What patient is most at risk for polycythemia?

September 26, 2025 •

4 min read

The median age for polycythemia vera diagnosis is around 60 years old, but risk factors are varied and complex. Knowing what patient is most at risk for polycythemia requires understanding the different types of the condition and the diverse factors that can contribute to its development.

Quick Summary

Patients over 60, those with a history of blood clots, and individuals with a JAK2 gene mutation are at the highest risk for polycythemia vera, a specific type of this blood disorder. Risk also varies for other types of polycythemia, which may be secondary to environmental or other medical conditions.

Key Points

Older Age: Patients over 60 are at significantly higher risk for polycythemia vera (PV), with the median age of diagnosis being 60 years old.
History of Blood Clots: A prior history of thrombotic events, such as deep vein thrombosis (DVT) or stroke, is a major high-risk factor for PV.
JAK2 Gene Mutation: The presence of an acquired JAK2 gene mutation, found in 95% of PV patients, is a primary genetic driver of the disease.
Chronic Hypoxia: Conditions that cause long-term low blood oxygen, like COPD, severe sleep apnea, or living at high altitude, put patients at risk for secondary polycythemia.
Lifestyle and Comorbidities: Modifiable factors like smoking, obesity, and uncontrolled cardiovascular diseases can increase overall risk and worsen prognosis for both types of polycythemia.
High-Risk Stratification: Patients are often categorized as 'high risk' for complications if they are over 60 and/or have a history of thrombosis, guiding treatment strategy.

Understanding the Types of Polycythemia

Polycythemia is a condition marked by an increase in red blood cell count, which thickens the blood and increases the risk of blood clots. It is crucial to distinguish between its two primary forms to understand risk profiles accurately: primary polycythemia and secondary polycythemia. Primary polycythemia, most notably polycythemia vera (PV), is a bone marrow disorder caused by a genetic mutation. In contrast, secondary polycythemia is caused by an underlying condition that triggers the body to produce more red blood cells.

Primary Polycythemia: Polycythemia Vera Risk Factors

Polycythemia vera is a rare, slow-growing blood cancer that develops when a mutation in the JAK2 gene causes bone marrow cells to overproduce blood cells. The risk profile for PV is well-defined and includes several key factors:

Age: The most significant non-modifiable risk factor is age. While PV can occur at any age, the median age at diagnosis is around 60 years. Risk increases progressively with advancing age.
History of Thrombosis: A prior history of thrombotic events, such as deep vein thrombosis (DVT), heart attack, or stroke, places a patient in a higher-risk category for future complications.
Genetic Mutation (JAK2): The vast majority—around 95%—of PV patients have an acquired JAK2 gene mutation, specifically JAK2 V617F. While this mutation is typically acquired and not inherited, it is a primary driver of the disease.
Gender: Men have a slightly higher incidence of PV than women.
Ethnicity: Some studies suggest a higher prevalence in individuals of European descent, particularly those of Eastern European Jewish ancestry.

Secondary Polycythemia: Understanding Underlying Causes

Secondary polycythemia arises from an external factor or an underlying medical condition that stimulates the bone marrow to produce more red blood cells. Unlike PV, it is not a cancer but a response to something else. Patients most at risk are those with conditions causing chronic low blood oxygen levels (hypoxia).

Chronic Obstructive Pulmonary Disease (COPD): This and other chronic lung diseases can lead to low oxygen levels, prompting the body to compensate by increasing red blood cell production.
Sleep Apnea: Patients with obstructive sleep apnea experience repeated pauses in breathing during sleep, causing intermittent hypoxia that can trigger polycythemia.
High Altitude: Long-term residence at high altitudes, where oxygen levels are lower, can lead to chronic erythrocytosis.
Smoking: Carbon monoxide exposure from smoking displaces oxygen in red blood cells, creating a state of relative hypoxia and stimulating red blood cell production.
Obesity: Morbid obesity can contribute to both sleep apnea and cardiovascular risk factors that impact oxygen delivery.
Kidney Disease: Certain kidney conditions, such as cysts, tumors, or renal artery stenosis, can cause inappropriate overproduction of erythropoietin (EPO), the hormone that stimulates red blood cell production.

Comparison of Primary vs. Secondary Polycythemia Risk Factors

To clarify the distinctions, the table below compares the key risk factors for primary (PV) and secondary polycythemia.


Feature	Primary Polycythemia (Polycythemia Vera)	Secondary Polycythemia
Primary Cause	Acquired JAK2 gene mutation	Underlying chronic hypoxia or increased erythropoietin
Genetic Link	Strong link to JAK2 V617F mutation	Generally no genetic mutation link (except in rare familial cases)
Age	Median age of diagnosis is ~60; risk increases with age	Can occur at any age, depending on the underlying cause
Environmental Factors	Limited environmental links; some potential links to radiation	Strong links to smoking, high altitude, and carbon monoxide
Cardiovascular Risk	History of thrombosis is a major risk factor for complications	Cardiovascular disease can contribute to hypoxia and worsen condition
Other Conditions	Associated with an enlarged spleen and other hematologic changes	Associated with conditions like COPD, sleep apnea, or kidney disease

Other Contributing Factors and Complications

Regardless of the type, patients with polycythemia often face additional health risks due to thickened blood (hyperviscosity), which can impede blood flow. These complications are often more severe in patients with high-risk features like older age or a history of thrombosis, and can include:

Cardiovascular Risk Factors: Coexisting conditions like hypertension, diabetes, and high cholesterol significantly increase the risk of serious thrombotic events. Managing these conditions is a critical part of a patient's treatment plan.
Lifestyle Factors: Modifiable risk factors such as smoking, obesity, and a sedentary lifestyle can exacerbate the condition and increase overall cardiovascular risk. Smoking cessation is particularly important as it can directly impact oxygen-carrying capacity.

The Importance of Personalized Risk Assessment

Given the complexity of polycythemia, a personalized risk assessment is essential. A hematologist will evaluate a patient based on age, medical history, specific type of polycythemia, and the presence of any genetic mutations. Risk is typically categorized as high or low, with different management strategies tailored for each group.

High-Risk Patients: Generally defined as age 60 or older and/or having a history of thrombosis. Management typically involves more aggressive treatment, such as cytoreductive therapy, in addition to phlebotomy and aspirin.
Low-Risk Patients: Individuals under 60 with no history of thrombosis may be managed with less intense therapy, often starting with phlebotomy and low-dose aspirin.

For more information on the management of these conditions, the Leukemia and Lymphoma Society offers excellent resources: https://www.lls.org.

Conclusion: Who is most at risk for polycythemia?

Determining who is most at risk for polycythemia depends heavily on whether the condition is primary or secondary. For the primary form, polycythemia vera, the highest risk group includes patients over 60, especially those with a history of blood clots and a JAK2 gene mutation. For secondary polycythemia, the risk lies with individuals suffering from underlying chronic conditions like COPD or sleep apnea, or those exposed to high altitudes or chronic carbon monoxide. Comprehensive risk assessment is vital for effective management and for mitigating the risk of dangerous thrombotic events.

Frequently Asked Questions

Primary polycythemia, such as polycythemia vera, is caused by a bone marrow disorder driven by an acquired genetic mutation. Secondary polycythemia is a reaction to an underlying condition, like chronic hypoxia from lung disease, that increases red blood cell production.

While about 95% of polycythemia vera patients have a JAK2 gene mutation, simply having the mutation does not guarantee the development of the disease. Some people have the mutation at very low levels without developing a full-blown myeloproliferative disorder, though it may slightly increase their risk of venous thrombosis.

Primary polycythemia, or polycythemia vera, is considered a type of rare blood cancer known as a myeloproliferative neoplasm, where the bone marrow overproduces blood cells. Secondary polycythemia, however, is not a cancer but a response to another medical condition.

Yes, chronic exposure to high altitudes, where lower oxygen concentration is present, can cause secondary polycythemia. The body increases red blood cell production as a compensatory mechanism to carry more oxygen.

Smoking increases the risk of secondary polycythemia because carbon monoxide from cigarette smoke binds to hemoglobin, reducing the oxygen-carrying capacity of red blood cells. The body then increases red blood cell production to compensate for the perceived lack of oxygen.

For polycythemia vera, a patient is typically considered 'high-risk' if they are 60 years or older and/or have a history of blood clots. This classification helps determine the appropriate level of treatment.

Most cases of polycythemia vera are not inherited but caused by an acquired genetic mutation. In rare instances, however, a familial form has been identified.