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Polycythemia Rubra Vera
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Polycythemia Rubra Vera
, Polycythemia Vera
Definition
Excessive
Red Blood Cell
production due to chronic myeloproliferative neoplasm
Epidemiology
Men affected more than women
Age
Median age of onset: 60 years old
Under age 40 years old represent 20-25% of cases
Incidence
: 2.3 per 100,000 persons per year
Prevelance: 44-57 per 100,000 persons (U.S.)
Pathophysiology
Chronic myeloproliferative neoplasm (primary Polycythemia Vera)
Associated with
Janus Kinase
2 gene (JAK2) resulting in unregulated hematopoiesis
JAK2 V617F mutation (96% of polycythemia cases)
JAK2 exon 12 mutations (3% of polycythemia patients)
Primarily causes erythrocytosis
Also causes
Leukocytosis
and
Thrombocytosis
Excessive
Red Blood Cell
production (erythrocytosis)
Results in increased blood viscosity and
Blood Volume
Ultimately results in thrombosis
Causes
Primary Polycythemia
Chronic myeloproliferative neoplasm
Secondary Polycythemia
Tobacco Abuse
(Smoker's Polycythemia)
Renal Cell Carcinoma
Chronic heart or lung disease
Methemoglobinemia
Living at high altitude
Hydronephrosis
Anabolic Steroid
secreting tumor
Erythropoietin
secreting tumor
Decreased plasma volume (e.g.. dehydration)
Symptoms
Thrombotic event on presentation: 20-39% of cases
Cerebrovascular Accident
(CVA) or
Transient Ischemic Attack
(TIA)
Myocardial Infarction
Peripheral arterial thrombosis
Deep Vein Thrombosis
Portal Vein Thrombosis
or hepatic vein thrombosis (budd-chiari syndrome)
Constitutional symptoms
Fatigue
(88%)
Weight loss (31%)
Night Sweats
(52%)
Weakness
Fever
(18%)
Gene
ralized symptoms
Pruritus
(62%)
Gene
ralized burning, itching or
Paresthesia
s
Onset often within 10 minutes and lasting for up to 40 minutes after provocative exposure
Provoked by bathing, especially in warm water (
Aquagenic Pruritus
)
Also provoked by
Temperature
changes,
Alcohol
,
Exercise
Bone pain (50%)
Gout
history
Microvascular
Occlusion
symptoms
Headache
Tinnitus
Dizziness
Visual disturbance
Transient Ischemic Attack
symptoms
Distal
Paresthesia
s
Acrocyanosis
Erythromelalgia
(29% of cases)
Vasomotor findings with extremity congestion, redness, burning pain
Improves with
Aspirin
Splenomegaly
related symptoms
Abdominal Pain
Early satiety
Weight loss
Nausea
Signs
See complications below
Splenomegaly
(35-45% of patients, especially in advanced Polycythemia Vera)
Plethoric facies
Ruddy facial
Cyanosis
Eyes
Retina
l vein engorgement
Conjunctiva
l small vessel injection
Labs
Red Blood Cell
related increases
Elevated
Hemoglobin A
nd
Hematocrit
White men:
Hemoglobin
>18.5 mg/dl (
Hematocrit
>52%)
Black men:
Hemoglobin
>16 mg/dl (
Hematocrit
>47%)
Women: >16.5 mg/dl (
Hematocrit
>48%)
Elevated Red Blood Bell count
RBC Count
>36 ml/kg in men (>33 ml/kg in women)
Proliferation of other cell lines (50% of patients)
Platelet Count
(median): 400k/mm3
Leukocyte
count (median) 10.4k/mm3
Liver Function Test
s
LDH increased in 50% of patients
Diagnosis
Major Criteria (both required)
JAK2 V617F mutation, JAK2 exon 12 mutation or similar AND
Increased red cell mass
Precaution: May miss masked Polycythemia Vera who are JAK2+, but normal RBC mass
Men
Hemoglobin
>18.5 g/dl (WHO) or
Hematocrit
>52% (BCSH PVSG) or
RBC Count
>25% mean normal per WHO (e.g. >36 ml/kg)
Women
Hemoglobin
>16.5 g/dl (WHO) or
Hematocrit
>48% (BCSH PVSG) or
RBC Count
>25% mean normal per WHO (e.g. >33 ml/kg)
Minor Criteria (at least one required)
Endogenous erythroid colony formation in vitro (EPO-free medium)
Bone Marrow Biopsy
with hypercellularity for age
Trilineage growth (erythroid, granulocytic, megakaryocytic)
Serum erythropoetin level below normal reference range
Test Sensitivity
: 70%
Test Specificity
: 90%
No obvious secondary polycythemia cause
Normal arterial
Oxygen Saturation
(>92%)
Complications
Accelerated atherosclerotic and thrombotic disease
Cerebrovascular Accident
Myocardial Infarction
Peripheral Vascular Disease
Other rarely affected vessels
Mesenteric thrombosis
Hepatic vein thrombosis or
Portal Vein Thrombosis
Hemorrhage
and
Bleeding Diathesis
with extreme
Thrombocytosis
>1.5M (acquired
Von Willebrand Syndrome
)
Epistaxis
Acute
GI Bleed
Myeloproliferative Disease Progression (typically after 10 years of PCV)
Myelofibrosis
(20% of patients)
Acute Myeloid Leukemia
(5% of patients)
Management
Myelosuppression
Goal: Keep
Hematocrit
below threshold
White men:
Hematocrit
<45%
Black patients and all women:
Hematocrit
<42%
Low risk (age <60 years old without prior thrombosis)
Low dose
Aspirin
Repeated phlebotomy
High risk (age >60 years old OR prior thrombosis, possibly
Leukocytosis
>10k/mm3)
First-line
Hydroxyurea
Interferon alfa
-2b
Second-line
JAK2 Inhibitor (e.g.
Ruxolitinib
)
Other agents in elderly (>70-80 years old) or advanced disease (leukemogenicity risk)
Busulfan
Pibobraman
Refractory (
Hydroxyurea
refractory, massive
Splenomegaly
, severe symptoms)
JAK2 Inhibitor (e.g.
Ruxolitinib
)
Management
Pruritus
Antihistamine
s
Paroxetine
Oatmeal Bath
Interferon alfa
-2b
Diehn (2001) Br J Haematol 115:619-21 [PubMed]
Prognosis
Median survival in symptomatic patients
Survival without treatment: 6-18 months
Survival with treatment: >10 years
Median survival: 14.1 years
Median survival in age over 60 years with thrombosis history: 8.3 years
References
Tefferi in Schrier (2015) Clinical Manifestations and Diagnosis of Polycythemia Vera, UpToDate, accessed 12/15/2015
Tefferi in Schrier (2015) Prognosis and Treatment of Polycythemia Vera, UpToDate, accessed 12/15/2015
Griesshammer (2015) Ann Hematol 94(6):901-10 +PMID:25832853 [PubMed]
Stuart (2004) Am Fam Physician 69(9):2139-46 [PubMed]
Tefferi (2001) Am J Med 109:146 [PubMed]
Tefferi (2003) Mayo Clin Proc 78:174-94 [PubMed]
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