HomeHealth articleshypoxiaWhy Is There an Increase in Mortality Rate in Patients With Chuvash Polycythemia?

Chuvash Polycythemia- Causes, Symptoms, Diagnosis, Complications and Management

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Oxygen sensing is a principal function. What happens when there is an abnormality in the oxygen sensing and the associated complications? The below article is detailed about the same.

Medically reviewed by

Dr. Mohammad Rajja

Published At August 18, 2022
Reviewed AtAugust 18, 2022

Introduction:

Chuvash polycythemia is a hereditary condition different from polycythemia vera, which was first recognized in the year 1970 by Russian hematologist Lydia Andreevna Polyakova. She found out that this condition is different from polycythemia vera and is an inherited condition. This condition affects around 100 people in the Chuvash Republic of the Russian Federation. Though this condition is endemic to the Chuvash population, this mutation can occur worldwide and originates from an ancient event.

What Is Chuvash Polycythemia?

Chuvash polycythemia is an inherited condition caused by a specific mutation in the VHL (von Hippel-Lindau) gene that results in the substitution of R200W amino acid, leading to increased levels of hypoxia-inducible factor (HIF)-1 and HIF-2 resulting in hypoxic response even when the oxygen levels are normal. This condition results in increased concentrations of erythropoietin, the hormone that regulates the production of red blood cells (RBC), causing polycythemia.

In this Chuvash polycythemia, the patients respond to normal oxygen levels as if they are in a hypoxic environment and produce more red blood cells than required.

How Do I Know If I Have Chuvash Polycythemia?

Chuvash polycythemia can be identified by getting a routine blood test. On examination of the blood tests, there will be elevated hemoglobin and hematocrit levels. Initially, there will be no symptoms, or they may report headaches.

Chuvash polycythemia is also marked by:

  • Vertigo.

  • Dizziness.

  • Leg varices.

  • Increased systolic pulmonary artery pressure.

  • Hemorrhage.

  • Aberrant iron metabolism.

  • Thrombosis that is not correlating with hematocrit elevation.

  • Vertebral and hepatic hemangiomas.

  • Lower white blood count and reduced platelets count.

  • Major bleeding episodes.

How Does Chuvash Polycythemia Develop?

Chuvash polycythemia is an inherited autosomal recessive condition. Several studies showed that the disease was caused by a specific mutation in the VHL (von-Hippel-Lindau) gene resulting in the substitution of R200W amino acid. This condition leads to increased hypoxia-inducible factors (HIF)-1 and HIF-2 and upregulation of the hypoxic response even when the oxygen levels are normal. This results in an increased concentration of erythropoietin, the hormone that regulates red blood cell production.

What Is the Role of Von-Hippel-Lindau (VHL) In Chuvash Polycythemia?

Von-Hippel-Lindau (VHL) is a gene that is involved in the hypoxia sensing pathway. Hypoxia-inducible factor (HIF)-1 and HIF-2 are the transcription factors that help regulate the body’s response to hypoxia. The VHL protein spots the alpha subunits of HIF-1 and HIF-2 for destruction when normal oxygen levels. These alpha subunits are constantly produced, and under normal oxygen levels, they get degraded by the process that is initiated by the VHL protein.

When these cells are exposed to hypoxia, these HIF subunits are no longer degraded by the process that is initiated by the VHL protein. Instead, they survive and combine with a constitutive beta HIF subunit and cause altered regulation of many different genes. Whereas in the case of Chuvash polycythemia, the mutation in the VHL gene causes impaired recognition of the alpha subunits of HIFs, causing impaired degradation of the cells under normoxic conditions.

Typically when there are increased levels of HIFs, it can lead to an upregulation of the body’s hypoxic response even when the oxygen levels are normal.

What Are the Complications of Chuvash Polycythemia?

As the patient enters adulthood, there is a marked increase in mortality. The mortality curve is known to diverge by the age of 25 years. A study found that only around 29 % of patients with Chuvash polycythemia survived by the age of 65 compared to the normal individuals born in the same place.

There is a significant increase in stroke and other thrombotic events in patients with Chuvash polycythemia. There was also an increase in the bleeding events, and some of the strokes were hemorrhagic.

The other complications include pulmonary hypertension and hemangiomas.

How Is Chuvash Polycythemia Diagnosed?

Chuvash polycythemia is diagnosed by a combination of medical history, a physical examination which includes blood pressure and body weight, and laboratory tests of the peripheral blood. Blood samples are collected and stored at -70 degrees Celsius.

How Is Chuvash Polycythemia Treated or Managed?

The ideal management of Chuvash polycythemia is not known. Doctors use phlebotomy similar to how they operate in treating polycythemia vera. Still, there are not many studies to prove how effective phlebotomy is in decreasing complications or mortality. One major issue is that frequent phlebotomy procedures can result in iron deficiency. So it is still not known if phlebotomy is appropriate in treating Chuvash polycythemia.

The other forms of treatment include Aspirin and Busulfan.

Why Is There an Increase in Mortality Rate in Patients With Chuvash Polycythemia?

The common cause of death among patients with Chuvash polycythemia is cerebral vascular events. There was also an increase in death from peripheral thrombosis in patients with Chuvash polycythemia.

What Are All Areas Still Under Research In the Case of Chuvash Polycythemia?

Certain patients with Chuvash polycythemia report pulmonary and metabolic complications. It is still not completely elucidated why patients with Chuvash polycythemia have decreased glucose concentrations and reduced hemoglobin A1c levels, reflecting the average glucose levels.

Conclusion:

The hypoxic response affects the other aspects of the body’s metabolism, immune response, and endocrine pathways. Further research is needed in the case of Chuvash polycythemia and its associated coagulation pathways to help prevent at-risk patients from developing complications. The development of potential therapeutic agents can help assess patients with Chuvash polycythemia.

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Dr. Mohammad Rajja
Dr. Mohammad Rajja

General Practitioner

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