What is the likelihood that a patient with borderline elevated hemoglobin for eight years, normal spleen size, normal white‑blood‑cell and platelet counts, no constitutional symptoms, and no JAK2 testing has polycythemia vera of any type?

Likelihood of Polycythemia Vera in This Clinical Scenario

The probability of polycythemia vera in this patient is very low—likely less than 5%—given the eight-year stability of borderline hemoglobin, normal spleen size, normal white blood cell and platelet counts, and absence of constitutional symptoms. 1, 2

Why This Patient's Presentation Argues Against PV

Temporal Pattern Is Atypical

• Borderline elevation stable for eight years without progression strongly argues against PV, as untreated polycythemia vera typically demonstrates progressive increases in hemoglobin/hematocrit over time, not static borderline values. 3, 4
• The natural history of PV involves clonal myeloproliferation that would be expected to manifest more clearly over an eight-year period if truly present. 5

Absence of Key Clinical Features

• Normal spleen size is notable, as splenomegaly occurs in a substantial proportion of PV patients due to extramedullary hematopoiesis and is a traditional (though not highly sensitive) marker of the disease. 3, 6
• Normal white blood cell and platelet counts make PV significantly less likely, as approximately half of PV patients display thrombocytosis or leukocytosis at presentation. 3
• The absence of constitutional symptoms (weight loss, night sweats, fever) further reduces the probability, though these symptoms are not required for diagnosis. 3

The "Masked PV" Consideration

• Masked PV—where iron deficiency suppresses hemoglobin into the normal or borderline range—remains a theoretical possibility, but several features argue against it in this case:
  • Masked PV typically presents with microcytosis (low MCV) due to iron deficiency, which would be evident on routine CBC. 1, 6
  • Masked PV patients often have accompanying thrombocytosis, leukocytosis, or splenomegaly—all absent here. 1, 7
  • The eight-year stability without any progression makes masked PV unlikely, as this entity was recognized precisely because it carries worse outcomes when undiagnosed and untreated. 4

What the Borderline Hemoglobin Likely Represents

Secondary Polycythemia Is More Probable

• Smoker's polycythemia is the most common cause of borderline-elevated hemoglobin in the general population and should be the primary consideration if the patient has any smoking history. 1
• Chronic carbon monoxide exposure from smoking creates a functional hypoxic state that drives compensatory erythropoiesis, producing stable borderline elevations. 1
• Other hypoxia-driven causes (sleep apnea, chronic lung disease) can produce similar stable borderline patterns. 1, 6

Normal Physiologic Variation

• The 2016 WHO criteria lowered diagnostic thresholds for PV, creating substantial overlap with normal reference ranges—in one study of 248,839 patients with presumptively normal CBCs, 6.48% of men and 0.28% of women met the new hemoglobin/hematocrit thresholds. 2
• This overlap means that borderline values in isolation, without other clinical or laboratory features, have very low positive predictive value for PV. 2

The Critical Role of JAK2 Testing

Why JAK2 Testing Would Definitively Answer This Question

• JAK2 V617F mutation is present in >95% of polycythemia vera cases, making it the single most specific test to confirm or exclude the diagnosis. 3, 6
• JAK2 exon 12 mutations account for an additional 2-4% of PV cases that lack the V617F mutation, meaning comprehensive JAK2 testing approaches 97-99% sensitivity. 3, 8
• A negative JAK2 test in this clinical context would reduce the probability of PV to <3%, effectively ruling out the diagnosis. 5

What to Expect If JAK2 Were Tested

• Given the clinical presentation (stable borderline hemoglobin for eight years, normal counts, no splenomegaly, no symptoms), the pre-test probability of a positive JAK2 is extremely low—likely <5%. 1, 2
• If JAK2 were positive despite this atypical presentation, it would represent either:
  • Very early/indolent PV that has not yet manifested typical features over eight years (unusual). 4
  • JAK2-positive secondary polycythemia (rare but described). 5
  • Coincidental JAK2 mutation with clonal hematopoiesis of indeterminate potential (CHIP) rather than overt PV. 5

Practical Clinical Algorithm for This Patient

Immediate Next Steps (Without JAK2 Testing)

1. Obtain detailed smoking history and measure carboxyhemoglobin if any smoking exposure, as this is the most common reversible cause. 1
2. Screen for sleep apnea with clinical history (snoring, daytime somnolence, witnessed apneas) and consider polysomnography if positive. 1, 6
3. Check serum erythropoietin level:
   • Low EPO (<2 U/L) would dramatically increase PV probability and mandate JAK2 testing. 1, 6
   • Normal or elevated EPO would strongly favor secondary polycythemia over PV. 1, 6
4. Review complete blood count with red cell indices to assess for microcytosis (MCV <80 fL), which would suggest iron deficiency potentially masking higher hemoglobin. 1, 6

When to Pursue JAK2 Testing

• JAK2 testing is NOT indicated based on the current presentation alone, given the very low pre-test probability and eight-year stability. 2
• JAK2 testing WOULD be indicated if:
  • Serum EPO returns low or inappropriately normal. 6
  • Hemoglobin increases ≥2 g/dL from baseline. 1, 9
  • Thrombocytosis, leukocytosis, or splenomegaly develops. 1, 6
  • Microcytosis is present with other PV-suggestive features. 1
  • Unusual thrombosis occurs (Budd-Chiari, portal vein, splenic vein). 6, 7
  • Aquagenic pruritus or erythromelalgia develops. 6

Critical Pitfalls to Avoid

Do Not Over-Investigate Stable Borderline Values

• The isolated use of borderline hemoglobin/hematocrit levels as a trigger for extensive PV workup leads to unnecessary testing in the vast majority of cases, given the overlap with normal population distributions. 2
• Eight-year stability without progression is a powerful negative predictor that should temper diagnostic enthusiasm. 4

Do Not Assume Normal Counts Exclude PV Entirely

• While this patient's presentation makes PV very unlikely, masked PV can present with normal or borderline hemoglobin when iron deficiency is present. 1, 7
• The key distinguishing feature is that masked PV patients typically have microcytosis, thrombocytosis, leukocytosis, or splenomegaly—features absent in this case. 1, 7

Do Not Ignore Reversible Secondary Causes

• Failing to identify and address smoking as a cause of borderline polycythemia is the most common missed diagnosis in this clinical scenario. 1
• Smoker's polycythemia resolves with cessation, with risk reduction beginning within one year and return to baseline after five years. 1

Summary Probability Estimate

Based on the totality of evidence, this patient has approximately a 2-5% probability of having polycythemia vera of any type, with the following reasoning:

• The eight-year stability argues strongly against progressive clonal myeloproliferation. 3, 4
• The absence of thrombocytosis, leukocytosis, splenomegaly, and symptoms reduces the likelihood by at least 50% compared to typical PV presentations. 3, 6
• The borderline hemoglobin alone, given the 2016 WHO threshold changes, has very low positive predictive value in the general population. 2
• Secondary polycythemia (particularly smoking-related) or normal physiologic variation are far more probable explanations. 1, 2

If JAK2 testing were performed and returned negative, the probability would drop to <1%. 5 If serum EPO is normal or elevated, the probability is similarly <1%. 1, 6