Polycythemia (Rubra) Vera
DX | RX
See also Polycythemia /
A clonal cell hematologic malignant disorder with excessive erythroid, myeloid
and megakaryocytic elements in the bone marrow. It is one of a group of
Predominant age: Middle to late years, mean is 60 years (range 15-90).
Predominant sex: Male > Female (slightly)
SYMPTOMS: Early stages may produce no symptoms
flushing, headache, dizziness, tinnitus, visual disturbances, pruritus, dyspnea,
lassitude, or weakness.
Headache- 48%, Weakness- 47%, Pruritis- 43% [A common
complaint is intense itching after exposure to water (most typically in a
bath or shower)--the so-called "aquagenic pruritus." This may be the initial
presentation of PV, and is reported in up to 60% of PV patients under the
age of 40], Dizziness- 43%, Diaphoresis- 33%, Visual
disturbances- 31%, Weight loss- 29%, Paresthesias- 29%,
Dyspnea- 26%, Joint symptoms- 26%, Epigastric discomfort-
Splenomegaly-70%; Hepatomegaly- 40%, Skin
plethora/erythema-67%, Conjunctival plethora-59%,
Engorged vessels in the optic fluid- 46%, Systolic BP>140 mm Hg-
72%, Diastolic BP>90 mm Hg- 32%
Polycythemia with elevated Hgb, Hct, platelet counts, WBC, uric acid;
decreased erythropoietin, bone marrow erythroid
hyperplasia, increased leukocyte alkaline
phosphatase, increased vit.B12 level, decreased folic acid level,
elevated alk.phosphatase & conjungated bilirubin, hypercalcemia.
Bone marrow aspiration (red cell hyperplasia, absent iron stores)
and biopsy (fibrosis during spent phase of the disease)
Drugs that may alter lab results: Diuretics may cause a spurious
Disorders that may alter lab results: Excessive use of alcohol or tobacco
Diagnosis of Polycthemia
Vera (Study Group Diagnostic Criteria and Their
DX: M1 + M2 +M3, or M1 + M2 + any 2 from m1-4
M1. Red Cell Mass: Male >36 ml/mg, Female >32 ml/kg
Identifies actual polycythemia vs. spurious
M2. Arterial O2 saturation>92%
Rules out most common etiology of secondary
Evidence of a myeloproliferative state.
m1. Thrombocytosis >400,000 /µL
m2. Leukocytosis >12,000 /µL
m3. Leukocyte alkaline phosphatase activity >100 (no fever or infection)
m4. Serum B12 (>900 pg/ml) or unsaturated B12 binding capacity (>2200
The diagnosis of PV requires the presence of all three major criteria (M)
or the first two major criteria and two minor criteria (m). The first major
criterion provides confirmation that the patient has actual polycythemia,
as indicated by an elevated red cell mass. The second major criterion rules
out the most common etiology of secondary polycythemia, severe arterial
hypoxemia, by demonstrating a normal or only moderately reduced arterial
oxygen saturation. The third criterion, evidence of a myeloproliferative
syndrome, is provide either by the third major criterion, splenomegaly, or
by two of the four minor criteria.
Individualized management necessary. Dependent on many factors - age, disease
duration, disease phenotype, complications, disease activity.
Currently, phlebotomy is mainstay of
Beyond that, differences exist among authorities about use and effectiveness
Phlebotomy: To reduce hematocrit to approximately 45%. Performed as
often as every 2 or 3 days until normal hematocrit reached. Phlebotomies
of 250-500 m/L. Reduce to 250-350 m/L in elderly patients or patients with
cardiovascular disease. Phlebotomy repeated as necessary for maintenance.
If patient cannot tolerate phlebotomy - chemotherapy (hydroxyurea is the
least mutagenic agent) or radiation therapy.
Phlebotomy offers prompt and effective reduction of the red cell mass and
blood volume to normal values. Many patients can be maintained in an essentially
normal state by phlebotomy together with a few simple adjuvants, when necessary,
to control hyperuricemia or pruritus.
Concomitant therapy possibilities, e.g., some form of myelosuppression,
radioactive phosphorus (in elderly patients)
Pruritus therapy:cyproheptadine, (4 mg three or four times per day)
Manage thrombotic or hemorrhagic complications the same as with nonpolycythemic
Uric acid reduction therapy
Allopurinol 300 mg/day for uric acid reduction
Cyproheptadine for pruritus, 4-16 mg as needed
Radioactive phosphorous 32P in selected cases:
In patients with PV, 32 P induces satisfactory clinical and hematologic
remissions that may last years   . The fall in the red cell count
usually does not begin until 30 to 60 days from the time 32 P is given.
Therefore, initial phlebotomy may be indicated for symptomatic control. As
with any myelosuppressive agent, care must be taken to avoid producing anemia,
leukopenia, or thrombocytopenia. A usual dose is 3 to 5 millicuries
(mCi) of 32 P, intravenously, or 2.3 mCi/M2. 32 P is effective and
easily tolerated therapy. Survival after treatment is reported to be 10 to
14.5 years. The principal drawback to 32 P therapy is the increased incidence
of acute leukemia.
Busulfan or alkylating agents (e.g., hydroxyurea):
Busulphan and chlorambucil are two alkylating agents that were widely
used in PV, but the increased frequency of leukemia observed with alkylating
agents led to a discontinuation of their routine use.
The nonalkylating myelosuppressive agent hydroxyurea is the
chemotherapeutic agent most widely used in PV at present. Its efficacy in
controlling erythrocyte, leukocyte, and platelet counts in PV has been clearly
demonstrated . Thrombotic complications are less common than are observed
in patients treated with phlebotomy only. Hydroxyurea permits rapid reduction
of leukocyte and platelet counts; supplemental phlebotomy may occasionally
be necessary to reduce the red cell mass. As a rule, neutropenia or
thrombocytopenia will correct rapidly following cessation or reduction of
hydroxyurea dose; for the same reason, however, missing a few days of therapy
may be associated with recurrence of leukocytosis or thrombocytosis.
The use of low-dose aspirin is controversial in view of bleeding risk,
but small doses may be given if required.
There is no definite answer to the question of whether antiplatelet
therapy is beneficial in conjunction with phlebotomy.
Interferon is an emerging treatment: Recombinant human interferon
alpha is an agent that has also demonstrated efficacy in PV. One of these
studies compared phlebotomy to interferon therapy and reported that interferon
was more efficacious.
Anagrelide is a platelet-aggregating agent that is useful in the control
of thrombocytosis refractory to hydroxyurea or interferon in myeloproliferative
disorders such as PV.
Splenectomy is useful only as a palliative measure in the late stages
of the disease, when the spleen becomes massive and causes early satiety
and weight loss, severe anemia, or thrombocytopenia.
Summary and Recommendations for
Although treatment with phlebotomy, 32 P, or a variety of chemotherapeutic
agents is effective and prolongs survival, no modality is clearly the best
for everyone. The following recommendations represent a reasonable approach.
More detailed recommendations have been published by the Polycythemia
Vera Study Group
Most newly diagnosed patients should undergo
phlebotomy to obtain symptomatic control
of polycythemia. The rate and volume of phlebotomy is dictated by the patient's
clinical status, as outlined in the section on phlebotomy above. The hematocrit
should be reduced to the upper normal range (approximately 0.45).
The long-term therapy chosen to control PV varies according to the patient's
clinical status. Young patients (under 50) with no history of thrombosis
and without severe thrombocytosis (greater than 1000 × 103 /muL) can
probably be managed best with phlebotomy alone, with a target hematocrit
of 0.45. The addition of aspirin, 325 mg per day or less, may be beneficial,
although this is not proven at present. Patients with a history of thrombosis,
over the age of 70, or with severe thrombocytosis, should be treated with
myelosuppressive agents. Patients between the ages of 50 and 70 with no history
of thrombosis or severe thrombocytosis can be managed with
myelosuppressive agents or phlebotomy,
although the latter modality may increase their risk for thrombotic events.
The current myelosuppressive agent of choice is
hydroxyurea. Although the additional
risk of leukemia with longterm hydroxyurea therapy appears to be small, it
may not be zero  . 32P
may be useful in selected patients, in whom the potential leukemic
risks are outweighed by ease of administration and limitations imposed by
other clinical conditions. The role of
interferon in routine therapy of PV is
not established at present and merits further investigation.
Uric acid stones , Secondary gout
Vascular thromboses (major cause of death)
Transformation to leukemia
Increased risk for complications and mortality from surgery procedures.
Assess risk-benefits and assure optimal control of disorder before any elective
Median survival without treatment - 6 to 18 months following diagnosis
Survival up to 10 years with treatment
Some patients live, symptom-free, for 20 or more years
ASSOCIATED CONDITIONS: Budd-Chiari syndrome , Mesenteric artery thrombosis
Dambro: Griffith's 5-Minute Clinical Consult, 1999 ed.- Stanley G Smith
MA, MB, FCFPC
Lee: Wintrobe's Clinical Hematology, 10th ed., Copyright © 1999
Diagnosing polycythemia vera: a paradigm shift. Mayo Clin Proc
DxPlain - Mass. Gen. Hospital: http://dxplain.mgh.harvard.edu/dxp/dxp.pl
Williams WJ, Beutler E, Erslev AJ, et al, eds: Hematology. 4th Ed. New York,
Conley CL: Polycythemia vera, diagnosis and treatment. Hosp Practice 1987;
Berk PD, et al. Therapeutic recommendations in polycythemia vera based on
Polycythemia Vera Study Group protocols. Semin Hematol 1986;23:132.
Fruchtman SM, Wasserman LR. Therapeutic recomendations for polycythemia vera.
In: Wasserman LR, Berk PD, Berlin NI, eds. Polycythemia Vera and the
Myeloproliferative Syndromes. ed. Philadelphia: WB Saunders, 1995:337-350.