Erythrocytosis Flashcards
Definition of absolute erythrocytosis
Men: Hct >0.6 or >0.52 + RCM >25% mean
Women: Hct > 0.56 or >0.48 + RCM >25% mean
Apparently erythrocytosis definiton
Men: hct > 0.52 + normal RCM
women: hct >0.48 + normal RCM
Relative erythrocytosis definition
Normal RCM and reduced plasma volume (dehydration)
WHO PV Dx criteria
All major criteria or major 1+2 + minor
Major:
1. Male hb >165/hct >0.49. Female hb >160, hct >0.48. Or RCM>25% of baseline
2. BM biopsy features
3. JAK2 V617F or exon 12
Minor
1. Low epo level
BSH PV diagnostic criteria
JAK2 +ve: A1 + A2 (no BMAT required)
JAK2 -ve (very rare): A1-4 + 1 more A/ 2 B criteria
A1: Male hct >0.6, female >0.56 or RCM >25%
A2: no jak2
A3: no secondary cause of erythrocytosis
A4: BM features consistent with PV
A5: palpable splenomegaly
A6: acquired genetic abnormality in BM cells
B: plt >450, neut >10 (12.5 in smokers), us splenomegaly, low epo
BM findings in PV
hypercellular with erythroid hyperplasia + increased mega/myeloid
Wide variation in size of megas
Absent iron stores
Mild to moderate reticulin increase
PV Molecular and cytogenetics other than jak2
-SH2B3 (LNK) mutations
-del 13q, del 20q, del 1q, trisomy 8/9
-TET2 and DNMT3A (but non-diagnostic)
Venesection targets in erythrocytosis
PV: hct <0.45
Apparent erythrocytosis: hct >0.54 or recent thrombosis. Target <0.45
Idiopathic erythrocytosis: if hct >0.54 and increased risk of thrombosis but tailor to risk factors
High affinity hb: symptomatic or asymptomatic with relative with thrombus. Target hct <0.52. Consider EBT before surgery
Hypoxic pulmonary disease: if hct >0.56 or symptomatic. Target 0.5-0.52. Ltot/ace-i to be considered
Cyanotic congenital heart disease: isovolaemic if symptomatic. Management at tertiary cardiac centre
Post renal transplant: Target hct <0.5. Ace-i may reduce
Chuvash polycythaemia (VHL homogenous mutation): consider ruxolitnib. Screen for MEN and pulmonary HTN, hct Target <0.52
Pv risk stratification
High: >65 +/- pv associated thrombus
Low: <65 and no previous history of pv associated thrombus
(High risk if CV risk factors, extreme thrombocytosis, high WCC, poor hct control with venesection)
PV management
- All receive aspirin
- Venesection 1st line
- Cytoreduce if high risk or low risk unable to tolerate venesection, wcc >15, plt >1500, constitutional symptoms, CV risk factors (IHD, diabetes, HTN) or progressive splenomegaly
Drug choices for PV cytoreduction
- HU or IFN dependent on age and ca risk, or heart disease risk
- either hu/IFN whichever not given first
Ruxolitinib 2nd or 3rd line if HU resistent/intolerant
Others: Busulfqn, 32P, pipibroman (leukaemogenic)
RESPONSE trial
222 patients venesection dependent, splenomegaly and HU not tolerated
Confounding factors
Ruxolitinib licensed for PV
RELIEF Trial
Ruxolitnib for symptomatic relief in PV. No better than HU
MAJIC-PV 2023
180 patients chase 2 rux vs best available for HU resistant disease
CR within 1 Yr 43% rux vs BAT 26%
Rux produced Molecular response associated with better outcomes
Jak2 v617f burden associated with thrombus
VAF >75%
