eMedicine Specialties > Hematology > Stem Cells and Disorders

Polycythemia Vera: Follow-up

Author: Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Coauthor(s): Ulrich Woermann, MD, Consulting Staff, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland
Contributor Information and Disclosures

Updated: Jan 23, 2009

Follow-up

Further Inpatient Care

• The optimum management of polycythemia vera (PV) remains elusive despite the findings of the PVSG. However, certain diseases, such as familial erythrocythemia, secondary polycythemia, and relative polycythemia (benign condition), should be differentiated, and the exact diagnosis of PV should be established.
• General principles in the management of polycythemia vera (PV) include the following:
  • Tailor therapy to suit the clinical needs of the patient. Consider the status of the formed elements of the blood, bone marrow, and organomegaly.
  • Normalize red blood cell mass with phlebotomy as rapidly as clinically possible (250-500 mL every other day). Patients who are elderly or cardiovascularly compromised should be phlebotomized cautiously, and smaller amounts should be removed.
  • Suppress myeloproliferative activity with chemotherapy (HU) in all patients older than 50 years. In general,³² P should be reserved for patients older than 80 years or patients with comorbid conditions in whom life expectancy is less than 5-10 years and the convenience of³² P dosing outweighs the substantial risks of developing acute leukemia 5-15 years after³² P administration. Patients with thrombotic tendencies or those who develop thrombocytosis following phlebotomy should be treated with marrow suppression. Consider anagrelide in younger patients (aged 50-70 y).
  • Maintain blood values at reference range levels by regular examination and treatment.
  • Avoid overtreatment and toxicity by careful and judicious use of chemotherapy and radiation. Supplemental phlebotomy is preferred over excess marrow suppression.
  • Postpone elective surgery until long-term control of the disease is established.
  • Women of childbearing age should only be treated with phlebotomies. In young males, myelosuppressive therapy can lead to aspermia; thus evaluate treatment carefully before using any chemotherapy or radiotherapy.
  • The PVSG no longer recommends the use of alkylating agents because of the associated increased incidence of leukemia and certain types of cancer.
  • Treat hyperuricemia with allopurinol (100-300 mg/d) until remission has been attained. For acute gouty attacks, colchicine or other anti-inflammatory agents are indicated (see Gout).

Further Outpatient Care

• Thrombosis in polycythemia vera (PV) is substantially more frequent in patients treated with phlebotomy alone without myelosuppression. This risk is believed to be related to thrombocytosis, which was not observed in the study. Platelet numbers alone are not likely to be the primary factor responsible for the increased risk of thrombosis; the presence of abnormal platelets is more likely.
• The initial PVSG study using antiplatelet drugs also used aspirin at 300 mg 3 times a day plus dipyridamole at 75 mg 3 times a day. This showed an increase in the incidence of hemorrhage. Lower doses of aspirin have been suggested to be more effective without increasing bleeding complications, although this has not yet been demonstrated in a prospective randomized trial.
• A syndrome specific to polycythemia vera (PV) and other MPDs is termed erythromelalgia, and it is associated with an increased risk of thrombosis. The symptoms are burning pain in the feet, hands, and digits, sometimes associated with pallor, erythema, or cyanosis of the distal portions of the extremities. Occasionally, it may progress to frank gangrene. In some instances, this is treated with aspirin (50-300 mg/d) and dipyridamole (75 mg orally 3 times a day).Myelosuppressive therapy plus phlebotomies, with the intent of normalizing the erythrocyte and platelet counts, also decreases or eliminates these symptoms. Proven thrombotic complications warrant the use of long-term anticoagulation with warfarin (see below).
  

  

  This blood film at 10,000X magnification shows a giant platelet and an eosinophil. Erythrocytes show signs of hypochromia as a result of repeated phlebotomies. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.

  [ CLOSE WINDOW ]

  

  This blood film at 10,000X magnification shows a giant platelet and an eosinophil. Erythrocytes show signs of hypochromia as a result of repeated phlebotomies. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.

Complications

• Bleeding complications (1%) in patients with polycythemia vera (PV) include epistaxis, gum bleeding, ecchymoses, and GI bleeding.
• Thrombotic complications (1%) include venous thrombosis or thromboembolism and an increased prevalence of stroke and other arterial thromboses.
• In young patients and during pregnancy, interferon alfa may be useful when HU is unsuitable. Anagrelide may be useful when interferon alfa is not tolerated.
• In the very elderly patients for whom regular clinic attendance is impractical,³² P or intermittent busulfan may still be used.

Prognosis

• Polycythemia vera (PV) is a chronic disease, and its natural history of 1.5-3 years of median survival in the absence of therapy has been extended to at least 10-20 years because of new therapeutic tools. The major causes of morbidity and mortality are as follows:
• Thrombosis has been reported in 15-60% of patients, depending on the control of their disease. It is the major cause of death in 10-40% of patients. Venous and arterial thromboses have resulted in pulmonary emboli, renal failure from renal vein or artery thrombosis, intestinal ischemia from mesenteric vein thromboses, or peripheral arterial emboli.
• Hemorrhagic complications occur in 15-35% of patients and lead to death in 6-30% of these patients. Bleeding is usually the consequence of vascular compromise resulting from ischemic changes from thrombosis or hyperviscosity.
• Peptic ulcer disease is reported to be associated with polycythemia vera (PV) at a 3- to 5-fold higher rate than that of the general population. This has been attributed to increased histamine serum levels.
• Myelofibrosis and pancytopenia occur in 3-10% of patients, usually late in the disease, which is considered the spent phase of polycythemia vera (PV). In these patients, infections and bleeding complications may be the most serious health threats, and red blood cell transfusions may be required to maintain adequate red blood cell counts and to improve fatigue and other anemia-related symptoms.
• Acute leukemia or a myelodysplastic syndrome develops in 1.5% of patients treated with phlebotomy alone. The transformation risks increase to 13.5% within 5 years with treatment using chlorambucil and to 10.2% within 6-10 years in patients treated with³² P. At 15 years, the transformation risk for HU is 5.9%, which, although not statistically significant, is a worrisome trend.

Miscellaneous

Medicolegal Pitfalls

• Make the proper diagnosis, distinguishing polycythemia vera (PV) from secondary erythrocytosis. Myelosuppressive therapy is not indicated and may be dangerous in patients with secondary causes. Pure erythrocytosis that occurs in families may be secondary to an altered oxygen-hemoglobin dissociation curve (high oxygen affinity in hemoglobin M). Do not administer myelosuppressive agents to these patients.
• Failure to diagnose or to treat polycythemia vera (PV) to maintain the erythrocyte and platelet counts in the reference range subjects a patient to a high risk of thrombotic problems, which may be lethal or disabling, and a moderate risk of significant bleeding problems.
• Inappropriate and unjustified use of alkylating agents or³² P in patients for whom better alternatives are available (eg, HU, anagrelide, interferon alfa) may subject a patient to an inordinately high risk of developing acute leukemia over the next 5-15 years.
• Elective surgery in patients with uncontrolled polycythemia vera (PV) results in an extremely high risk of thrombotic complications.

Special Concerns

• The finding that HU may have a late effect in increasing the rate of transformation to acute leukemia after 15 years raises concern for patients aged 50-70 years or younger, because these patients may easily receive more than 15 years of therapy. However, this remains controversial because most studies show no significantly increased risk of transformation to acute leukemia with HU therapy and because the major study that showed a slightly increased risk included patients who also had received alkylating agents in the past.
• Investigate other agents such as anagrelide and interferon alfa for efficacy and long-term safety.

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