Therapeutic dilemmas: balancing the risks of bleeding, thrombosis, and leukemic transformation in myeloproliferative disorders (MPD).
With these uncertainties, which patients with ET and PV should receive myelosuppressive therapy and accept its possible risks? Remembering the generalization from the literature that most patients with ET who are to have a catastrophic thrombosis either have it at the time of diagnosis or after preceding, less severe thrombotic symptoms, it is acceptable to omit myelosuppressive therapy in asymptomatic patients with ET. Young patients with PV and no thrombotic manifestations can similarly be managed with phlebotomy alone. There is no evidence in the literature to show that myelosuppressive therapy should be used simply because the platelet count is high or to prevent transition to myeloid metaplasia. In patients with ET or PV with previous thrombotic manifestations, the risk/benefit ratio probably favors myelosuppressive therapy. The PVSG studies also suggest that patients over the age of 70 with PV are at particular risk for thrombosis and should be treated with myelosuppression. No myelosuppressive agent has been shown to be superior to hydroxyurea. Patients who fail on hydroxyurea should not be treated with 32P or alkylating agents. Anagrelide or interferon would be more appropriate. The PVSG-05 study suggests that high doses of aspirin, i.e. approximately 1.0 grams per day, are not indicated. Trials of low dose aspirin to prevent thrombosis are encouraged. There is no way to predict which patients will have hemorrhagic complications and, as mentioned, one study suggests that there will be few (44). Patients with thrombocytosis and pathological bleeding, i.e. hemorrhagic thrombocythemia, generally improve with myelosuppressive therapy. This syndrome is to be distinguished from patients who bleed with normal or low platelet counts, generally in the setting of myeloid metaplasia (14). These patients have an acquired disorder of platelet function due to platelet production from abnormal megakaryocytes. An occasional patient will benefit from increasing the platelet count by splenectomy.
Murphy
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Thomas Jefferson University, American Red Cross Blood Services, Penn-Jersey Region, Philadelphia, PA 19123, USA.
D002471:Cell Transformation, Neoplastic; D006470:Hemorrhage / Q000150:complications*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D009196:Myeloproliferative Disorders / Q000150:complications / Q000628:therapy*; D011087:Polycythemia Vera / Q000150:complications / Q000628:therapy; D018570:Risk Assessment; D013920:Thrombocythemia, Essential / Q000150:complications / Q000628:therapy; D013927:Thrombosis / Q000150:complications*