Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 13-24: Polycythemia Vera + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Autonomous overproduction of erythroid cells Elevated RBC mass Hematocrit > 49% in males or > 48% in females JAK2 V617F mutation Splenomegaly Normal arterial oxygen saturation Usually elevated white blood count and platelet count +++ General Considerations ++ Although characterized by autonomous overproduction of erythroid cells, there is overproduction of all hematopoietic cell lines +++ Demographics ++ 60% of patients are men Median age at presentation is 60 years Rarely occurs in persons under age 40 years + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Common complaints related to expanded blood volume and increased blood viscosity include Headache Dizziness Tinnitus Blurred vision Fatigue Generalized pruritus is related to histamine release from basophils Epistaxis is probably related to engorgement of mucosal blood vessels in combination with abnormal hemostasis Thrombosis Appears to be related both to increased blood viscosity and abnormal platelet function Incidence of thrombotic complications of surgery is very high if polycythemia is uncontrolled; elective surgery should be deferred until the condition has been treated Increased bleeding can also occur Physical examination reveals plethora and engorged retinal veins +++ Differential Diagnosis ++ Spurious polycythemia may be related to diuretic use or may occur without obvious cause Suspect secondary causes of polycythemia if Splenomegaly is absent Elevated hematocrit is not accompanied by increases in other cell lines Secondary causes of polycythemia include Hypoxia: cardiac disease, pulmonary disease, high altitude Carboxyhemoglobin: smoking Kidney lesions Erythropoietin-secreting tumors (rare) Abnormal hemoglobins (rare) Polycythemia vera should be differentiated from other myeloproliferative disorders (Table 13–14) ++Table Graphic Jump LocationTable 13–14.Laboratory features of myeloproliferative neoplasms.View Table||Download (.pdf) Table 13–14. Laboratory features of myeloproliferative neoplasms. White Count Hematocrit Platelet Count Red Cell Morphology Polycythemia vera N or ↑ ↑↑ N or ↑ N Essential thrombocytosis N or ↑ N ↑↑ N Primary myelofibrosis N or ↓ or ↑ ↓ ↓ or N or ↑ Abn Chronic myeloid leukemia ↑↑ N or ↓ N or ↑ or ↓ N Abn, abnormal; N, normal. + Diagnosis Download Section PDF Listen +++ +++ Laboratory Findings ++ Hematocrit (at sea level) that exceeds 49% in males or 48% in females RBCs RBC morphology is normal at presentation (Table 13–14) However, microcytosis, hypochromia, and poikilocytosis may result from iron deficiency following treatment by phlebotomy RBC mass is elevated White blood cells Usually normal morphology, though basophilia and eosinophilia are frequently present Count is usually elevated to 10,000–20,000/mcL Platelets Morphology is usually normal Count is variably increased, sometimes to counts exceeding 1,000,000/mcL Erythropoietin levels are suppressed Bone marrow Hypercellular, with hyperplasia of all hematopoietic elements Iron stores are usually absent Vitamin B12 levels are strikingly elevated because of increased levels of transcobalamin III Overproduction of uric acid may lead to hyperuricemia Progressive hypersplenism may also lead to elliptocytosis Confirm diagnosis with JAK2 mutation testing + Treatment Download Section PDF Listen +++ ++ Phlebotomy is treatment of choice One unit of blood (approximately 500 mL) is removed weekly until the hematocrit is < 45% Hematocrit is maintained at < 45% by repeated phlebotomy as necessary Avoid medicinal iron supplementation A diet low in iron-containing foods is not necessary but will increase the intervals between phlebotomies Indications for myelosuppressive therapy High phlebotomy requirement Thrombocytosis Intractable pruritus Hydroxyurea Used for patients in whom phlebotomy is problematic and when myelosuppressive therapy is indicated Usual dose is 500–1500 mg/day orally, adjusted to keep platelets < 500,000/mcL without reducing the neutrophil count to < 2000/mcL Ruxolitinib JAK2 inhibitor Approved by FDA for patients resistant to or intolerant or hydroxyurea Associated with greater benefit for both hematocrit control without phlebotomy (60%) and splenic volume reduction (38%) Symptom burden improved by greater than 50% in 49% of patients Pegylated alfa-2 interferon Has demonstrated considerable efficacy, with hematologic response rates > 80%, as well as molecular responses in 20% (as measured by JAK2 mutations) Patients failing to achieve molecular responses had a higher frequency of mutations outside the JAK2 pathway and were more likely to acquire new mutations during therapy Side effects were generally acceptable and much less significant than with nonpegylated forms of interferon Low-dose aspirin (75–81 mg/day orally) Has been shown to reduce the risk of thrombosis without excessive bleeding Should be part of therapy for all patients without contraindications to aspirin Avoid alkylating agents because of increased risk of conversion to acute leukemia Lastly, a new and promising therapeutic strategy is induction of apoptosis via the p53 pathway through pharmacologic inhibition of human double minute 2 (mdm2) + Outcome Download Section PDF Listen +++ +++ Complication ++ Peptic ulcer disease +++ Prognosis ++ Median survival of > 15 years Arterial thrombosis is major cause of morbidity and mortality Over time, polycythemia vera may convert to myelofibrosis or to chronic myeloid leukemia (CML) In approximately 5% of cases, the disorder progresses to acute myeloid leukemia (AML), which is usually refractory to therapy +++ When to Refer ++ Patients with polycythemia vera should be referred to a hematologist +++ When to Admit ++ Inpatient care is rarely required + References Download Section PDF Listen +++ + +Barbui T et al. The 2016 revision of WHO classification of myeloproliferative neoplasms: clinical and molecular advances. Blood Rev. 2016 Nov;30(6):453–9. [PubMed: 27341755] + +Gerds AT. Beyond JAK-STAT: novel therapeutic targets in Ph-negative MPN. Hematology Am Soc Hematol Educ Program. 2019 Dec 6;2019(1):407–14. [PubMed: 31808852] + +Tefferi A et al. Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management. Am J Hematol. 2019;94:133–43. [PubMed: 30281843]