Risk Stratification in Polycythemia Vera

Topic 05 · Myeloproliferative Neoplasms

Ashwin Kishtagari, MBBS, MSCI

Division of Hematology/Oncology, Vanderbilt University Medical Center

2026-08-18

Overview

Two questions risk assessment answers

Risk stratification in PV addresses two distinct clinical questions, and it helps to keep them separate.

1. Thrombosis risk — how likely is a clotting event? Drives day-to-day management.

2. Survival & progression risk — long-term prognosis, including transformation to myelofibrosis or acute leukemia. Informs counseling and monitoring.

The most clinically actionable axis is thrombosis risk — it directly determines whether a patient needs cytoreduction. Survival prognostication is more about counseling and follow-up intensity.

Why thrombosis dominates

Thrombosis is the leading cause of morbidity and mortality in PV.

• Both arterial and venous events
• Can be the presenting feature of the disease
• Reducing thrombotic risk is the central goal of PV management

Thrombosis Risk

The conventional two-tier model

Standard thrombosis risk stratification rests on two factors:

• Age ≥ 60 years
• History of prior thrombosis

Risk category	Criteria
Low risk	Age < 60 and no prior thrombosis
High risk	Age ≥ 60 or prior thrombosis

This simple, well-validated two-tier scheme is the backbone of most treatment algorithms. Either risk factor alone is enough to classify as high risk.

Risk modifiers

Beyond the two core factors, several features modulate risk and influence decisions at the margins:

• Cardiovascular risk factors — hypertension, smoking, diabetes, hyperlipidemia

• Leukocytosis — elevated white cell count, increasingly recognized as associated with thrombosis

• JAK2 V617F allele burden — higher burden linked to more thrombotic events in some studies

Note

These modifiers refine the picture but do not replace the core age / prior-thrombosis classification in the conventional model.

From Risk to Treatment

Management by risk tier

Risk maps directly onto a risk-adapted treatment strategy.

	Low risk	High risk
Phlebotomy	✓ (target HCT)	✓ (target HCT)
Low-dose aspirin	✓	✓
CV risk management	✓	✓
Cytoreduction	—	✓

First-line cytoreduction is typically hydroxyurea or pegylated interferon; ruxolitinib is used when patients are resistant to or intolerant of hydroxyurea.

The hematocrit target — evidence

A defining piece of evidence is the CYTO-PV trial.

• Compared a hematocrit target of < 45% vs 45–50%
• The < 45% group had a significantly lower rate of cardiovascular death and major thrombosis

This established HCT < 45% as the standard phlebotomy target for all patients, regardless of risk tier.

Aspirin — evidence

The role of low-dose aspirin is supported by the ECLAP trial.

• Low-dose aspirin reduced thrombotic events
• No significant excess of major bleeding

Hence low-dose aspirin for most patients, unless contraindicated (e.g. bleeding risk, very high platelet counts with acquired von Willebrand syndrome).

Survival & Progression

Prognostic models for survival

Separate from thrombosis risk, survival prognostication uses different factors.

A validated model (IWG-MRT) stratifies overall survival using:

• Age
• Leukocytosis (elevated WBC)
• History of venous thrombosis

This yields low / intermediate / high risk groups for overall survival — distinct from the two-tier thrombosis model.

Molecular prognostication

Mutational data adds prognostic resolution.

• Beyond JAK2, certain additional somatic mutations (e.g. in genes such as SRSF2) are associated with worse survival and higher progression risk
• Useful for counseling and deciding monitoring intensity

Warning

This deck is an educational scaffold built from well-established concepts. Verify all thresholds, criteria, and trial figures against current authoritative guidelines (e.g. NCCN, ELN) before any teaching or clinical use.

Summary

• Risk assessment in PV answers two questions: thrombosis risk and survival risk
• Thrombosis is stratified by age ≥ 60 and prior thrombosis → low vs high
• Modifiers: CV risk factors, leukocytosis, JAK2 allele burden
• Management is risk-adapted: phlebotomy (HCT < 45%) + aspirin for all; cytoreduction added for high risk
• Survival prognostication uses a separate model (age, WBC, venous thrombosis) plus molecular features

Connects back to the overview and ruxolitinib decks: this is the framework that decides who needs cytoreduction, and ruxolitinib is the option once hydroxyurea fails.