Why does hypoxia cause polycythemia

Some of the conditions that can cause this are:. In rare cases , the cause of secondary polycythemia can be genetic. This is usually due to mutations that cause your red blood cells to take up abnormal amounts of oxygen.

A recently discovered risk is having a high red cell distribution width RDW , which means that the size of your red blood cells can vary a lot.

This is also known as anisocytosis. Your doctor will want to determine both secondary polycythemia and its underlying cause. Your treatment will depend on the underlying cause. The doctor will take a medical history, ask you about your symptoms, and physically examine you.

One of the secondary polycythemia indications is a hematocrit test. This is part of a complete blood panel. Hematocrit is a measure of the concentration of red blood cells in your blood. If your hematocrit is high and you also have high EPO levels, it could be a sign of secondary polycythemia. Low-dose aspirin works as a blood thinner and can reduce your risk of stroke thrombosis from the overproduction of red blood cells. Your doctor will determine how much blood should be drawn and how often.

The procedure is almost painless and has a low risk. You need to rest after a blood draw and be sure to have a snack and plenty of liquids afterward. In some cases, your doctor will choose not to lower your elevated red blood cell count. Fortunately, it is faster and easier to test for JAK2 mutations when patients have elevated levels of red cells. JP We used to think that sleep apnea was a cause, which makes sense because someone who stops breathing at night would produce more erythropoietin—at least in theory.

The evidence does not support this association, however. Some patients develop polycythemia after kidney transplant, which is known as post-transplant erythrocytosis. Patients may develop increased levels of cobalt and manganese, or tumors that secrete erythropoietin.

Some patients engage in surreptitious doping with erythropoietin. JP Yes, I absolutely do. We have a lot of evidence indicating that ignoring iron deficiency is bad medicine. Hemoglobin requires iron, as do the muscles, the brain, and all other tissues. If someone who has pulmonary hypertension and too many red cells in a high-altitude environment chronic mountain sickness is treated with phlebotomy, we have created iron deficiency and worsened the pulmonary hypertension.

I believe that always using phlebotomy to treat all forms of polycythemia is misguided and can even be harmful. It can improve the laboratory test results, such as the hemoglobin level, which makes us physicians feel better but is bad for the patients. If symptomatic iron deficiency develops in a patient following phlebotomy, we can address that with a short course of oral iron supplementation, and the patient will usually experience an immediate decrease in fatigue and improvement in quality of life.

I generally prefer to normalize the blood cell counts in polycythemia vera with hydroxyurea or another treatment. The 2 other options currently available are pegylated interferon and the JAK2 inhibitor ruxolitinib Jakafi, Incyte.

No proven therapy exists for congenital disorders of hypoxia sensing or high hemoglobin affinity for oxygen. JP This syndrome was first described among people of Asian origin living in a European area of Russia, the Chuvash Autonomous Soviet Socialist Republic; however, it is present worldwide, with another area of endemicity in the Italian island of Ischia.

Chuvash polycythemia is caused by a germline mutation in the VHL gene that is inherited in an autosomal-recessive manner from both parents. This disorder of hypoxia sensing, the first to be described, results from a loss-of-function mutation in a negative regulator of HIFs, the VHL gene. Only intact HIF dimers have function. In the presence of oxygen, the subunits of HIF-a undergo prolyl hydroxylation by prolyl hydroxylase; to function, this enzyme requires the presence of iron and it is inhibited by cobalt and manganese.

Hydroxylation of the proline in the subunits of HIF-a changes the configuration of these proteins, which then bind to the von Hippel-Lindau protein, resulting in their ubiquitination and rapid proteasomal degradation.

Thus, people with Chuvash polycythemia have a congenital defect leading to high HIF levels and thus the production of excessive amounts of erythropoietin. Intriguingly, other VHL mutations cause tumor predisposition syndrome, whereas the Chuvash VHL mutation causes congenital polycythemia, but not tumors. This mutation not only results in a very high level of HIF and increased erythropoietin secondary erythrocytosis but also causes erythroid progenitor hypersensitivity to erythropoietin, a feature of primary polycythemia.

The morbidity and mortality of Chuvash polycythemia result principally from an increased occurrence of thrombosis that is not relieved and is even increased by phlebotomy; however, the cause is not the high hematocrit but too much HIF, which dysregulates genes in the thrombotic pathway protein S, tissue factor, thrombospondin 1, and likely others.

A least 2 other disorders in addition to Chuvash polycythemia are congenital disorders of hypoxia sensing—caused by an HIF-2a encoded by the EPAS1 gene mutation.

The same molecular and pathophysiologic defects associated with the inherited EGLN1 mutation encoding prolyl hydroxylase 2 can also be acquired from cobalt and manganese poisoning, as well as iron deficiency.

These conditions block the activity of prolyl hydroxylase and increase HIFs. Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia. Updated April Your Privacy Rights. To change or withdraw your consent choices for VerywellHealth. At any time, you can update your settings through the "EU Privacy" link at the bottom of any page.

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Kasper, Dennis L.. Fauci, and Stephen L.. Harrison's Principles of Internal Medicine. New York: Mc Graw Hill education, Related Articles. Rheumatoid Arthritis and Anemia. Symptoms of Iron Deficiency Anemia. Other laboratory findings are not very helpful, as even bone marrow aspirates are usually normal. Treatment: to address secondary polycythemia, one should treat the underlying cause. The prognosis depends on the nature of the primary disease.

Primary polycythemia can be treated by intermittent therapeutic phlebotomy to maintain the PCV in the normal range. Because a sudden decrease in blood volume can result in marked hypotension, the blood collection should be accompanied by a concurrent infusion of saline solution.

Thrall M. Wiley-Blackwell, Nelson R. Mosby Elsevier,