platelet count
§ Splenectomy
• Late stage of disease
• When your spleen become massive and cause early satiety and weight
loss
o Severe anaemia or thrombocytopenia

References:
• Tefferi, A., Vannucchi, A. M., & Barbui, T. (2018). Polycythemia vera treatment algorithm 2018. Blood
cancer journal, 8(1), 3.
• CHAIN, N. O. V. B. G. (2020). Rodak's Hematology: Clinical Principles and Applications. Platelets, 19,
11-5.
• Carr, J. H. (2021). Clinical Hematology Atlas-E-Book: Clinical Hematology Atlas-E-Book. Elsevier Health
Sciences.