Polycythemia vera

Liane Chlus & Christina RiggallState University of New York Institute of Technology

Definition of the ProblemMyeloproliferative clonal disorder marked by increased production of red blood cells (erythrocytosis) with excessive erythroid, myeloid, and megakaryocytic elements in the bone marrow.

Morbidity and mortality are primarily related to complications from blood hyperviscosity as well as malignant transformation.

Synonym (s): primary polycythemia; Vaquez disease; Polycythemia, splenomegalic; vaquez-Osler disease Domino, 2014

Pathophysiology

Relative PolycythemiaDecrease in plasma volume while the total number of circulating erythrocytes remains the sameAlmost always caused by dehydration

Acute dehydration: vomiting, burns, crushing-type injuries and feversChronic dehydration: decreased oral fluid intake, cigarette smoking, long-term use of diuretics

(Dunphy, Winland-Brown, Porter & Thomas, 2011)

Pathophysiology

Absolute PolycythemiaThe actual numbers of circulating erythrocytes are increased with increase in measured RBC

Primary: chronic myeloproliferative disorder caused by an abnormally dividing pluripotential stem cell that leads to a clonal erythrocytosis that is erythropoietin independent, as well as a variable leukocytosis and thrombocytosis.Secondary: chronic hypoxia, carboxyhemoblobinemia, Cushing’s syndrome, chronic corticosteroid use, erythropoietin-secreting tumors, and cardiopulmonary diseases.

(Dunphy, Winland-Brown, Porter & Thomas, 2011)

EtiologyUnknown but thought to originate in a single cloneClonal proliferative disorder commonly associated with JAK2 V617F mutationGenetics:

JAK2V617F (tyrosine kinase mutation: Prevalance of 95 – 99%; is helpful in differentiating from secondary polycythemia. Homozygote carriers will have higher incidence of symptoms, such as pruritus, but will not have higher incidence of disease than heterozygotes.

(Dunphy, Winland-Brown, Porter & Thomas, 2011 and Domino, 2014)

Incidence

Predominant age: Middle to late years; mean is 60 years (range 15-90 years)

Predominant sex: Male>Female (slightly)

Incidence in the US: 1.9/100,000 person-year

Domino, 2014

Risk Factors

Ashkenazi Jewish ancestry (may have increased frequency)

Familial history (rare)

Domino, 2014

Clinical Findings

Patients may be asymptomatic or present with nonspecific complaints, such as fatigue, malaise, and subjective weakness, in early stagesErythromelalgia (burning pain of feet/hands, occasionally with erythema, pallor, cyanosis, or paresthesias)Spontaneous bruising/bleedingBone pain (ribs and sternum)Peptic ulcer disease (due to alterations in gastric mucosal blood flow)

Domino, 2014

Clinical FindingsPruritus after bathingCerebral circulation impairment

HeadacheTinnitusDizzinessVisual disturbanceTransient Ischemic Attack symptomsParesthesias

Other associated symptomsWeight Loss, Diaphoresis, Weakness, Fatigue

(Dunphy, Winland-Brown, Porter & Thomas, 2011)

Physical Exam

Bone tenderness (ribs and sternum)SplenomegalyHepatomegalyFacial plethoraSkin excoriations if significant pruritusGouty tophi or arthritisHypertension

Domino, 2014

Differential Diagnoses

Secondary polycythemiasHemoglobinopathyEctopic erythropoietin productionChronic myeloid leukemiaMyelofibrosisEssential Thrombocytosis

Domino, 2014

Polycythemia Vera

Primary Polycythemia

Chronic myeloproliferative disease

Secondary Polycythemia

Tobacco abuseRenal Cell CarcinomaChronic heart or lung diseaseMethemoglobinemiaLiving at high altitudeHydronephrosisAnabolic Steroid secreting tumorErythropoietin secreting tumorDecreased plasma volume (e.g. dehydration)

(Dunphy, Winland-Brown, Porter & Thomas, 2011)

Diagnosis

Exclude secondary causes of increased RBC CountLab Test:

CBC: Primary Secondary

HCT: >60% men/ >55% women

Elevated RBC WBC: between

10,000 and 20,000 Platelet elevated:

may exceed 1 million cells

Elevated RBC HCT may not be > 55 to 60% WBC lower Platelet counts lower

(Dunphy, Winland-Brown, Porter & Thomas, 2011)

DiagnosisOther Test to be performed:

Bone Marrow biopsy: Definitive diagnosis of polycythemia vera

Serum Erythropoietin: low in polycythemia vera and high in secondary polycythemia

(Dunphy, Winland-Brown, Porter & Thomas, 2011 & Passamonti, 2012)

Social/Environmental Considerations

Avoid high altitudesAlternate rest periods and activityUse electric razor: prevent accidental cutsBe aware of surrounding: minimize fallsQuit Smoking/avoid second hand smoke

(Diseases, 2009)

Management & Treatment Goal: Keep Hematocrit below threshold

White men: Hematocrit <45%Black patients and all women: Hematocrit <42%

Age Under 60 YearsLow or intermediate risk patients

Repeated phlebotomyInterferon alfa-2bLow dose Aspirin ( platelet count <150 x 10^3/uL)

High risk patientsLow or Intermediate Risk Management options (above)HydroxyureaBusulfan

(Moses, 2014)

Management & Treatment High Risk Patients over age 60 years

Repeated phlebotomyLow dose AspirinHydroxyureaBusulfan

Women of child bearing ageLow or intermediate risk patients

Repeated PhlebotomyLow Dose aspirin (platelet count <150 x 10^3/uL)

High Risk patientsLow or Intermediate Risk Management options (above)Interferon alfa-2bBisulfan

(Moses, 2014)

Therapeutic Phlebotomy

Phlebotomy is completed removing 250-500 mL of blood daily or every other day until HCT is between 40-45%In the elderly or people with cardiovascular disease 200-300mL is removed twice a weekAfter therapeutic level is reached, an H&H should be drawn every 4-8 weeks and subsequent treatments as needed.

Barbui, T., Finazzi, M., & Finazzi, G., 2012

Management & Treatment

PruitiusAntihistaminesParoxetineOatmeal bathInterferon alfa-2b

Prognosis: median survival in symptomatic patients

Survival without treatment: 6 – 18 MonthsSurvival with treatment: >10 years

(Moses, 2014)

ComplicationsUric acid stonesScondary goutVascular thrombosis (major cause of death)Transformation to leukemiaTransformation to myelofibrosisHemorrhagePeptic ulcerIncreased risk for complications and mortality from surgery procedures. Assess risk/benefits and ensure optimal control of disorder before any elective surgery

(Dunphy, Winland-Brown, Porter & Thomas, 2011)

Follow-upPatient Monitoring

Frequent monitoring during early treatment until target hematocrit is reachedMonitor hematocrit often and phlebotomize, as needed, to maintain target goal.

Diet Avoid iron supplements.

Patient Education Stress the importance of lifelong maintenance.Continuous education regarding possible complications and importance of seeking treatment early should complications appear

Domino, 2014

Counseling & Education

Absolute polycythemia reduces the lifespan, because of the risk of thrombosisStrict adherence to the treatment regimen is importantPatient should be aware of the signs and symptoms of DVT/PE, MI.Smoking cessation should be encouraged, patients who smoke have a much higher risk of arterial thrombotic event

Barbui, T., Finazzi, M., & Finazzi, G., 2012) (Dunphy, Winland-Brown, Porter & Thomas, 2011 and

Consultation & Referral

Refer to hematologist: for recommendations and co-managementDepending on CT/MRI results may need surgeon Carboxyhemoglobin levels noted may need pulmonologistWomen who want to get pregnant may need referral to a high-risk perinatal center

(Dunphy, Winland-Brown, Porter & Thomas, 2011)

Multiple Choice Questions1. Polycythemia is an increase in the production

of: A. Complete Blood CountB. Red Blood CountC. White Blood CountD. Differential Count

2. Which mutation is commonly associated with PolycethemiaA. PKU6V2JAKB. RQM12C. JAK2V617FD. JKP6

B

C

Multiple Choice Questions Cont.

3. The incidence of Polycythemia in the US isA. 1.9/100,000 personsB. 2.9/100,000C. 3.9/100,000D. 8.9/100,000

4. Which of the follow is a risk factor for PolycythemiaE. African AmericanF. MexicanG. LatinoH. Ashkenazi Jewish ancestry

A

D

Multiple Choice Questions Cont.5. Which of the following is not a clinical finding of Polycythemia

A. TinnitusB. Visual disturbanceC. Weight lossD. RLQ pain

6. On physical exam you may observe all of the following except

E. SplenomegalyF. Gouty tophi or arthritisG. HypertensionH. Hypotension

D

D

Multiple Choice Questions Cont.7. Secondary polycythemia includes

A. Daily ExerciseB. Tobacco abuseC. Vegetarian dietD. Drinking 64oz water daily

8. Hematocrit goal for management of a white man would include

E. Hematocrit >25%F. Hematocrit <45%G. Hematocrit >52%H. Hematocrit <55%

B

B

Multiple Choice Questions Cont.9. The test results which are used for definitive diagnosis of polycythemia vera

A. Bone Marrow BiopsyB. CBCC. CTD. MRI

10. What dietary advice is recommendedE. Avoid Vitamin DF. Avoid Calcium supplementG. Avoid Iron SupplementH. Take daily Iron Supplement

A

C

1. B: In diagnosing polycythemia, ordering a CBC will reveal an increase in RBC mass.2. C: In helping to differentiate between primary and secondary polycythemia, genetics could be tested and would result in a JAK2V617F mutation.3. A: According to Dunphy, Winland-Brown, Porter & Thomas (2011), the incidence of polycythemia in the US is 1.9/100,000person-year.4. D: Being of Ashkenazi Jewish ancestry may have an increased frequency to develop polycythemia (Dunphy, Winland-Brown, Porter & Thomas, 2011).5. D: RLQ pain is not a clinical finding of polycythemia.6. D: Hypotension will not likely be observed during the physical exam to diagnose polycythemia7. B: Tobacco abuse is a cause of secondary polycythemia.8. B: The goal of treatment for a white male is the Hematocrit <45%.9. A: The definitive diagnosis of polycythemia is a bone marrow biopsy.10. C: It is recommended to avoid Iron supplement if you have a diagnosis of polycythemia (Dunphy, Winland-Brown, Porter & Thomas, 2011).

References(2009). Diseases. (2nd ed., pp. 638-641). Ambler: Lippincott Williams & Wilkins.Antle, E. (2010). Who Needs a Therapeutic Phlebotomy?. Clinical Journal Of Oncology Nursing, 14(6), 694-696. doi:10.1188/10.CJON.694-696Barbui, T., Finazzi, M., & Finazzi, G. (2012). Front-line therapy in polycythemia vera and essential thrombocythemia. Blood

Reviews, 26(5), 205-211. doi:10.1016/j.blre.2012.06.002Domino, F.J. (2014). The 5-Minute Clinical Consult.. (22nd ed). Philadelphia: Lippincott, Williams & Wilkins. Dunphy, L., Winland-Brown, J., Porter, B., & Thomas, D. (2011). Primary Care The Art and Science of Advanced Practice

Nursing. (3rd ed., pp. 927-931). Philadelphia: F.A.Davis Company.Harrison, C. (2010). Rethinking disease definitions and therapeutic strategies in essential thrombocythemia and polycythemia

vera. Hematology / The Education Program Of The American Society Of Hematology. American Society Of Hematology. Education Program, 2010129-134. doi:10.1182/asheducation-2010.1.129

Khan, F., Khan, R., Iqbal, M., & Hussain, S. (2012). Polycythemia vera: Essential management protocols. Anaesthesia, Pain & Intensive Care, 16(1), 91-97.

Marchioli, R., Finazzi, G., Specchia, G., Cacciola, R., Cavazzina, R., Cilloni, D., & ... Rapezzi, D. (2013). Cardiovascular Events and Intensity of Treatment in Polycythemia Vera. New England Journal Of Medicine, 368(1), 22-33.

doi:10.1056/NEJMoa1208500Moses, S. (2014). Polycythemia rubra vera. Retrieved from http://fpnotebook.com/HemeOnc/Marrow/PlycythmRbrVr.htmNational Heart, Lung and Blood Institute. (2011). What is polycythemia vera? Retrieved from http://www.nhlbi.nih.gov/health/health-topics/topics/poly/Passamonti, F. (2012). How to manage polycythemia vera. Leukemia (08876924), 26(5), 870-874. doi:10.1038/leu.2011.334Reikvam, H., & Tiu, R. (2012). Venous thromboembolism in patients with essential thrombocythemia and polycythemia vera.

Leukemia (08876924), 26(4), 563-571. doi:10.1038/leu.2011.314