Polycythemia Rubra Vera

Polycythaemia- red cell #
Erythrocytosis – in red cell mass
Absolute Erythrocytosis
- M: Hct >0.60 or >0.52 + RCM >25% of mean
- F: Hct >0.56 or >0.48 + RCM >25% of mean

Apparent Erythrocytosis
- Men: Hct >0.52 + normal RCM
- Women: Hct >0.48 + normal RCM

Relative erythrocytosis
-Normal RCM + Reduced plasma volume (pathological dehydration)

M>F
Median >60yo

2' PRV: treat underlying cause +/- venesection (higher hct threshold)

Classification of Absolute:
EPO dependent
- Appropriate: High altitude, chronic hypoxia, localised hypoxia, congenital
- Inappropriate: Tumors, EPO doping, Testosterone replacement, diabetic meds
EPO independent:
- Acquired: Primary PRV (low EPO level, feedback)
- Congential Polycythemia= mutations in EPO receptors

Inv:
- Tumor Hunt
- Hx + Exam: ?True vs. Apparent
- FBC, U+E, LFTs, Ca2+
- Blood film
- Ferritin: low in 1’ PRV
- EPO
- Imaging
- NB: Normal Hct + High Red Cell # + Low MCV + Low ferritin –> Masked PRV
- Molecular Testing:
JAK2 (V617F)(96-97%)...SAMURAI JACK=BLOODY)
EXXON 12 (3%)
Del (13q), Del (20q), Del (1q), Tris. 8/9
- *SV thrombus 50% chance MPN
- BMBx: Tri-lineage myeloid expansion
- Familial screen for congenital(young)

Sx of primary PRV:
- Arterial*+ Venous clot (splanchnic*)
- Hyperviscosity sx
- Splenic sx
- Gout

Indications for urgent venesection...Hyperviscosity sx

BSH diagnostic:
JAK2 Pos
- Hct M >0.52, F > 0.48. Or RCM >25% above baseline OR Splanchnic vein thrombus
- JAK2 positive
JAK2 Neg= A1-4 + either ≥ 1 A or 2 B’s
A1: Hct M >0.60, F > 0.56. Or RCM >25% above baseline
A2: No JAK2
A3: No 2' cause
A4: BMBx pos
A5: Palpable splenomegaly
A5: Acq. genetics in BM cells
B’s: Plt >450, Neut >10 (>12.5 in smokers), Radiological splenomegaly, Low EPO

Congenital testing

Risk Stratification:
- Thrombi..
ECLAP study
High Risk:>65 + prev clots
Low Risk: <65 + no prev clot
- Malignant Transformation to MF (5-15% in 10 years), AML (2% at 10 year) markers:
Splenomegaly, LDH, HVAF burden >50% at diagnosis

Management:
- Lifestyle...CV factors decrease
- Aspirin +PPI for all (after confirmed)- decrease CV events 60% (ECLAP)
- Venesection first line (?isovolemic)- sx***
CYTO-PV trial: Hct aim <0.45, make iron def.
400-450ml off
Weekly -> 3-4x/year
- If previous clots: Lifelong anticoag (w/out aspirin)
- NB: if plt>1000 (acq. VWF) bleeding risk, 1st cytoreduce

Cytoreduction: (once confirmed primary PRV)
- High risk
- Progressive Hepatosplenomegaly
- Plts >1500
- WCC >15
- Constitutional Sx
- Poor tolerance of venesection

1st line: (OHC then/or IFN)
OHC
- Risk: Macrocytosis, ulcers, SCC, Malignant transformation
NB: pregnancy
Peg IFN-A
Young + fertile
Lowers HVAF
PROUD PV study (2020)
Continuation PV study (2022)
SE: flu like sx, AI disease (*thyroid), mood disturbances

2nd line
Rux: JAK2i (works for EXXON)
RESPONSE + RESPONSE 2 trial
MAJIC PV study
SE: immunosuppression, skin cancer, wean dont stop

Older
Busulfan: 1 dose (w monitoring) vs intermittent
Risk: leuk transformation, pneumonitis**

Pregnancy: inc. DVT
OHC not safe (stop 3 months prior)
IFN 1st
Aspirin
Uterine Doppler from 20wks of gestation?flow
LMWH 6 wks postpartum