Polycythemia vera and essential thrombocythemia are chronic myeloproliferative diseases. The main goal of treatment in patients with these conditions is to prevent thrombo-hemorrhagic complications. Tefferi and colleagues reviewed the medical literature to summarize the pathogenesis, diagnosis and treatment of polycythemia vera and essential thrombocythemia.
Polycythemia vera can be diagnosed when a patient has all three major criteria (i.e., increased red blood cell mass [at least 36 mL per kg for men, at least 32 mL per kg for women]; normal arterial oxygen saturation [at least 92 percent]; and splenomegaly) or the first two major criteria plus any two of the minor criteria (i.e., platelet count of more than 400 × 103 per μL [400 × 109 per L]; leukocyte count of more than 12 × 103 per μL [.01 × 109 per L]; alkaline phosphatase level of more than 100 U per L; a vitamin B12 level of more than 900 pg per mL [664 pmol per L] or an unbound vitamin B12 binding capacity of more than 2,200 pg per mL [1,623 pmol per L]).
Men are more often affected by polycythemia vera than women, and about one fifth of patients present with a thrombotic event. Bleeding complications occur less frequently than thrombotic complications but are more likely in patients who are taking nonsteroidal anti-inflammatory agents. Other symptoms of polycythemia vera include headaches, transient neurologic or ocular complaints, and paresthesias. Pruritus after bathing may also occur. The risk of thrombosis does not correlate with the degree of thrombocytosis or the level of platelet function, although the number of patients analyzed in studies may not be large enough to show a correlation.
When phlebotomy was the sole treatment of polycythemia vera, the average rate of survival was extended to more than 12 years. Adding chlorambucil therapy to phlebotomy decreased the rate of survival to about nine years. Similarly, radioactive phosphorus plus phlebotomy decreased the rate of survival to less than 11 years. Patients who received these medications also had a higher risk of acquiring acute leukemia than those being treated with phlebotomy alone. However, chlorambucil and radioactive phosphorus were associated with a lower risk of thrombosis than treatment with phlebotomy alone. Patients taking hydroxyurea had lower incidences of early thrombosis and acute leukemia. Based on this information, the authors recommend that all patients with polycythemia vera be treated with phlebotomy (with goal hematocrit levels of less than 45 percent [0.45] in men and 42 percent [0.42] in women); patients at high risk for thrombosis should also receive hydroxyurea.
Essential thrombocythemia is diagnosed after reactive and clonal thrombocytosis are excluded. This can be done by measuring Creactive protein levels, erythrocyte sedimentation rates and fibrinogen levels. A bone marrow biopsy can rule out other chronic myeloid disorders. Women have essential thrombocythemia more often than men. Vasomotor symptoms such as headaches and paresthesias are more common, while thrombotic and bleeding events are progressively less common. There is a low incidence of transformation into acute leukemia or myelofibrosis with myeloid metaplasia. Prognosis is worse in patients older than 60 years and those who have a history of thrombosis. Qualitative or quantitative platelet abnormalities are not consistent predictors of thrombosis risk, although extreme thrombocytosis may be related to a higher incidence of gastrointestinal tract hemorrhage. The risk of thrombosis is reduced by the use of hydroxyurea (from 24 percent to less than 4 percent) and by keeping the platelet count less than 400 × 103 per μL (400 × 109 per L).
|Risk category||Age < 60 years||Age 60 years||Women of childbearing age|
|Low risk||Phlebotomy alone* or with low-dose aspirin‡||Not applicable||Phlebotomy alone† or with low-dose aspirin‡|
|Platelet count <1,500 × 103 per μL (1,500 × 109 per L)||Phlebotomy alone* or with interferon alfa,‡ low-dose aspirin,‡ or both||Not applicable||Phlebotomy alone† or with low-dose aspirin‡|
|Intermediate risk||Phlebotomy alone* or with interferon alfa§||Not applicable||Phlebotomy alone†|
|Platelet count >1,500 × 103 per μL|
|High risk||Phlebotomy plus hydroxyurea§ or interferon alfa§ plus low-dose aspirin‡||Phlebotomy plus hydroxyurea§ plus low-dose aspirin‡||Phlebotomy plus interferon alfa†§ plus low-dose aspirin‡|
In patients with polycythemia vera or essential thrombocythemia, vasomotor symptoms can be relieved with low-dose aspirin therapy (75 to 100 mg per day). However, use of aspirin should be avoided in patients with bleeding diathesis. The authors conclude that treatment of polycythemia vera or essential thrombocythemia should be directed by the presence of risk factors for thrombohemorrhagic complications. Treatment approaches for these disorders are outlined in Tables 1 and 2 on page 746.
|Risk category||Age < 60 years||Age ≥ 60 years||Women of childbearing age|
|Low risk||No treatment* or low-dose aspirin‡||Not applicable||No treatment† or low-dose aspirin‡|
|Intermediate risk||No treatment* or anagrelide‡ or low-dose aspirin‡||Not applicable||No treatment† or low-dose aspirin‡|
|Platelet count <1,500 × 103 per μL (1,500 × 109 per L)|
|Intermediate risk||No treatment† or anagrelide‡||Not applicable||No treatment†|
|Platelet count >1,500 × 103 per μL|
|High risk||Hydroxyurea§ or anagrelide* plus low-dose aspirin†||Hydroxyurea§ plus low-dose aspirin†||Interferon alfa|| plus low-dose aspirin†|