Yes. High hematocrit can be linked to erythropoietin (EPO), a hormone made mainly by the kidneys that tells bone marrow to produce red blood cells. When oxygen levels are low, EPO may rise and increase red blood cell production, raising hematocrit. But high hematocrit does not always mean EPO is high: in some blood disorders, EPO is low, and dehydration can raise hematocrit without extra red blood cell production.
How are hematocrit and erythropoietin connected?
Hematocrit measures the percentage of your blood volume made up of red blood cells. These cells carry oxygen from the lungs to the body's tissues. Erythropoietin, commonly called EPO, is a hormone produced mainly by the kidneys. It signals the bone marrow to make more red blood cells when the body needs them, particularly when oxygen availability is low.
According to MedlinePlus, a high hematocrit can result from an increase in red blood cells or a decrease in the liquid portion of the blood, known as plasma. This distinction matters because EPO is involved in red blood cell production, whereas dehydration can make the hematocrit appear higher by reducing plasma volume without increasing the total number of red blood cells.
Normally, EPO and hematocrit work through a feedback process. As red blood cell levels and oxygen delivery increase, the kidneys generally reduce EPO production. Mayo Clinic Laboratories explains that EPO levels usually vary inversely with hematocrit. However, this relationship is not identical in every condition, so the two test results need to be interpreted together.
Can high erythropoietin cause high hematocrit?
Yes. When EPO levels increase, the hormone can stimulate the bone marrow to produce additional red blood cells. If this leads to an excessive increase in red blood cells, hematocrit may rise. This is one possible explanation for secondary erythrocytosis, a term for an increase in red blood cell production caused by factors outside the primary bone marrow disorder seen in polycythemia vera.
The Merck Manual Professional Edition explains that secondary erythrocytosis can occur when tissues receive insufficient oxygen or when EPO production increases inappropriately. Possible contributing factors include:
- Low oxygen levels: Chronic lung conditions and certain heart conditions can reduce oxygen delivery and stimulate EPO production.
- Living at high altitude: Lower oxygen availability at higher elevations can trigger a normal increase in EPO and red blood cell production.
- Smoking: Tobacco smoke can affect oxygen delivery and may contribute to an increase in red blood cell production.
- Kidney-related conditions: Some kidney problems can alter EPO production. Rarely, certain tumors produce EPO and contribute to elevated red blood cell levels.
Finding one of these factors does not automatically establish the cause of a high hematocrit. The significance depends on the person's health history, oxygen levels, other blood test results, and whether the finding persists over time.
What does low erythropoietin mean when hematocrit is high?
High hematocrit with low EPO can suggest a different process from high hematocrit with elevated EPO. One condition healthcare professionals consider is polycythemia vera, a blood disorder in which the bone marrow produces too many blood cells because of changes in the cells themselves. In this condition, the body may reduce EPO production because red blood cell levels are already elevated.
According to Cleveland Clinic, a lower-than-expected EPO level can be a clue when evaluating possible polycythemia vera, while an elevated level often points toward a secondary cause. Neither result establishes a diagnosis by itself. Clinicians consider the complete blood count, other blood cell measurements, and additional testing when determining the explanation for a persistent elevation.
What if erythropoietin is normal despite high hematocrit?
A normal EPO result does not always settle the question. When hematocrit is elevated, a result that falls within a laboratory's usual EPO reference interval may still need careful interpretation in context. The relationship between EPO and red blood cell production, together with the person's oxygen status and other findings, helps determine whether further investigation is appropriate.
Possible explanations for a high hematocrit include increased red blood cell production and a reduced plasma volume. These mechanisms are different, and an EPO measurement alone cannot reliably distinguish every cause. A healthcare professional may also consider how long the hematocrit has been elevated, whether hemoglobin and red blood cell counts are also high, and whether white blood cell or platelet counts are abnormal.
How do doctors investigate high hematocrit and EPO levels?
The investigation usually begins by reviewing the complete blood count and confirming whether the hematocrit elevation persists. The clinician may ask about smoking, altitude exposure, medical conditions, and medications, as well as any recent illness or fluid loss that could affect plasma volume.
The MedlinePlus erythropoietin test guidance explains that an EPO blood test can help evaluate the cause of abnormal red blood cell levels and certain bone marrow disorders. Depending on the initial findings, further assessment may include:
- A repeat complete blood count: This helps determine whether the elevation persists and provides information about hemoglobin, red blood cells, white blood cells, and platelets.
- An EPO blood test: This measures circulating erythropoietin to help distinguish possible causes of elevated red blood cell levels.
- Oxygen assessment: A clinician may check oxygen saturation or recommend other tests if low oxygen availability is suspected.
- Additional blood testing: Testing for changes in the JAK2 gene may be considered when polycythemia vera is a concern.
- Further kidney or other imaging tests: These may be appropriate when the findings suggest an underlying kidney problem or another source of increased EPO.
The tests selected depend on the initial results and the person's clinical circumstances. EPO reference intervals also vary between laboratories, so a result should be compared with the interval provided by the testing laboratory rather than interpreted using a universal cutoff.
When should high hematocrit be medically reviewed?
A high hematocrit found on a routine blood test should be discussed with a healthcare professional, especially if it remains elevated on repeat testing or occurs alongside other abnormal blood results. The clinician can determine whether fluid loss, oxygen-related factors, a medication, or a blood or kidney disorder needs further evaluation.
The NHS guidance on erythrocytosis notes that this condition can be associated with blood clots. Seek emergency medical care for sudden difficulty breathing, chest pain, coughing up blood, or symptoms suggestive of a stroke. New pain and swelling in one leg also need urgent medical assessment because they may indicate a blood clot.
Do not try to lower hematocrit or change prescribed medication solely on the basis of an EPO result. Management depends on the underlying cause, and treatments appropriate for one type of erythrocytosis may not be appropriate for another.