Fatigue in PV is caused by several factors co-occurring, indicating that it stems from multiple causes working together rather than a single reason.

1. Thickened blood and poor oxygen delivery

In PV, excess red blood cells make the blood thicker (hyperviscosity), which occurs when you have too many red blood cells; as a result, oxygen moves more slowly through your body, slowing circulation and oxygen delivery to tissues. As a result, the body and brain may not get enough oxygen, leading to exhaustion and headaches.

2. Chronic inflammation

PV is associated with ongoing, low-grade inflammation, even when blood counts are controlled. Inflammatory molecules such as cytokines can affect the brain’s energy regulation and cause fatigue similar to that seen in autoimmune diseases [2].

3. Bone marrow overactivity

The bone marrow works harder than normal, using up more of the body’s energy, which can make you feel weak or tired.

4. Psychological and emotional factors

Fatigue is closely linked with depression and anxiety, which are common in people living with myeloproliferative neoplasms (MPNs) like PV [2]. Constant symptom monitoring and uncertainty about the disease course can amplify tiredness.

5. Treatment effects

Some PV medicines—such as cytoreductive therapy—can initially cause you to feel more tired, but this typically improves once your doctor adjusts the dose. Adjusting the dose or timing often improves this without stopping therapy.

Patients often describe fatigue in PV as more than just feeling sleepy. Common experiences include:

• Feeling drained even after sleeping well
• Difficulty concentrating or thinking clearly (“brain fog”)
• Needing frequent naps but waking still tired
• Shortness of breath with light activity
• Low motivation or mood swings

In a study that included more than 2,500 PV patients in the U.S., fatigue was rated as the most burdensome symptom, often more severe than itching or spleen discomfort [1].

Sometimes, worsening fatigue signals that PV is not fully controlled. Studies show that fatigue severity often correlates with higher amounts of red blood cells in your blood or symptom scores, even when routine lab tests look “normal” [3].

If fatigue suddenly worsens, clinicians may check for:

• Rising red blood cell or white cell counts
• Enlarged spleen
• Low iron levels (from repeated phlebotomy)
• Early signs of myelofibrosis (bone marrow scarring)

Managing fatigue requires a combined medical and lifestyle approach.

1. Optimize PV control

• Phlebotomy (blood removal treatment) helps reduce hematocrit levels below 45%.
• Low-dose aspirin prevents clotting and improves circulation.
• Interferon therapy may reduce fatigue by lowering inflammation and stabilizing the disease.

2. Address contributing factors

• Correct anemia or iron deficiency from frequent blood draws.
• Manage depression and sleep problems with counseling or medication.
• Balance activity and rest: Gentle exercise can reduce fatigue over time; even though it may seem tiring, it can actually help.

3. Track and communicate symptoms

Tools such as the MPN-SAF Total Symptom Score (TSS) enable patients to record their fatigue levels, allowing clinicians to adjust treatment accordingly [2]. Your doctor may use a brief symptom checklist to monitor your fatigue.

4. Supportive and non-drug options

• Stay hydrated to maintain blood flow.
• Avoid prolonged periods of sitting to promote healthy circulation.
• Gentle stretching, yoga, or mindfulness practices help alleviate both mental and physical fatigue.

1. Why do I still feel tired even when my PV blood counts are normal?

Fatigue can persist because inflammation and energy imbalance in PV continue even when blood counts are well controlled. It doesn’t always mean your disease is worsening, but it’s worth discussing with your doctor.

2. Can fatigue mean my PV is getting worse?

Possibly, fatigue sometimes worsens when the disease becomes more active or transforms into myelofibrosis. Regular check-ups help rule out progression or anemia-related causes.

3. What treatments help reduce PV fatigue?

Phlebotomy, interferon therapy, and good hydration may help. If fatigue is severe, your clinician might adjust medications or refer you for supportive therapies such as physical rehabilitation or counseling.

4. Is exercise safe when I feel exhausted?

Yes, gentle exercise is beneficial. Activities like walking or yoga improve circulation, reduce inflammation, and boost energy over time. Always start slowly and pace yourself.

5. Can mental health treatment help PV fatigue?

Absolutely, fatigue and depression often overlap. Addressing both together, through therapy, mindfulness, or medication, can significantly improve overall well-being.

1. Grunwald, M. R., et al. (2019). Symptom burden and blood counts in PV patients: REVEAL study. Clin Lymphoma Myeloma Leuk, 19(9), 579–584.
2. Radia, D., & Geyer, H. L. (2015). Management of symptoms in PV and ET patients. Hematology ASH Educ Program, 2015(1), 340–348.
3. Geyer, H., et al. (2016). Symptomatic profiles of PV patients: implications of inadequately controlled disease. J Clin Oncol, 34(2), 151–159. .