Polycythemia Vera

Polycythemia vera (PV) is a clonal stem cell disorder — one of the classical BCR-ABL1-negative myeloproliferative neoplasms (MPNs), alongside essential thrombocythemia and primary myelofibrosis — characterized by erythrocytosis (an absolute increase in red cell mass), most often accompanied by leukocytosis and thrombocytosis, reflecting trilineage marrow proliferation rather than an isolated red-cell problem.^[1] The disease is driven by constitutive activation of the JAK-STAT signal transduction pathway, and the single most important, high-yield diagnostic fact in this chapter is which mutation causes that activation: the JAK2 V617F mutation, in exon 14 of the JAK2 gene, is present in approximately 95% of PV patients, with a JAK2 exon 12 mutation accounting for most of the remainder (approximately 4%).^[1][2] Essentially every case of true PV is JAK2-mutated in one of these two ways — a wild-type JAK2 V617F result together with a normal or elevated erythropoietin (EPO) level makes PV very unlikely and should redirect the workup toward secondary causes rather than toward more exotic PV testing (see Assessment & Diagnosis).^[1]

PV is uncommon but not rare: estimated incidence is approximately 2.8 per 100,000 in men and 1.3 per 100,000 in women, with a prevalence of roughly 22 cases per 100,000.^[1] Median age at presentation is in the 6th decade of life, and only about one-third of patients are diagnosed younger than age 50 — a genuinely important framing fact, since age 60 is itself one of the two pillars of the risk-stratification framework that drives treatment intensity throughout this chapter (see Choose Initial Treatment).^[1]

PV is a non-curative, lifelong disease. Its 2 central management goals, restated throughout this chapter, are preventing thrombohemorrhagic complications and controlling disease-related symptoms — not eliminating the underlying clone.^[1] Life expectancy is measurably shortened compared with an age- and sex-matched general population (an estimated 28% lower 10-year survival), with median survival of approximately 14 years overall, or 24 years if diagnosed before age 60 — figures worth sharing directly with a newly diagnosed patient, since they are considerably better than the word "neoplasm" tends to suggest, particularly for a younger patient with good risk-factor control.^[1] Approximately 10% of PV patients eventually transform to post-PV myelofibrosis, and the risk of transformation to acute myeloid leukemia is reported at 2.3% at 10 years and 5.5% at 15 years, remaining under 10% even at 20 years — a real but genuinely modest cumulative risk that should be framed accurately rather than overstated (see Red Flags & Refer for the complications that drive most of this chapter's urgency in practice: thrombosis, not transformation).^[1]

The majority of PV is now diagnosed incidentally, from an elevated hemoglobin or hematocrit noticed on routine bloodwork done for an unrelated reason — the classic, florid presentation described below is genuinely less common today than it once was, precisely because most patients are caught earlier.^[1] Splenomegaly is present in roughly 30-40% of patients at diagnosis.^[1]

• Age 60 years or older — one of the two pillars of the standard risk-stratification framework that determines whether cytoreductive therapy is added (see Choose Initial Treatment); also an independent adverse prognostic factor for survival in its own right.^[1]
• A prior history of arterial or venous thrombosis — the second pillar of risk stratification, and, together with age 60 or older, defines a patient as "high-risk" regardless of any other factor.^[1]
• Leukocytosis — a white blood cell count of 15 × 10⁹/L or higher is an independent adverse prognostic factor for survival in validated risk models (see Assessment & Diagnosis), and progressive leukocytosis in the 20-25 × 10⁹/L range is itself a reason some clinicians consider cytoreductive therapy even in an otherwise lower-risk patient.^[1]
• Extreme thrombocytosis (platelet count 1,500 × 10⁹/L or higher), particularly if associated with bleeding or acquired von Willebrand disease — a reason to consider cytoreductive therapy on an individualized basis regardless of the standard age/thrombosis risk category.^[1]
• Higher JAK2 V617F allele burden — while allele burden is not itself directly associated with overall survival or leukemic transformation, an increasing allele burden has been specifically associated with fibrotic transformation to post-PV myelofibrosis.^[1]
• Longer disease duration — disease duration beyond 10 years is associated with a higher risk of evolution to post-PV myelofibrosis.^[1]
• Abnormal karyotype — found in roughly 11% of PV patients (trisomy 8, trisomy 9, 13q-, and 20q- among the more common findings), more frequent in patients over 60 and with disease progression; an independent adverse prognostic factor for both survival and leukemic transformation, though its practical prognostic use in routine practice remains under investigation and cytogenetic studies are not routinely performed in PV in Canada.^[1]
• Conventional cardiovascular risk factors — diabetes, hypertension, dyslipidemia, obesity, and smoking all compound the already-elevated thrombosis risk in PV and should be managed aggressively as a core part of treatment, not treated as a separate problem (see Choose Initial Treatment).^[1]

Complications

Post-PV myelofibrosis develops in roughly 10% of patients and is defined by International Working Group criteria: a prior WHO diagnosis of PV plus bone marrow fibrosis of grade 2 or 3 (both required), together with at least 2 of the following 4 additional criteria — anemia (hemoglobin under 135 g/L in men or under 120 g/L in women), a leukoerythroblastic peripheral blood picture, increasing splenomegaly, or 1 or more constitutional symptoms (10% or greater weight loss over 6 months, drenching night sweats, or unexplained fever above 37.5°C).^[1] Leukemic transformation is less common (2.3% at 10 years, 5.5% at 15 years, under 10% at 20 years) but carries a poor prognosis once it occurs; older age, abnormal karyotype, and a leukocyte count of 15 × 10⁹/L or higher are independent risk factors.^[1]

Step 1 — when to suspect PV

PV should be considered whenever there is persistent elevation of hemoglobin (over 165 g/L in men, over 160 g/L in women) or hematocrit (over 49% in men, over 48% in women).^[1] A single elevated value should be repeated before proceeding, since transient or spurious elevation is common.

Step 2 — JAK2 testing and erythropoietin level

JAK2 V617F mutation testing and a serum erythropoietin (EPO) level should be performed together whenever PV is suspected — these 2 tests, interpreted together, do almost all of the diagnostic work. EPO is a genuinely reliable discriminating test: more than 85% of PV patients have a low serum EPO concentration, and an EPO level above the normal range is unusual for PV, with a specificity around 98% for an alternative, secondary cause of erythrocytosis instead.^[1] To get an accurate EPO level, it should be drawn before any phlebotomy is started — phlebotomy itself alters the result.^[1]

• JAK2 V617F positive, EPO low: PV is confirmed on this basis alone (per prior WHO 2008 criteria, still an accepted diagnostic shortcut when the hemoglobin/hematocrit criterion is also met).^[1]
• JAK2 V617F positive, EPO normal or elevated: perform a bone marrow aspirate and biopsy to confirm the diagnosis and help distinguish PV from another myeloproliferative neoplasm.^[1]
• JAK2 V617F negative, EPO low: proceed to bone marrow aspirate/biopsy and test specifically for a JAK2 exon 12 mutation (via next-generation sequencing) before concluding PV is unlikely — this captures the roughly 4% of PV that is exon-12-driven rather than V617F-driven.^[1]
• JAK2 V617F negative, EPO normal or elevated: PV is very unlikely — proceed directly to a secondary-erythrocytosis workup instead (see Differential Diagnosis, below).^[1]

Bone marrow evaluation in a JAK2 V617F-positive patient with erythrocytosis has traditionally added limited diagnostic value and is not routinely required for every patient — it becomes genuinely useful when the diagnosis is otherwise unclear, and cytogenetic studies specifically are not routinely performed in PV in Canada.^[1] When bone marrow is examined, the classic finding is hypercellularity with trilineage proliferation (panmyelosis): pleomorphic megakaryocytes of varying size without significant maturation abnormality, and minimal (grade 1-2) reticulin fibrosis.^[1]

The "masked PV" concept

A small but clinically important subgroup of JAK2 V617F-positive patients presents with hemoglobin/hematocrit values below the older WHO 2008 threshold, despite bone marrow findings genuinely characteristic of PV — termed "masked PV" (mPV). This group may carry an increased risk of thrombosis, thought to reflect late diagnosis and correspondingly inadequate disease control — a real argument for the lower 2016 WHO hemoglobin/hematocrit thresholds used today rather than clinging to the higher 2008 figures.^[1]

WHO diagnostic criteria

^[1][2]

Differential diagnosis — secondary and relative erythrocytosis

Distinguishing true PV from other causes of an elevated hemoglobin/hematocrit is a genuinely important and common diagnostic task, since the management is completely different.

Basic investigations recommended for the initial workup: pulse oximetry and/or arterial oxygen saturation, complete blood count with differential, liver and renal studies, and chest x-ray; where a hypoxia-driven cause is suspected, add arterial blood gas (including carboxyhemoglobin and methemoglobin levels), pulmonary function tests, echocardiography, and overnight oximetry with or without polysomnography as indicated; where a non-hypoxia-driven cause is suspected, add abdominal imaging (ultrasound or CT). If EPO is normal or elevated with no secondary cause identified, an oxyhemoglobin dissociation curve (P50) helps distinguish a high-affinity hemoglobinopathy (low P50) from familial 2,3-bisphosphoglycerate deficiency, with VHL/PHD2/HIF2-alpha mutational testing considered from there.^[1]

Risk stratification and prognostic models

Two validated frameworks are used in PV, serving different purposes: the ELN thrombosis-risk score — the framework this chapter's treatment decisions are actually built around (see Choose Initial Treatment) — classifies a patient as low-risk (0 of: age 60 years or older, or a prior history of arterial or venous thrombosis) or high-risk (1 or more of those factors present).^[1][5] A separate IPSS overall-survival model is used more for prognostic counselling than for treatment selection: adverse points are assigned for age 67 or older (5 points), age 55-66 (2 points), a leukocyte count of 15 × 10⁹/L or higher (1 point), and a prior venous thrombosis (1 point) — yielding low-risk (0 points, median survival approximately 28 years), intermediate-risk (1-2 points, approximately 19 years), and high-risk (3 or more points, approximately 11 years) groups.^[1]

• Maintain hematocrit below 45% in every patient, regardless of risk category — this is the single, evidence-based numeric target this entire chapter's phlebotomy and cytoreductive-therapy discussion is built around (see Choose Initial Treatment for the trial evidence behind this specific number).^[1][6]
• Prevent thrombohemorrhagic complications — the primary reason PV is treated at all, since the disease itself is non-curative and current therapy does not aim to eliminate the underlying clone.^[1]
• Control disease-related symptom burden, with aquagenic pruritus as a specific, high-priority target given how common and disruptive it is (see Pharmacologic Treatment Options); the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS, also called MPN10) is a validated 10-item tool — fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fever — for objectively tracking this over time rather than relying on an unstructured impression of "doing fine."^[1]
• Aggressively manage conventional cardiovascular risk factors — diabetes, hypertension, dyslipidemia, obesity, and smoking cessation — applying the same general-population cardiovascular risk-assessment tools used in current Canadian Cardiovascular Society guidelines, since these compound the already-elevated thrombosis risk intrinsic to PV.^[1]
• Individualize treatment intensity to the patient's ELN thrombosis-risk category (age and thrombosis history) rather than applying one fixed protocol to every patient (see Choose Initial Treatment).^[1]
• Monitor for, and respond promptly to, transformation to post-PV myelofibrosis or acute leukemia — uncommon but consequential events that change the entire management plan (see Red Flags & Refer and Monitoring & Follow-Up).^[1]

Therapeutic phlebotomy

Phlebotomy is well tolerated and serves 2 roles: emergency therapy for a patient with hyperviscosity symptoms, and the backbone of long-term maintenance treatment.^[1] Typical induction: remove approximately 500 mL of blood every other day until a hematocrit under 45% is achieved; a lower volume (approximately 250 mL) should be considered in elderly patients or those with significant cardiovascular comorbidity who may tolerate rapid volume shifts less well.^[1] Once the target hematocrit is reached, recheck a CBC every 4-8 weeks, and arrange maintenance phlebotomy accordingly — typically every 2-3 months — to keep the hematocrit under 45%.^[1] Frequent phlebotomy predictably drives iron deficiency, which over time can itself produce reactive thrombocytosis and microcytosis, and clinically can worsen fatigue and cause restless legs — but iron supplementation is generally avoided in PV, since replacing iron would simply fuel further erythropoiesis and work directly against the treatment goal.^[1]

Low-dose aspirin

Recommended in all patients without a contraindication the randomized, placebo-controlled ECLAP study (n=518) demonstrated a significant risk reduction (RR 0.40) in a combined endpoint of cardiovascular events and venous thrombotic events (nonfatal MI, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes) with low-dose aspirin (100 mg daily) versus placebo, with no significant increase in major bleeding.^[7] Low-dose aspirin is also specifically effective at relieving the vasomotor microvascular symptoms of erythromelalgia, which result from platelet-rich arteriolar microthrombi — a genuinely useful clinical confirmation when a patient's burning-foot pain responds to starting aspirin.^[1] Typical dosing is 81-100 mg once daily.^[1]

Cardiovascular risk-factor management

There are no PV-specific lipid or blood-pressure targets — apply the same general-population cardiovascular risk-assessment tools and targets as current Canadian Cardiovascular Society guidelines, discourage smoking, and treat diabetes and dyslipidemia to standard targets. This matters more, not less, in PV, given the already-elevated baseline thrombosis risk.^[1]

First-line cytoreductive therapy — hydroxyurea or interferon-alfa

The ELN recommends either hydroxyurea or interferon-alfa as first-line cytoreductive therapy — the 2 are not ranked against each other; the choice is individualized.^[1][5]

Second-line — hydroxyurea resistance or intolerance

Hydroxyurea resistance/intolerance is not common but is clinically important when it occurs — estimated at 11.5% of patients at a median of 5.8 years from diagnosis — and is associated with a 5.6-fold increased risk of death, which is exactly why it needs to be recognized and acted on promptly rather than simply pushing the hydroxyurea dose higher indefinitely.^[1] A standardized ELN definition of hydroxyurea resistance/intolerance exists (any 1 criterion is sufficient):

^[1]

Cardiovascular and general lifestyle counselling

• Smoking cessation — actively discouraged in every patient, given the compounding effect of smoking on an already-elevated thrombosis risk.^[1]
• Regular physical activity, weight management, and standard dietary counselling for cardiovascular risk reduction, applying the same general-population targets used in current Canadian Cardiovascular Society guidance rather than a PV-specific target.^[1]
• Adequate hydration and avoiding prolonged immobility (long flights or car travel, prolonged bed rest) where practical, given the baseline thrombosis risk — a genuinely practical point to raise before a patient's next long trip.

Aquagenic pruritus — non-pharmacologic measures

• Avoid hot baths and showers — using lukewarm or cool water instead is the single most direct, low-risk intervention, given the classic aquagenic trigger pattern.^[1]
• Pat the skin dry after bathing rather than rubbing, and apply a plain, fragrance-free moisturizer afterward.
• Identify and avoid other individual triggers where present (sudden temperature change, alcohol, exertion) — these vary between patients and are worth asking about directly rather than assuming water exposure is the only trigger.
• Narrowband UVB phototherapy is an established non-pharmacologic option for pruritus that remains troublesome despite the measures above and initial pharmacologic therapy — a reasonable dermatology referral for a patient with persistent, quality-of-life-limiting itch (see Treatment Failure & Next Step).

Patient education

PV is a lifelong, non-curative but generally well-controlled condition with a considerably better prognosis than the word "neoplasm" tends to suggest, particularly for a younger patient with well-managed risk factors — this reassurance is worth giving explicitly at diagnosis (see Clinical Snapshot).^[1] Teach every patient the specific emergency-level red flags in this chapter, particularly the association between PV and unusual-site (splanchnic) venous thrombosis, since abdominal pain or new ascites should prompt urgent assessment rather than being dismissed as unrelated to a hematologic diagnosis.^[3] Reinforce that maintenance phlebotomy and any cytoreductive therapy are working even when the patient feels well, and that stopping either without medical guidance allows both hematocrit and thrombosis risk to rise again. For a patient on interferon-alfa, teach the mood-change/depression warning signs specifically, given the drug's contraindication in significant mental health disorders (see Choose Initial Treatment and Monitoring & Follow-Up).^[1] For a patient with troublesome pruritus, explicitly validate it as a genuine, common, and treatable PV symptom rather than something to simply endure — many patients are relieved to learn it has a name (aquagenic pruritus) and a structured treatment pathway.^[4]

Pregnancy

Only about 10% of PV patients are diagnosed before age 40, so pregnancy in a patient with established PV is uncommon but genuinely high-stakes: fewer than 60% of pregnancies in PV patients are successful, with first-trimester miscarriage the most common complication, alongside preeclampsia, postpartum hemorrhage, and thrombosis.^[1] Phlebotomy should be used to keep hematocrit under 45% throughout pregnancy, though the normal physiologic hemodilution of pregnancy often reduces hematocrit somewhat on its own.^[1] Hydroxyurea is contraindicated in pregnancy — female patients of reproductive potential need effective contraception while on it, and it should be discontinued before conception is attempted.^[1] Interferon alfa-2b is the recommended cytoreductive agent during pregnancy when cytoreduction is genuinely needed, since the other cytoreductive options carry teratogenic risk; indications for cytoreduction specifically during pregnancy include a platelet count over 1,500 × 10⁹/L or bleeding-related complications.^[1] There is some evidence that low-dose aspirin throughout pregnancy improves the live-birth rate.^[1] Risk-stratified management (adapted from ELN guidance):

^[1]

Perioperative management

Surgery in a patient with PV carries a genuinely elevated risk of both perioperative bleeding and postoperative thromboembolism — a multicenter retrospective study of PV and ET patients found vascular occlusions in 7.7% and major hemorrhage in 7.3% of surgical episodes.^[1] Where feasible, delay elective surgery until blood counts are controlled through cytoreduction and/or phlebotomy, with hematocrit under 45% and counts otherwise normalized ideally for at least 3 months before surgery.^[1] Hold aspirin 5-7 days before surgery to reduce bleeding risk, and give LMWH postoperatively for deep vein thrombosis prophylaxis; mechanical compression stockings are a reasonable option where a bleeding risk precludes pharmacologic anticoagulation.^[1] Ruxolitinib has a real risk of a rebound/withdrawal flare on abrupt discontinuation, so it should generally be continued through surgery where feasible; if it genuinely must be stopped, taper it, discontinuing 1-2 weeks before surgery rather than stopping abruptly on the day of admission.^[1] When a perioperative thromboembolic event does occur, manage it per standard treatment guidelines, and consider indefinite anticoagulation given the high risk of recurrence in an MPN-associated thrombotic event.^[1]

Older adults

Age 60 or older is itself one of the two pillars that defines high-risk PV, so most older patients will already be on cytoreductive therapy by definition.^[1] Consider a lower initial phlebotomy volume (approximately 250 mL rather than 500 mL) in a patient with significant cardiovascular comorbidity who may tolerate rapid volume shifts less well, and consider busulfan specifically in select older patients unable to tolerate hydroxyurea, interferon, or ruxolitinib (see Choose Initial Treatment).^[1]

Renal and hepatic impairment

Dose-adjust hydroxyurea and ruxolitinib per the current product monograph in renal or hepatic impairment, and monitor CBC more closely in this population given a reduced margin for myelosuppression.

Post-PV myelofibrosis and leukemic transformation

These represent a distinct, more aggressive disease phase requiring its own dedicated hematology-directed management rather than an intensification of routine PV therapy — refer promptly (see Red Flags & Refer). Post-PV acute myeloid leukemia in particular is an aggressive disease with very poor outcomes on standard chemotherapy alone; intensive chemotherapy followed by consolidation with allogeneic stem cell transplant is recommended in young, fit patients, with hypomethylating agents or experimental/clinical-trial therapy considered in others.^[1]

• During phlebotomy induction: hematocrit before each session; once the under-45% target is reached, recheck CBC every 4-8 weeks, then transition to maintenance phlebotomy (typically every 2-3 months) to keep hematocrit under 45% indefinitely.^[1]
• On hydroxyurea: CBC monthly during initial titration, then every 3 months once the patient is in a stable steady state; reassess against the standardized ELN resistance/intolerance criteria (see Choose Initial Treatment) at any sign of an inadequate response rather than only informally.^[1]
• On interferon-alfa (conventional or pegylated): CBC to guide dose titration; specifically screen for mood changes/depression at follow-up visits, given the drug's contraindication in significant mental health disorders, along with monitoring for autoimmune or thyroid symptoms and cardiac/ocular complaints.^[1]
• On ruxolitinib: CBC periodically per current product-specific guidance, watching in particular for anemia and thrombocytopenia; ask specifically about herpes zoster symptoms (rash, dermatomal pain) given the elevated reactivation risk observed in the pivotal trial.^[9]
• Symptom burden: reassess periodically with the MPN-SAF TSS/MPN10 tool to track pruritus and overall symptom burden objectively rather than relying on an unstructured impression.^[1]
• Watch for transformation: at routine visits, ask about and examine for progressive splenomegaly, new constitutional symptoms, and check for new anemia or a leukoerythroblastic peripheral blood picture (post-PV myelofibrosis), and watch for rapidly worsening cytopenias (possible leukemic transformation) — see Red Flags & Refer.^[1]
• Cardiovascular risk factors: routine blood pressure, lipid, and glucose monitoring per standard Canadian Cardiovascular Society targets, alongside ongoing smoking-cessation support.^[1]
• Iron status: periodic awareness of phlebotomy-induced iron deficiency, without routinely supplementing iron given its direct conflict with the treatment goal (see Choose Initial Treatment).^[1]

1. Hematocrit not controlled on phlebotomy alone in a high-risk (age 60 or older, or prior thrombosis) patient: this patient should already be on cytoreductive therapy per the risk-stratification framework — add or optimize cytoreductive therapy rather than continuing to escalate phlebotomy frequency indefinitely.^[1]
2. Confirmed hydroxyurea resistance or intolerance (per the standardized ELN criteria in Choose Initial Treatment): switch to ruxolitinib as the standard, Health Canada-approved second-line option; consider interferon-alfa if not already tried, particularly in a younger patient, or busulfan in a select older patient.^[1]
3. Refractory aquagenic pruritus despite adequate cytoreduction and basic non-pharmacologic measures: trial an antihistamine first (cetirizine or hydroxyzine), then escalate to an SSRI (paroxetine 20 mg/day) if inadequate, and refer for narrowband UVB phototherapy for genuinely persistent, quality-of-life-limiting itch; if the patient is otherwise a reasonable candidate for cytoreductive escalation, ruxolitinib has also been reported to improve refractory pruritus in this setting.^[4][1]
4. Recurrent erythromelalgia or other microvascular symptoms despite once-daily low-dose aspirin and otherwise-controlled hematocrit/platelet count: raise a twice-daily split-dose aspirin regimen with the prescriber, given the specific aspirin-resistance pharmacodynamics documented in myeloproliferative neoplasms (see Choose Initial Treatment).^[8]
5. A new thrombotic event while on treatment: reassess adherence and actual hematocrit/platelet control first, treat the acute event per standard thromboembolism management guidelines, consider intensifying cytoreductive therapy, and consider indefinite anticoagulation given the elevated recurrence risk of an MPN-associated thrombotic event.^[1]
6. Rising JAK2 allele burden, progressive splenomegaly, new anemia, or a new leukoerythroblastic peripheral blood picture: evaluate for transformation to post-PV myelofibrosis using the International Working Group criteria (see Red Flags & Refer) and refer hematology rather than simply intensifying routine PV therapy.^[1]
7. Extreme thrombocytosis or unexpected bleeding at a very high platelet count: consider acquired von Willebrand syndrome — obtain von Willebrand studies before starting or continuing antiplatelet/anticoagulant therapy in this specific setting, and escalate cytoreduction.^[1]

• Diagnosing PV from an isolated elevated hemoglobin/hematocrit without checking JAK2 V617F and an erythropoietin level, or without considering secondary and relative causes of erythrocytosis first.^[1]
• Concluding PV is excluded after a negative JAK2 V617F result without considering JAK2 exon 12 testing, particularly when the EPO level is low.^[1]
• Drawing the erythropoietin level after phlebotomy has already started, which distorts the result and undermines its diagnostic value.^[1]
• Starting iron supplementation for phlebotomy-induced iron deficiency without recognizing that this is generally avoided in PV, since it directly works against the treatment goal.^[1]
• Assuming a lower-risk patient needs a less strict hematocrit target — the under-45% target applies to every patient regardless of risk category; risk category determines whether cytoreductive therapy is added, not what the phlebotomy target is.^[1][6]
• Starting or continuing hydroxyurea in a patient who is pregnant or actively planning pregnancy without ensuring effective contraception or timely discontinuation beforehand.^[1]
• Withholding low-dose aspirin from a PV patient without a genuine, specific contraindication.^[1][7]
• Not testing for JAK2 V617F in a patient presenting with unexplained Budd-Chiari syndrome or another splanchnic vein thrombosis — missing an occult PV or other MPN diagnosis that the thrombotic event itself is revealing.^[3]
• Trying multiple antihistamines in sequence for aquagenic pruritus that has already failed an initial antihistamine trial, rather than escalating to an SSRI or another targeted option — the mechanism in PV pruritus is not purely histamine-mediated.^[4]
• Stopping ruxolitinib abruptly (for surgery or any other reason) without a taper, risking a withdrawal symptom flare.^[1]
• Not screening a patient on interferon-alfa for depression or mood change at follow-up, given the drug's specific contraindication in significant mental health disorders.^[1]
• Continuing to escalate phlebotomy frequency alone in a high-risk patient (age 60 or older, or prior thrombosis) instead of adding cytoreductive therapy as the framework actually calls for.^[1]

How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.

Therapeutic Phlebotomy — Foundation of Treatment for Every Patient

Not a drug — the standard first-line intervention for every PV patient regardless of risk category, and can also be used as emergency therapy for hyperviscosity symptoms.

Antiplatelet Therapy

Recommended in essentially all PV patients without a genuine contraindication, regardless of risk category.

First-Line Cytoreductive Therapy

Added to phlebotomy/ASA for high-risk patients (age 60 or older and/or prior thrombosis), or on an individualized basis regardless of risk for extreme thrombocytosis, progressive leukocytosis, symptomatic splenomegaly, severe symptoms, or phlebotomy intolerance. Hydroxyurea and interferon-alfa are both first-line; neither is ranked above the other.

Second-Line Cytoreductive Therapy

For confirmed hydroxyurea resistance/intolerance per the standardized ELN criteria, associated with a materially increased mortality risk if not recognized and acted on.

Aquagenic Pruritus — Stepwise Pharmacologic Approach

Present in roughly 70% of PV patients; involves mast-cell mediators beyond histamine alone, which is why plain antihistamines are often only partially effective.

Adjunct — Hyperuricemia from High Cell Turnover

Not disease-modifying; addresses a specific, real metabolic complication of increased cell turnover, particularly around cytoreductive therapy initiation.