Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 4)

ComplicationsThe major clinical complications of PV relate directly to the increase in blood viscosity associated with red cell mass elevation and indirectly to the increased turnover of red cells, leukocytes, and platelets with the attendant increase in uric acid and cytokine production. The latter appears to be responsible for the increase in peptic ulcer disease and for the pruritus associated with this disorder, although formal proof for this has not been obtained. A sudden massive increase in spleen size can be associated with splenic infarction or progressive cachexia. Myelofibrosis appears to be part of the natural history of the...
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Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 4) Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 4) Complications The major clinical complications of PV relate directly to the increase inblood viscosity associated with red cell mass elevation and indirectly to theincreased turnover of red cells, leukocytes, and platelets with the attendantincrease in uric acid and cytokine production. The latter appears to be responsiblefor the increase in peptic ulcer disease and for the pruritus associated with thisdisorder, although formal proof for this has not been obtained. A sudden massiveincrease in spleen size can be associated with splenic infarction or progressivecachexia. Myelofibrosis appears to be part of the natural history of the disease butis a reactive, reversible process that does not itself impede hematopoiesis and byitself has no prognostic significance. In some patients, however, the myelofibrosisis accompanied by significant extramedullary hematopoiesis, hepatosplenomegaly,and transfusion-dependent anemia. The organomegaly can cause significantmechanical discomfort, portal hypertension, and cachexia. Although the incidenceof acute nonlymphocytic leukemia is increased in PV, the incidence of acuteleukemia in patients not exposed to chemotherapy or radiation is low, and thedevelopment of leukemia is related to older age but not disease duration,suggesting that the treatment exposure may be a more important risk factor thanthe disease itself. Erythromelalgia is a curious syndrome of unknown etiology associatedwith thrombocytosis, primarily involving the lower extremities and manifestedusually by erythema, warmth, and pain of the affected appendage and occasionallydigital infarction. It occurs with a variable frequency in myeloproliferativedisorder patients and is usually responsive to salicylates. Some of the centralnervous system symptoms observed in patients with PV, such as ocular migraine,may represent a variant of erythromelalgia. If left uncontrolled, erythrocytosis can lead to thrombosis involving vitalorgans such as the liver, heart, brain, or lungs. Patients with massive splenomegalyare particularly prone to thrombotic events because the associated increase inplasma volume masks the true extent of the red cell mass elevation as measured bythe hematocrit or hemoglobin level. A normal hematocrit or hemoglobin level ina PV patient with massive splenomegaly should be considered indicative of anelevated red cell mass until proven otherwise. Polycythemia Vera: Treatment PV is generally an indolent disorder whose clinical course is measured indecades, and its medical management should reflect its tempo. Thrombosis due toerythrocytosis is the most significant complication, and maintenance of thehemoglobin level at ≤140 g/L (14 g/dL; hematocrit therapy, but allopurinol should be administered to avoid further elevation of theuric acid when chemotherapy is employed to reduce splenomegaly or leukocytosisor to treat pruritus. Generalized pruritus intractable to antihistamines orantidepressants such as doxepin can be a major problem in PV; hydroxyurea,interferon α (IFN-α), and psoralens with ultraviolet light in the A range (PUVA)therapy are other methods of palliation. Asymptomatic thrombocytosis requires notherapy unless the platelet count is sufficiently high to cause an acquired form ofvon Willebrands disease due to proteolysis of high-molecular-weight vWFmultimers. Symptomatic splenomegaly can be treated with IFN-α. Although thedrug can be associated with significant side effects when used chronically, IFN-αreduces JAK2 V617F expression in PV patients, and its role in this disorder maybe expanding. Anagrelide, a phosphodiesterase inhibitor, can reduce the plateletcount and, if tolerated, is preferable to hydroxyurea because it lacks marrowtoxicity. A reduction in platelet number may be necessary in the treatment oferythromelalgia or ocular migraine if salicylates are not effective or the plateletcount is sufficiently high to cause an hemorrhagic diathesis. Alkylating agents andradioactive sodium phosphate (32P) are leukemogenic in PV, and their use shouldbe avoided. If a cytotoxic agent must be used, hydroxyurea is preferred, but thisdrug does not prevent either thrombosis or myelofibrosis in this disorder.Chemotherapy should be used for as short a time as possible. In some patients,massive splenomegaly unresponsive to reduction by hydroxyurea or IFN-α therapyand associated with intractable weight loss will require splenectomy. In somepatients with end-stage disease, pulmonary hypertension may develop due tofibrosis and extramedullary hematopoiesis. Allogeneic bone ma ...