Approach to Polycythemia

2021
Case

 25 years old male patient comes with a complaint of

headache, tinnitus & epistaxis of 03 months duration.
 P/E- BP-150/90
 No hepatosplenomegaly
 Lab – Hgb-19 g/dl
 How do you approach the patient & list investigations
Outline
 Definition
 Approach to polycythemia
 Polycythemia rubra vera
 Complication
 Treatment
Definition
 Increased Red Cell Mass (>25% above mean normal
predicted value)
 Usually suspected when abnormally high:
- hematocrit: >0.48 in women and >0.49 in men
- hemoglobin: >16.0 in women and >16.5 in men
(previously >99th percentile of method-specific reference
range for age, sex, altitude of residence)
 Relative vs absolute polycythemia
Approach
Definition

 Is a laboratory finding in which there is increased number

of red blood cells (RBC), along with an accompanying
increase in the concentration of hemoglobin in the
peripheral blood.
 History of pulmonary/cardiac disease, dyspnea, chronic
cough, cyanosis, hyper somnolence
 Smoking history
 Living at high altitude, renal transplantation
 Family history – relatives with history of MPNs,
unexplained erythrocytosis, unexplained thromboses in
unusual sites
 Medications, anabolic steroids, Epo self-inj
 Environmental history – exposure to carbon monoxide
 Thrombotic events, hemorrhage
 Pruritus, erythromelalgia
 symptoms of hyper viscosity (tinnitus, blurred vision,
parasthesias)
Physical Exam

 Pulse oximetry, including with exertion and sleep studies

 Cyanosis, clubbing, plethora of face
 Respiratory and cardiac exam
 Hepatomegaly
 Splenomegaly
Diagnostic Approach
 CBC  Consider based on history:
 Epo level  Carboxyhgb levels
 JAK2 mutation screen  Abdominal ultrasound
 CXR
 Sleep studies
 ECHO:ECG
 Bone marrow studies
Polycythemia Rubra Vera
 PV is a clonal hematopoietic stem cell disorder in which
phenotypically normal red cells, granulocytes, and
platelets accumulate in the absence of a recognizable
physiologic stimulus.
 The most common of the MPN, PV occurs in 2.5 per
100,000 persons, sparing no adult age group and
increasing with age to rates over 10/100,000.
 Familial transmission is infrequent, and women
predominate among sporadic cases
  Nonrandom chromosome abnormalities such as deletion
20q and deletion 13q or trisomy 9 occur in up to 30% of
untreated PV patients, but unlike CML, no consistent
cytogenetic abnormality
 JAK2 mutation positive in 95-97%
 JAK2: cytoplasmic tyrosine kinase that causes cytokine
independent activation of several pathways implicated in
EPO receptor signaling
 RBCs grow in vitro in absence of Epo

JAK2 negative? Consider Exon 12 mutation

Clinical feature
 Usually asymptomatic
 Latent phase…
 Asymptomatic
 Proliferative phase…
 Patients may be hypermetabolic or have symptoms of
hyperviscosity or thromboses
 Spent phase…
 Anemia, leukopenia, hepatosplenomegaly, myelofibrosis
(5-15% in 10 years)
 Secondary AML
 Sx common to all types of polycythemia
 Headache, mental acuity, weakness
 Sx more specific to P vera and myeloproliferative
diseases.
 Erythromelalgia
 Paresthesias
 Pruritus
 Tinnitus or blurred vision
 Hypermetabolic symptoms
 Thromboses
 Hemorrhage
 Facial plethora
 Splenomegaly…
 Found in 70% of patients
 Hepatomegaly…
 Found in 40% of patients
 Distension of retinal veins
Caveat
 Criterion number 2 (BM biopsy) may not be required in
cases with sustained absolute erythrocytosis: hemoglobin
levels >18.5 g/dL in men (hematocrit, 55.5%) or >16.5
g/dL in women (hematocrit, 49.5%) if major criterion 3
and the minor criterion are present.
 However, initial myelofibrosis (present in up to 20% of
patients) can only be detected by performing a BM
biopsy; this finding may predict a more rapid progression
to overt myelofibrosis (post-PV MF).
Natural History of PV
Median survival in treated patients: >13 years

< 40yo: 1.8%/year

> 70yo: 5.1%/year

 Counts
 Treatment

n os is
Prog
Po or
 Treatment

for all patients!

Aspirin 2013 Cochrane Review demonstrated
CV risk reduction trend towards decreased thrombosis &
mortality

Vannucchi. Blood 2014; 124:22:3212

Options
 Low dose ASA (ECLAP study)
 Significant reduction in nonfatal MI, nonfatal stroke, major
venous thrombosis, and death from CV cause
 Phlebotomy
 Myelosuppressive agents
 Hydroxyurea
 Alkylating agents such as busulfan
 32P

 Interferon alpha
 Goal of therapy
CYTO-PV (NEJM 2013)
 Phlebotomy +/- cytoreduction
vs

Aspirin hct < 0.45 for M& < 0.42 for F

Phlebotomy
CV risk reduction

Marchioli. NEJM 2013: 368(1):22-33

Phlebotomy
 Generally, the best initial treatment for PRV
 No increase in progression to AML
 Rapid onset
 No BM suppression
 Remove 500 cc blood 1-2x/wk to target Hct 45% in men
& Hct 42% in women, then maintenance every 3 month
 For high risk patients
•Choices: hydroxyurea, interferon, anagrelide
Side effects: myelosuppresion, GI upset,
skin/nail discoloration

•P32 or Busulfan for elderly pts

Resistant/intolerant to HU? vs

•RESPONSE trial (NEJM 2015) –

– ↓ phlebotomy needs, ↓ spleen, ↓ thrombosis, ↓
symptoms

Aspirin Cyto-
Phlebotomy
CV risk reduction reduction
Vannucchi. NEJM 2015: 372:462
Special Issues
 Bleeding
 Rare complication of PRV usually seen in pts with
thrombocytosis
 Usually due to acquired VWD
 Goals: withdraw meds, correction of thrombocytosis,
consider DDAVP, tranexamic acid
 Thrombosis…
 Start HU and phlebotomy, anticoagulate
 Duration of anticoagulation unclear… ? life-long
 Erythromelalgia
 ASA, attempt to lower platelet count
Management of Pruritus
Finazzi G, et al. Blood 2007; 109: 5104-11

 Options:
 Antihistamines
 Interferon 3mU 3x/wk
 Paroxetine 20 mg/d (SSRI)
 Psoralen plus UVA light
 Avoid heat
Reference
 Blood journal
 Harrison principle of internal medicine,20th edition
Assignment
 Read on ET and primary myelofibrosis
 Thank you!