Polycythemia

1. PolycythemiaPolycythemia

2. IntroductionIntroduction
Polycythemia vera is a chronic Polycythemia vera is a chronic
myeloproliferative disorder characterized myeloproliferative disorder characterized
by increased red blood cell mass (RCM), by increased red blood cell mass (RCM),
or erythrocytosis or erythrocytosis
The resultant hyperviscosity of the blood The resultant hyperviscosity of the blood
predisposes such patients to thrombosis predisposes such patients to thrombosis

3. IntroductionIntroduction
Increased RCM is accompanied by Increased RCM is accompanied by
increased white blood cell (myeloid) and increased white blood cell (myeloid) and
platelet (megakaryocytic) production, platelet (megakaryocytic) production,
which is due to an abnormal clone of the which is due to an abnormal clone of the
hematopoietic stem cells with increased hematopoietic stem cells with increased
sensitivity to the different growth factors sensitivity to the different growth factors
for maturation. for maturation.

4. Its etiology is not fully established, but Its etiology is not fully established, but
hypersensitivity to interleukin-3 may play a hypersensitivity to interleukin-3 may play a
role in the sustained erythrocytosis role in the sustained erythrocytosis
observed in this disease. observed in this disease.
IntroductionIntroduction

5. IntroductionIntroduction
Polycythemia vera should be suspected in Polycythemia vera should be suspected in
patients with elevated hemoglobin or patients with elevated hemoglobin or
hematocrit levels, splenomegaly, or portal hematocrit levels, splenomegaly, or portal
venous thrombosis. venous thrombosis.

6. IntroductionIntroduction
Secondary causes of increased red blood Secondary causes of increased red blood
cell mass (e.g., heavy smoking, chronic cell mass (e.g., heavy smoking, chronic
pulmonary disease, renal disease) are pulmonary disease, renal disease) are
more common than polycythemia vera and more common than polycythemia vera and
must be excluded must be excluded

7. IntroductionIntroduction
Patients may present with complaints of pruritus Patients may present with complaints of pruritus
after bathing, burning pains in the distal after bathing, burning pains in the distal
extremities (erythromelalgia), gastrointestinal extremities (erythromelalgia), gastrointestinal
disturbances, or nonspecific complaints such as disturbances, or nonspecific complaints such as
weakness, headaches, or dizziness. weakness, headaches, or dizziness.
Other patients are diagnosed after an incidental Other patients are diagnosed after an incidental
finding of an elevated hemoglobin and/or finding of an elevated hemoglobin and/or
hematocrit level on a complete blood count. hematocrit level on a complete blood count.

8. IntroductionIntroduction
Diagnosis is made using criteria Diagnosis is made using criteria
developed by the Polycythemia Vera developed by the Polycythemia Vera
Study Group; major criteria include Study Group; major criteria include
elevated red blood cell mass, normal elevated red blood cell mass, normal
oxygen saturation, and palpable oxygen saturation, and palpable
splenomegaly. splenomegaly.

9. IntroductionIntroduction
Untreated patients may survive for six to Untreated patients may survive for six to
18 months, whereas adequate treatment 18 months, whereas adequate treatment
may extend life expectancy to more than may extend life expectancy to more than
10 years. 10 years.

10. IntroductionIntroduction
Treatment includes phlebotomy with the Treatment includes phlebotomy with the
possible addition of myelosuppressive possible addition of myelosuppressive
agents based on a risk-stratified agents based on a risk-stratified
approach. approach.
Agents under investigation include Agents under investigation include
interferon alfa-2b, anagrelide, and aspirin. interferon alfa-2b, anagrelide, and aspirin.
Consultation with a hematologist is Consultation with a hematologist is
recommended.recommended.

11. IntroductionIntroduction
Alternative Names:Alternative Names:
Primary polycythemia Primary polycythemia
Polycythemia rubra veraPolycythemia rubra vera
Myeloproliferative disorderMyeloproliferative disorder
ErythremiaErythremia
Splenomegalic polycythemiaSplenomegalic polycythemia
Vaquez's diseaseVaquez's disease
Osler's diseaseOsler's disease
Polycythemia with chronic cyanosisPolycythemia with chronic cyanosis
Myelopathic polycythemiaMyelopathic polycythemia
Erythrocytosis megalosplenicaErythrocytosis megalosplenica
Cryptogenic polycythemia Cryptogenic polycythemia

12. PathophysiologyPathophysiology
Normal stem cells are present in the bone Normal stem cells are present in the bone
marrow of patients with PV. marrow of patients with PV.
Also present are abnormal clonal stem Also present are abnormal clonal stem
cells that interfere with or suppress normal cells that interfere with or suppress normal
stem cell growth and maturation. stem cell growth and maturation.

13. Evidence indicates that the etiology of Evidence indicates that the etiology of
panmyelosis is unregulated neoplastic panmyelosis is unregulated neoplastic
proliferation. proliferation.
The origin of the stem cell transformation The origin of the stem cell transformation
remains unknownremains unknown
PathophysiologyPathophysiology

14. Polycythemia veraPolycythemia vera
Bone marrow film at 100X magnification Bone marrow film at 100X magnification
demonstrating hypercellularity and demonstrating hypercellularity and
increased number of megakaryocytes increased number of megakaryocytes

15. PathophysiologyPathophysiology
Thromboses and bleeding are frequent in Thromboses and bleeding are frequent in
persons with PV and myeloproliferative persons with PV and myeloproliferative
disease (MPD), and they result from the disease (MPD), and they result from the
disruption of hemostatic mechanisms disruption of hemostatic mechanisms
because of because of
an increased level of red blood cells an increased level of red blood cells
an elevation of the platelet countan elevation of the platelet count

16. Tissue factor is also synthesized by blood Tissue factor is also synthesized by blood
leukocytes, the level of which is increased leukocytes, the level of which is increased
in persons with MPD, which can contribute in persons with MPD, which can contribute
to thrombosis. to thrombosis.
PathophysiologyPathophysiology

17. Hyperhomocystinemia is a risk factor for Hyperhomocystinemia is a risk factor for
thrombosis and is also widely prevalent in thrombosis and is also widely prevalent in
patients with MPD (35% in controls, 56% patients with MPD (35% in controls, 56%
in persons with PV). in persons with PV).
PathophysiologyPathophysiology

18. Polycythemia vera is a rare diseasePolycythemia vera is a rare disease
The peak incidence of PV is age 50-70 The peak incidence of PV is age 50-70
yearsyears
However, it occurs in persons of all age However, it occurs in persons of all age
groups, including those in early adulthood and groups, including those in early adulthood and
childhood, albeit rarely. childhood, albeit rarely.
The disease is slightly more common in The disease is slightly more common in
males than in females.males than in females.
StatisticsStatistics

19. The disease usually develops slowlyThe disease usually develops slowly
Symptoms are often insidious in onsetSymptoms are often insidious in onset
They are often related to blood hyperviscosity They are often related to blood hyperviscosity
secondary to a marked increase in the cellular secondary to a marked increase in the cellular
elements of blood, which impairs elements of blood, which impairs
microcirculation. microcirculation.
HistoryHistory

20. Symptoms are related to hyperviscosity, Symptoms are related to hyperviscosity,
sludging of blood flow, and thromboses, sludging of blood flow, and thromboses,
which lead to poor oxygen delivery and which lead to poor oxygen delivery and
symptoms that include:symptoms that include:
headache, dizziness, vertigo, tinnitus, visual headache, dizziness, vertigo, tinnitus, visual
disturbances, angina pectoris, or intermittent disturbances, angina pectoris, or intermittent
claudications claudications
HistoryHistory

21. Bleeding complications ,, include Bleeding complications ,, include
epistaxis, gum bleeding, ecchymoses, and epistaxis, gum bleeding, ecchymoses, and
GI bleeding.GI bleeding.
Thrombotic complications ,, include Thrombotic complications ,, include
venous thrombosis or thromboembolism venous thrombosis or thromboembolism
and an increased prevalence of stroke and an increased prevalence of stroke
and other arterial thromboses.and other arterial thromboses.
HistoryHistory

22. Abdominal pain due to peptic ulcer Abdominal pain due to peptic ulcer
disease is present because PV is disease is present because PV is
associated with increased histamine levels associated with increased histamine levels
and gastric acidity or possible Budd-Chiari and gastric acidity or possible Budd-Chiari
syndrome (hepatic portal vein thrombosis) syndrome (hepatic portal vein thrombosis)
or mesenteric vein thrombosis. or mesenteric vein thrombosis.
HistoryHistory

23. Splenomegaly, when present, can cause Splenomegaly, when present, can cause
early satiety because of early satiety because of
gastric filling being impaired by the enlarged gastric filling being impaired by the enlarged
spleen or, rarely, symptoms of splenic spleen or, rarely, symptoms of splenic
infarction. infarction.
Weight loss may result from early satiety Weight loss may result from early satiety
or from the increased myeloproliferative or from the increased myeloproliferative
activity of the abnormal clone. activity of the abnormal clone.
HistoryHistory

24. Pruritus results from increased histamine Pruritus results from increased histamine
levels released from increased basophils levels released from increased basophils
and mast cells and can be exacerbated by and mast cells and can be exacerbated by
a warm bath or shower. a warm bath or shower.
This occurs in up to 40% of patients. This occurs in up to 40% of patients.
HistoryHistory

25. The following symptoms are due to the The following symptoms are due to the
manifestations of myeloproliferative manifestations of myeloproliferative
disorders with extramedullary disorders with extramedullary
hematopoiesis:hematopoiesis:
Splenomegaly - Present in 75% of patients at Splenomegaly - Present in 75% of patients at
the time of diagnosisthe time of diagnosis
Hepatomegaly - Present in approximately Hepatomegaly - Present in approximately
30% of patients with PV30% of patients with PV
PhysicalPhysical

26. Hypertension is common in patients with Hypertension is common in patients with
PV. The red blood cell mass should PV. The red blood cell mass should
differentiate PV from Gaisbock syndrome, differentiate PV from Gaisbock syndrome,
which is hypertension and which is hypertension and
pseudopolycythemia (ie, high hemoglobin pseudopolycythemia (ie, high hemoglobin
levels due to low plasma volume). levels due to low plasma volume).
PhysicalPhysical

27. Polycythemia is characterized by Polycythemia is characterized by
increased cell counts in all cell lines in the increased cell counts in all cell lines in the
myeloid series (ie, red blood cells, white myeloid series (ie, red blood cells, white
blood cells [preferentially granulocytes], blood cells [preferentially granulocytes],
and platelets). and platelets).
PhysicalPhysical

28. However, if red blood cell levels are increased, However, if red blood cell levels are increased,
several conditions must be excluded, including:several conditions must be excluded, including:
conditions that increase red blood cells secondary to conditions that increase red blood cells secondary to
systemic hypoxic conditions or an artificial condition systemic hypoxic conditions or an artificial condition
stimulating Epo secretion in the kidneysstimulating Epo secretion in the kidneys
granulocytosis from infections or mobilization by granulocytosis from infections or mobilization by
secondary causes, as in leukemoid reactionssecondary causes, as in leukemoid reactions
thrombocytosis from bleeding and iron deficiency. thrombocytosis from bleeding and iron deficiency.
PhysicalPhysical

29. Secondary Causes of Increased Secondary Causes of Increased
Red Cell Mass (Erythrocytosis)Red Cell Mass (Erythrocytosis)
Chronic pulmonary or cardiac disease Chronic pulmonary or cardiac disease
Decreased 2,3-diphosphoglycerate Decreased 2,3-diphosphoglycerate
High oxygen affinity hemoglobinopathy High oxygen affinity hemoglobinopathy
Increased carboxyhemoglobin (in smokers) and Increased carboxyhemoglobin (in smokers) and
methemoglobin methemoglobin
Residence at high altitude Residence at high altitude
Adrenal cortical hypersecretion Adrenal cortical hypersecretion
Hydronephrosis Hydronephrosis
Tumors producing erythropoietin or anabolic steroids Tumors producing erythropoietin or anabolic steroids
Relative (stress) Relative (stress)
Disorders associated with decreased plasma volume Disorders associated with decreased plasma volume
(e.g., diarrhea, emesis, renal diseases) (e.g., diarrhea, emesis, renal diseases)

30. DiagnosisDiagnosis
PV should be suspected when PV should be suspected when
hemoglobin and/or hematocrit levels are hemoglobin and/or hematocrit levels are
elevatedelevated
(> than 18 g per dL [180 g per L] in white men (> than 18 g per dL [180 g per L] in white men
and > than 16 g per dL [160 g per L] in blacks and > than 16 g per dL [160 g per L] in blacks
and women)and women)
hematocrit level greater than 52 percent hematocrit level greater than 52 percent
(0.52) in white men and 47 percent (0.47) (0.52) in white men and 47 percent (0.47)
in blacks and women in blacks and women

31. DiagnosisDiagnosis
PV also should be suspected in patients PV also should be suspected in patients
with portal venous thrombosis and with portal venous thrombosis and
splenomegaly with or without splenomegaly with or without
thrombocytosis and leukocytosis.thrombocytosis and leukocytosis.

32. Diagnosis: Diagnosis: Other Signs and Symptoms of Other Signs and Symptoms of
Polycythemia VeraPolycythemia Vera
More CommonMore Common
Hematocrit level >52 percent Hematocrit level >52 percent
(0.52) in white men, >47 (0.52) in white men, >47
percent (0.47) in blacks and percent (0.47) in blacks and
women women
Hemoglobin level >18 g per dL Hemoglobin level >18 g per dL
(180 g per L) in white men, (180 g per L) in white men,
>16 g per dL (160 g per L) in >16 g per dL (160 g per L) in
blacks and women) blacks and women)
Plethora Plethora
Pruritus after bathing Pruritus after bathing
Splenomegaly Splenomegaly
Weight loss Weight loss
Weakness Weakness
Sweating Sweating
Less CommonLess Common
Bruising/epistaxis Bruising/epistaxis
Budd-Chiari syndrome Budd-Chiari syndrome
Erythromelalgia Erythromelalgia
Gout Gout
Hemorrhagic events Hemorrhagic events
Hepatomegaly Hepatomegaly
Ischemic digits Ischemic digits
Thrombotic events Thrombotic events
Transient neurologic Transient neurologic
complaints (headache, tinnitus, complaints (headache, tinnitus,
dizziness, blurred vision, dizziness, blurred vision,
paresthesias) paresthesias)
Atypical chest pain Atypical chest pain

34. In making the diagnosis of PV, once a In making the diagnosis of PV, once a
secondary cause is ruled out, the secondary cause is ruled out, the
diagnosis of PV is made using a diagnosis of PV is made using a
combination of major and minor criteria combination of major and minor criteria
defined by the Polycythemia Vera Study defined by the Polycythemia Vera Study
Group (PVSG). Group (PVSG).
Although new diagnostic modalities have Although new diagnostic modalities have
been developed, these criteria remain the been developed, these criteria remain the
standard method to diagnose PV standard method to diagnose PV
DiagnosisDiagnosis

35. A diagnosis of polycythemia vera is made when a patent fulfillsA diagnosis of polycythemia vera is made when a patent fulfills
all three of the major criteriaall three of the major criteria
OrOr
any two major and any two minor criteriaany two major and any two minor criteria
Major Criteria Major Criteria
total RBC vol total RBC vol
Men > or = to 36 mL/kgMen > or = to 36 mL/kg
Women > or = to 32 mL/kgWomen > or = to 32 mL/kg
arterial 02 saturation > or = to 92% arterial 02 saturation > or = to 92%
Splenomegaly Splenomegaly
Minor Criteria Minor Criteria
Thrombocytosis with platelet count > 400,000/mL Thrombocytosis with platelet count > 400,000/mL
Leukocytosis with WBC > 12,000/mL Leukocytosis with WBC > 12,000/mL
Increased leukocyte alkaline phosphatase LAP > 100U/L (no infection) Increased leukocyte alkaline phosphatase LAP > 100U/L (no infection)
Serum B12 > 900 pg/mL or binding capacity UB12 BC > 2200 pg/mL Serum B12 > 900 pg/mL or binding capacity UB12 BC > 2200 pg/mL

36. Serum Epo assaySerum Epo assay
Epo levels in patients with PV are often Epo levels in patients with PV are often
below the lower limit of normal compared below the lower limit of normal compared
with patients with secondary with patients with secondary
erythrocytosis and pseudoerythrocytosiserythrocytosis and pseudoerythrocytosis
but the levels for PV and secondary but the levels for PV and secondary
erythrocytosis or pseudoerythrocytosis erythrocytosis or pseudoerythrocytosis
overlap and are nonspecific for differentiating overlap and are nonspecific for differentiating
these conditions. these conditions.

37. Bone marrow morphology and Bone marrow morphology and
histologyhistology
Overall hypercellularity with expansion of all cell Overall hypercellularity with expansion of all cell
lines with megakaryocytic proliferation and the lines with megakaryocytic proliferation and the
presence of myelofibrosis can help diagnose PV presence of myelofibrosis can help diagnose PV
and MPDand MPD
PV patients may have normal bone marrow PV patients may have normal bone marrow
findingsfindings
These results are nonspecific and may be These results are nonspecific and may be
observed in the other Philadelphia observed in the other Philadelphia
chromosome–negative MPDs. chromosome–negative MPDs.

38. Bone marrow findings for Bone marrow findings for
Polycythemia vera include Polycythemia vera include
Moderate to marked hypercellularity Moderate to marked hypercellularity
trilineage hyperplasia trilineage hyperplasia
megakaryocytes increased; megakaryocytes increased;
hyperlobulated hyperlobulated
dilated sinusoids with intravascular dilated sinusoids with intravascular
hematopoiesis hematopoiesis
decreased or absent iron stores decreased or absent iron stores
increased reticulin (only in a minority of increased reticulin (only in a minority of
patients) patients)

39. LabsLabs
Peripheral blood findings Peripheral blood findings
Increased hemoglobin & hematocrit Increased hemoglobin & hematocrit
Normal red blood cell morphology, unless iron Normal red blood cell morphology, unless iron
deficient or spent phasedeficient or spent phase
Normoblasts may be present Normoblasts may be present
Mild to moderate leukocytosis Mild to moderate leukocytosis
Mild neutrophilia and/or basophilia Mild neutrophilia and/or basophilia
Thrombocytosis Thrombocytosis

40. This disease may also alter the results of the This disease may also alter the results of the
following tests: following tests:
Lactate dehydrogenase Lactate dehydrogenase
u/a u/a
Serum uric acid Serum uric acid
T- wbc T- wbc
RBC count RBC count
Platelet aggregation test Platelet aggregation test
Leukocyte alkaline phosphatase Leukocyte alkaline phosphatase
Hemoglobin Hemoglobin
ESRESR
Erythropoietin Erythropoietin
LabsLabs

41. Automated red blood cell counts and hematocrit values Automated red blood cell counts and hematocrit values
(including hemoglobin levels) may be deceptive with (including hemoglobin levels) may be deceptive with
regard to the total red blood cell mass. regard to the total red blood cell mass.
Direct measurement of the red blood cell mass should Direct measurement of the red blood cell mass should
show an increase with a normal or slightly decreased show an increase with a normal or slightly decreased
plasma volume. plasma volume.
This is a nuclear medicine test that uses radiochromium-labeled This is a nuclear medicine test that uses radiochromium-labeled
red blood cells to measure actual red blood cell and plasma red blood cells to measure actual red blood cell and plasma
volume. volume.
However, patients with hemoglobin concentrations of at However, patients with hemoglobin concentrations of at
least 20 g/dL or hematocrit values of at least 60% in least 20 g/dL or hematocrit values of at least 60% in
males and 56% in females always have an elevated red males and 56% in females always have an elevated red
blood cell mass. blood cell mass.
LabsLabs

42. The red blood cells in patients with PV are The red blood cells in patients with PV are
usually normochromic normocytic unless usually normochromic normocytic unless
the patient has been bleeding from the patient has been bleeding from
underlying peptic ulcer disease or underlying peptic ulcer disease or
phlebotomy treatment (wherein the cells phlebotomy treatment (wherein the cells
may be hypochromic and microcytic, may be hypochromic and microcytic,
reflecting low iron stores). reflecting low iron stores).
LabsLabs

43. An elevated white blood cell count (>12,000/µL) An elevated white blood cell count (>12,000/µL)
occurs in approximately 60% of patients. It is occurs in approximately 60% of patients. It is
mainly composed of neutrophils with a left shift mainly composed of neutrophils with a left shift
and a few immature cells.and a few immature cells.
Mild basophilia occurs in 60% of patients.Mild basophilia occurs in 60% of patients.
The leukocyte alkaline phosphatase score is elevated The leukocyte alkaline phosphatase score is elevated
(>100 U/L) in 70% of patients. (>100 U/L) in 70% of patients.
This technique is only semiquantitative and is This technique is only semiquantitative and is
susceptible to laboratory errors unless it can be susceptible to laboratory errors unless it can be
performed by flow cytometry, which is not routinely performed by flow cytometry, which is not routinely
availableavailable
LabsLabs

44. The platelet count is elevated to The platelet count is elevated to
400,000-800,000/mL in approximately 400,000-800,000/mL in approximately
50% of patients. 50% of patients.
LabsLabs

45. The release of potassium into the serum The release of potassium into the serum
caused by the increased number of caused by the increased number of
platelets during in vitro coagulation may platelets during in vitro coagulation may
cause a pseudohyperkalemia in the cause a pseudohyperkalemia in the
serum, while the true plasma potassium serum, while the true plasma potassium
level in vivo is actually within the reference level in vivo is actually within the reference
range, as shown by measuring plasma range, as shown by measuring plasma
levels and the lack of ECG changes. levels and the lack of ECG changes.
LabsLabs

46. Abnormal platelet function (as measured Abnormal platelet function (as measured
by platelet aggregation tests with by platelet aggregation tests with
epinephrine, adenosine diphosphate, or epinephrine, adenosine diphosphate, or
collagen) may be demonstrated, but collagen) may be demonstrated, but
bleeding time may be normal. bleeding time may be normal.
Some patients' platelet-rich plasma Some patients' platelet-rich plasma
aggregates spontaneously without the aggregates spontaneously without the
addition of any of the above substances. addition of any of the above substances.
This indicates a propensity for thromboses This indicates a propensity for thromboses
LabsLabs

47. Bone marrow studies are not necessary to Bone marrow studies are not necessary to
establish the diagnosis but the findings of:establish the diagnosis but the findings of:
hypercellularityhypercellularity
hyperplasia of the erythroid, granulocytic and hyperplasia of the erythroid, granulocytic and
megakaryocytic cell linesmegakaryocytic cell lines
myelofibrosis myelofibrosis
support the diagnosis of a support the diagnosis of a
myeloproliferative process. myeloproliferative process.
LabsLabs

48. Iron stores are decreased or absent Iron stores are decreased or absent
because of the increased red blood cell because of the increased red blood cell
mass, and macrophages may be masked mass, and macrophages may be masked
in the myeloid hyperplasia that is present. in the myeloid hyperplasia that is present.
LabsLabs

49. Fibrosis is increased and detected early Fibrosis is increased and detected early
by silver stains for reticulin by silver stains for reticulin
LabsLabs

50. Cytogenetics of the bone marrow cells Cytogenetics of the bone marrow cells
show a clonal abnormality in show a clonal abnormality in
30% of patients who are not treated and in 30% of patients who are not treated and in
50% of patients who are treated with 50% of patients who are treated with
alkylating or myelosuppressive agents.alkylating or myelosuppressive agents.
These chromosomal abnormalities include These chromosomal abnormalities include
deletions of the long arm of chromosome 5 or 20 deletions of the long arm of chromosome 5 or 20
(5q-, 20q-) and trisomy 8 (+8) or 9 (+9).(5q-, 20q-) and trisomy 8 (+8) or 9 (+9).
Leukemic transformation is usually associated with Leukemic transformation is usually associated with
multiple or complex abnormalities.multiple or complex abnormalities.
LabsLabs

51. Hyperuricemia occurs in 40% of patients Hyperuricemia occurs in 40% of patients
and reflects the high turnover rate of bone and reflects the high turnover rate of bone
marrow cells releasing DNA metabolites. marrow cells releasing DNA metabolites.
LabsLabs

52. Imaging StudiesImaging Studies
An enlarged spleen is often palpable and An enlarged spleen is often palpable and
does not require any imaging studies. does not require any imaging studies.
In some patients with posteriorly enlarged In some patients with posteriorly enlarged
spleens or in those who are obese, spleens or in those who are obese,
ultrasonography or CT scanning may be ultrasonography or CT scanning may be
able to detect an enlargement missed able to detect an enlargement missed
during the physical examination.during the physical examination.

53. Other TestsOther Tests
The serum Epo level should be decreased The serum Epo level should be decreased
in nearly all patients with PV and no recent in nearly all patients with PV and no recent
hemorrhage. hemorrhage.
This distinguishes polycythemia from This distinguishes polycythemia from
secondary causes of polycythemia in secondary causes of polycythemia in
which the serum Epo level is generally which the serum Epo level is generally
within the reference range or is elevated. within the reference range or is elevated.
Each lab has its own reference range for Each lab has its own reference range for
serum Epo level serum Epo level

54. TreatmentTreatment
The objective of treatment is to reduce the The objective of treatment is to reduce the
high blood viscosity (thickness of the high blood viscosity (thickness of the
blood) due to the increased red blood cell blood) due to the increased red blood cell
mass and to prevent hemorrhage and mass and to prevent hemorrhage and
thrombosis. thrombosis.
No single treatment is available for PV. No single treatment is available for PV.
Thrombosis accounts for the majority of Thrombosis accounts for the majority of
morbidity and mortality. The major goal of morbidity and mortality. The major goal of
treatment is to prevent thrombotic events. treatment is to prevent thrombotic events.

55. Examples of thrombotic events include Examples of thrombotic events include
arterial and venous thrombosis, arterial and venous thrombosis,
cerebrovascular accident, deep venous cerebrovascular accident, deep venous
thrombosis, myocardial infarction, thrombosis, myocardial infarction,
peripheral arterial occlusion, and peripheral arterial occlusion, and
pulmonary infarctpulmonary infarct
TreatmentTreatment

56. TreatmentTreatment
The mainstay of treatment for PV is The mainstay of treatment for PV is
phlebotomy, which is aimed at reducing phlebotomy, which is aimed at reducing
hyperviscosity by decreasing the venous hyperviscosity by decreasing the venous
hematocrit level to less than 45 percent hematocrit level to less than 45 percent
(0.45) in white men and 42 percent (0.42) (0.45) in white men and 42 percent (0.42)
in blacks and women.in blacks and women.
The PVSG reported the best median The PVSG reported the best median
survival, 12.6 years, for this type of survival, 12.6 years, for this type of
treatment. treatment.

57. Phlebotomy is a simple procedure without Phlebotomy is a simple procedure without
many risks, except for the eventual many risks, except for the eventual
development of iron deficiency development of iron deficiency

58. TreatmentTreatment
Patients with hematocrit values of less Patients with hematocrit values of less
than 70% may be bled twice a week to than 70% may be bled twice a week to
reduce the hematocrit to the range of reduce the hematocrit to the range of
40%. 40%.
Patients with severe plethora who have Patients with severe plethora who have
altered mentation or associated vascular altered mentation or associated vascular
compromise can be bled more vigorously, compromise can be bled more vigorously,
with daily removal of 500 mL of whole with daily removal of 500 mL of whole
bloodblood

59. Elderly patients with some cardiovascular Elderly patients with some cardiovascular
compromise or cerebral vascular compromise or cerebral vascular
complications should have the volume complications should have the volume
replaced with saline solution after each replaced with saline solution after each
procedure to avoid postural hypotension procedure to avoid postural hypotension
TreatmentTreatment

60. Because phlebotomy is the most efficient Because phlebotomy is the most efficient
method of lowering the hemoglobin and method of lowering the hemoglobin and
hematocrit levels to the reference range, all new hematocrit levels to the reference range, all new
patients are initially phlebotomized to decrease patients are initially phlebotomized to decrease
the risk of complications. the risk of complications.
The presence of elevated platelet counts that The presence of elevated platelet counts that
may be exacerbated by the phlebotomy is an may be exacerbated by the phlebotomy is an
indication to use myelosuppressive agents to indication to use myelosuppressive agents to
avoid thrombotic or hemorrhagic complications avoid thrombotic or hemorrhagic complications
TreatmentTreatment

61. Once the patient's hemoglobin and Once the patient's hemoglobin and
hematocrit values are reduced to within hematocrit values are reduced to within
the reference range (ie, <45%), implement the reference range (ie, <45%), implement
a maintenance program either by inducing a maintenance program either by inducing
iron deficiency by continuous iron deficiency by continuous
phlebotomies (frequency of the procedure phlebotomies (frequency of the procedure
depends on the rate of reaccumulation of depends on the rate of reaccumulation of
red blood cells) or using a red blood cells) or using a
myelosuppressive agent. myelosuppressive agent.
TreatmentTreatment

62. TreatmentTreatment
The use of myelosuppressive agents such as radioactive The use of myelosuppressive agents such as radioactive
phosphorus (32P), chlorambucil (Leukeran), busulfan phosphorus (32P), chlorambucil (Leukeran), busulfan
(Myleran), pipobroman (Vercyte), and hydroxyurea (Myleran), pipobroman (Vercyte), and hydroxyurea
(Hydrea) in conjunction with phlebotomy has been (Hydrea) in conjunction with phlebotomy has been
studied. studied.
Chlorambucil, busulfan, and pipobroman, all alkylating Chlorambucil, busulfan, and pipobroman, all alkylating
agents, have fallen out of favor because of concerns agents, have fallen out of favor because of concerns
about rates of iatrogenic leukemia.about rates of iatrogenic leukemia.
The agent 32P remains in use with supplemental The agent 32P remains in use with supplemental
phlebotomy and has a reported median survival similar phlebotomy and has a reported median survival similar
to that of phlebotomy alone-10.9 years according to to that of phlebotomy alone-10.9 years according to
PVSG data. PVSG data.

63. In patients treated with chlorambucil and In patients treated with chlorambucil and
32P the PVSG demonstrated a decreased 32P the PVSG demonstrated a decreased
survival rate and increased mortality rate survival rate and increased mortality rate
from acute leukemia in the first 5 years, from acute leukemia in the first 5 years,
and a total of 17% of patients had and a total of 17% of patients had
leukemia after 15 years with. leukemia after 15 years with.
TreatmentTreatment

64. Hydroxyurea has been the mainstay Hydroxyurea has been the mainstay
therapy for PV after the PVSG results therapy for PV after the PVSG results
indicated it is an effective agent for indicated it is an effective agent for
myelosuppression; however, concerns myelosuppression; however, concerns
have been raised regarding long-term have been raised regarding long-term
risks for leukemic transformation. risks for leukemic transformation.
In the PVSG trial, HU therapy reduced the In the PVSG trial, HU therapy reduced the
risk of thrombosis compared with risk of thrombosis compared with
phlebotomy alone phlebotomy alone
TreatmentTreatment

65. TreatmentTreatment
Recombinant interferon alfa-2b reduces Recombinant interferon alfa-2b reduces
myeloproliferation and splenomegaly, and alleviates the myeloproliferation and splenomegaly, and alleviates the
symptom of pruritus.symptom of pruritus.
It has no established mutagenic potential, and thus may It has no established mutagenic potential, and thus may
prove a valuable option for younger patients and those prove a valuable option for younger patients and those
with significant splenomegaly. with significant splenomegaly.
A small case series of 11 patients found that the patients' A small case series of 11 patients found that the patients'
red cell indices could be normalized over six to 12 red cell indices could be normalized over six to 12
months with interferon therapy alone, and without months with interferon therapy alone, and without
evidence of thrombosis.evidence of thrombosis.
However, many patients discontinue interferon because However, many patients discontinue interferon because
of side effects, and high cost of treatment. of side effects, and high cost of treatment.

66. TreatmentTreatment
splenectomy in patients with painful splenectomy in patients with painful
splenomegaly or repeated episodes of splenomegaly or repeated episodes of
thrombosis causing splenic infarction thrombosis causing splenic infarction

67. TreatmentTreatment
Occasionally, chemotherapy may be given Occasionally, chemotherapy may be given
to suppress the bone marrow.to suppress the bone marrow.
The use of anti-platelet therapy (such as The use of anti-platelet therapy (such as
aspirin) is controversial because it may aspirin) is controversial because it may
cause gastric bleeding.cause gastric bleeding.
Allopurinol is given for hyperuricemia Allopurinol is given for hyperuricemia
(gout).(gout).

68. TreatmentTreatment
A risk-stratified approach to the management of A risk-stratified approach to the management of
PV is currently recommended PV is currently recommended
Patients treated with phlebotomy alone benefit Patients treated with phlebotomy alone benefit
from low rates of malignancy but experience from low rates of malignancy but experience
more thrombosis events during the first few more thrombosis events during the first few
years of treatment. years of treatment.
Patients treated with myelosuppressive agents Patients treated with myelosuppressive agents
and supplemental phlebotomy avoid this early and supplemental phlebotomy avoid this early
thrombotic risk but in turn have significant rates thrombotic risk but in turn have significant rates
of malignant transformation after about six years of malignant transformation after about six years
of therapy of therapy

69. High-risk patients High-risk patients
those 60 years or olderthose 60 years or older
or those with a history of thrombosis or those with a history of thrombosis
A myelosuppressive agent with supplemental A myelosuppressive agent with supplemental
phlebotomy is reasonable in this groupphlebotomy is reasonable in this group
This group's generally shorter life expectancy lessens This group's generally shorter life expectancy lessens
the threat of eventual iatrogenic malignancy. the threat of eventual iatrogenic malignancy.
Patients in this group stand to gain from the benefit of Patients in this group stand to gain from the benefit of
lower early thrombosis rates with myelosuppressive lower early thrombosis rates with myelosuppressive
medications. medications.
TreatmentTreatment

70. Indeterminate riskIndeterminate risk
< than age 60 and have no history of < than age 60 and have no history of
thrombocytosis, but do have cardiovascular or thrombocytosis, but do have cardiovascular or
other risk factorsother risk factors
Therapy in this group should be Therapy in this group should be
individualized, possibly with the addition of individualized, possibly with the addition of
agents acting on platelet function or agents acting on platelet function or
number. number.
TreatmentTreatment

71. low risk low risk
< than 60 years and have no thrombosis-< than 60 years and have no thrombosis-
related risk factorsrelated risk factors
Phlebotomy alone may be the treatment of Phlebotomy alone may be the treatment of
choice with the goal of reducing the choice with the goal of reducing the
hematocrit level to less than 45 percent hematocrit level to less than 45 percent
(0.45) or lower based on gender and race(0.45) or lower based on gender and race
TreatmentTreatment

72. Consultation with a hematologist is Consultation with a hematologist is
recommended to apply such strategies, recommended to apply such strategies,
and newer agents may be tailored to and newer agents may be tailored to
patients on an individualized basis. patients on an individualized basis.
TreatmentTreatment

73. PrognosisPrognosis
Polycythemia vera usually develops Polycythemia vera usually develops
slowly, and most patients treated slowly, and most patients treated
appropriately do not experience any appropriately do not experience any
problems related to the disease. problems related to the disease.
However, the abnormal bone marrow cells However, the abnormal bone marrow cells
may begin to grow uncontrollably leading may begin to grow uncontrollably leading
to acute myelogenous leukemia.to acute myelogenous leukemia.

74. PrognosisPrognosis
Patients with polycythemia vera also have Patients with polycythemia vera also have
an increased tendency to form blood clots an increased tendency to form blood clots
that can result in strokes or heart attacks. that can result in strokes or heart attacks.
Some patients may experience abnormal Some patients may experience abnormal
bleeding because their platelets are bleeding because their platelets are
abnormal.abnormal.

75. PrognosisPrognosis
PV is a chronic disease, and its natural PV is a chronic disease, and its natural
history of 1.5-3 years of median survival in history of 1.5-3 years of median survival in
the absence of therapy has been the absence of therapy has been
extended to at least 10-20 years because extended to at least 10-20 years because
of new therapeutic tools. of new therapeutic tools.

76. The major causes of morbidity and The major causes of morbidity and
mortality are as follows:mortality are as follows:
ThrombosisThrombosis
Hemorrhagic complicationsHemorrhagic complications
Peptic ulcer diseasePeptic ulcer disease
Myelofibrosis and pancytopeniaMyelofibrosis and pancytopenia
Acute leukemia or a myelodysplastic Acute leukemia or a myelodysplastic
syndrome syndrome
PrognosisPrognosis

77. ThrombosisThrombosis
reported in 15-60% of patients reported in 15-60% of patients
major cause of death in 10-40% of major cause of death in 10-40% of
patientspatients
Venous and arterial thromboses have Venous and arterial thromboses have
resulted in pulmonary emboli, renal failure resulted in pulmonary emboli, renal failure
from renal vein or artery thrombosis, from renal vein or artery thrombosis,
intestinal ischemia from mesenteric vein intestinal ischemia from mesenteric vein
thromboses, or peripheral arterial emboli. thromboses, or peripheral arterial emboli.

78. Hemorrhagic complicationsHemorrhagic complications
occur in 15-35% of patientsoccur in 15-35% of patients
lead to death in 6-30% of these patientslead to death in 6-30% of these patients
Bleeding is usually the consequence of Bleeding is usually the consequence of
vascular compromise resulting from vascular compromise resulting from
ischemic changes from thrombosis or ischemic changes from thrombosis or
hyperviscosity. hyperviscosity.

79. Peptic ulcer diseasePeptic ulcer disease
Associated with PV at a 3 to 5 fold higher Associated with PV at a 3 to 5 fold higher
rate than that of the general populationrate than that of the general population
This has been attributed to increased This has been attributed to increased
histamine serum levels histamine serum levels

80. Myelofibrosis and pancytopeniaMyelofibrosis and pancytopenia
Occur in 3-10% of patients, usually late in Occur in 3-10% of patients, usually late in
the disease the disease
In these patients, infections and bleeding In these patients, infections and bleeding
complications may be the most serious complications may be the most serious
health threatshealth threats
red blood cell transfusions may be red blood cell transfusions may be
required to maintain adequate red blood required to maintain adequate red blood
cell counts and to improve fatigue and cell counts and to improve fatigue and
other anemia-related symptoms. other anemia-related symptoms.

81. Acute leukemia or a Acute leukemia or a
myelodysplastic syndromemyelodysplastic syndrome
Develops in 1.5% of patients treated with Develops in 1.5% of patients treated with
phlebotomy alonephlebotomy alone
The transformation risks The transformation risks
increase to 13.5% within 5 years with treatment using increase to 13.5% within 5 years with treatment using
chlorambucil chlorambucil
And 10.2% within 6-10 years in patients treated with And 10.2% within 6-10 years in patients treated with
32P32P
At 15 years, the transformation risk for HU is At 15 years, the transformation risk for HU is
5.9%, which, although not statistically significant, 5.9%, which, although not statistically significant,
is a worrisome trend is a worrisome trend

82. QuestionsQuestions