Secondary erythrocytosis (secondary polycythemia): causes, symptoms, diagnosis, treatment

Secondary erythrocytosis (secondary polycythemia) is erythrocytosis that develops secondarily due to other factors. Secondary erythrocytosis is a condition in which the level of red blood cells (erythrocytes) in the blood is elevated due to some underlying cause or condition. This differs from primary erythrocytosis, where the elevated red blood cell level is due to a bone marrow disorder.

Frequent causes of secondary erythrocytosis are smoking, chronic arterial hypoxemia and tumor process (tumor-associated erythrocytosis). Less common are hemoglobinopathies with increased affinity of hemoglobin to oxygen and other hereditary disorders.

In smoking patients, reversible erythrocytosis may be the result of tissue hypoxia caused by an increase in the concentration of carboxyhemoglobin in the blood; the level of erythrocytes often normalizes after smoking cessation.

Patients with chronic hypoxemia [due to lung disease, right-to-left intracardiac shunt, prolonged exposure to high altitude, or hypoventilation syndromes] often develop erythrocytosis. The mainstay of treatment is to eliminate the underlying cause; oxygen therapy may help in some cases. Phlebotomy may be used to reduce blood viscosity and relieve symptoms.

High-affinity hemoglobinopathies are rare and occur in certain geographic areas. The diagnosis is usually suspected by taking a family history (erythrocytosis in other relatives) and is confirmed by determining P ₅₀ and, if possible, constructing a complete oxyhemoglobin dissociation curve. Standard hemoglobin electrophoresis is usually within normal limits and does not reliably exclude this cause of erythrocytosis.

Tumor-associated erythrocytosis may be seen in renal tumors and cysts, hepatomas, cerebellar hemangioblastomas, or uterine leiomyomas that secrete EPO. In patients with erythrocytosis, serum EPO levels should be measured and, if serum EPO is normal or elevated, abdominal CT should be performed. Tumor removal may normalize red blood cell levels.

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Causes secondary erythrocytosis

Secondary erythrocytosis can be caused by a variety of factors and conditions, including:

1. Hypoxia: A lack of oxygen in the body's tissues can stimulate the bone marrow to increase red blood cell production. Hypoxia can be associated with chronic lung disease, obstructive sleep apnea, altitude sickness, and other conditions that reduce oxygen supply.
2. Polycythemia: This is a condition characterized by excessive production of red blood cells. Polycythemia can be secondary and caused by a variety of reasons, including hypoxia, hypersecretion of erythropoietin (a hormone that stimulates red blood cell production), or vascular disorders.
3. Chronic diseases: Some chronic diseases, such as chronic kidney disease or chronic lung disease, can cause secondary erythrocytosis due to their effect on the balance of oxygen and erythropoietin.
4. Hypoxic conditions: Secondary erythrocytosis can develop in the presence of hypoxic conditions, such as prolonged exposure to high altitude (mountain sickness), obstructive sleep apnea, and even long-term smoking.
5. Upper airway polycythemia: This is a condition in which the oxygen saturation of the blood is reduced due to problems in the upper airway, such as in obstructive sleep apnea.
6. Medications: Some medications, such as androgens or erythropoietin, can cause secondary erythrocytosis as a side effect.

Pathogenesis

The pathogenesis of secondary erythrocytosis is associated with various factors and mechanisms, depending on the underlying cause. Here are some common pathogenetic points:

1. Hypoxia: One of the main causes of secondary erythrocytosis is hypoxia, which means a lack of oxygen in the body's tissues. Hypoxia can occur due to various conditions such as chronic lung disease, obstructive sleep apnea, altitude sickness, and others. Hypoxia stimulates the kidneys to increase the synthesis and release of erythropoietin (a hormone that stimulates the formation of red blood cells). Erythropoietin acts on the bone marrow, stimulating it to increase the production of red blood cells.
2. Genetic and molecular factors: In rare cases, secondary erythrocytosis may be caused by genetic mutations that affect the regulation of red blood cell production and erythropoietin levels.
3. Chronic diseases: Chronic diseases such as chronic kidney disease can alter iron balance and hormone levels, which can lead to secondary erythrocytosis.
4. Obstructive sleep apnea: This condition is characterized by temporary cessation of breathing during sleep and is often associated with a decrease in oxygen in the blood, which stimulates the production of red blood cells.
5. Medications: Some medications, such as androgens or erythropoietin, can directly act on the bone marrow and increase red blood cell production.
6. Hypersecretion of erythropoietin: Rarely, hypersecretion of erythropoietin may occur due to tumors or other causes, which also contributes to secondary erythrocytosis.

Understanding the pathogenesis of secondary erythrocytosis is important for choosing the best approach to treatment and management of the underlying causes of this condition.

Symptoms secondary erythrocytosis

Symptoms of secondary erythrocytosis may vary depending on the underlying cause and severity of the condition. However, there are common signs that most patients with this condition may experience. Here are some of them:

1. Polycythemic symptoms: Secondary erythrocytosis is often accompanied by an increase in the number of red blood cells in the blood. This can lead to symptoms associated with polycythemia, such as headache, dizziness, weakness, difficulty breathing, and cyanosis (a bluish tint to the skin and mucous membranes due to lack of oxygen).
2. Enlargement of the spleen and liver: In some cases, especially in chronic forms of secondary erythrocytosis, the spleen and liver may increase in size.
3. Symptoms of the underlying condition: Symptoms will depend on the underlying cause of the secondary erythrocytosis. For example, if you have chronic kidney disease, you may have symptoms consistent with kidney failure, such as fatigue, swelling, and changes in your urine.
4. Symptoms of hypoxia: If secondary erythrocytosis is caused by hypoxia (lack of oxygen), symptoms may include difficulty breathing, a feeling of suffocation, rapid heartbeat, and dizziness.
5. Symptoms associated with hypercoagulability: High red blood cell levels can promote the formation of thrombi (blood clots), which can lead to symptoms such as leg pain, swelling, and, in severe cases, thrombosis or embolism.

Symptoms may be involuntary and vary depending on the specific clinical situation.

Diagnostics secondary erythrocytosis

Diagnostics of secondary erythrocytosis includes a number of laboratory and instrumental studies, as well as an assessment of the patient's medical history and physical examination. Here are the main diagnostic methods:

1. Blood test: Laboratory testing of blood samples will help evaluate the level of red blood cells, hemoglobin, hematocrit and other blood parameters. An increase in red blood cell levels above normal values may indicate the presence of erythrocytosis.
2. Erythropoietin level test: Measuring erythropoietin (a hormone that stimulates red blood cell production) levels can help determine whether erythrocytosis is a response to hypoxia.
3. Ultrasound of organs: An ultrasound of the abdomen and pelvis may be performed to look for possible changes in organs such as the liver and spleen that may be related to the underlying cause of secondary erythrocytosis.
4. Medical history and physical examination: The doctor will talk to the patient about his or her medical history, symptoms, and risk factors. A physical examination may reveal signs associated with polycythemia and the underlying cause.
5. Additional tests: Depending on the underlying cause of secondary erythrocytosis, additional tests may be required, such as measuring the oxygen levels in the blood, computed tomography (CT) or magnetic resonance imaging (MRI) of organs, etc.

Treatment secondary erythrocytosis

Treatment of secondary erythrocytosis directly depends on the underlying cause of this condition. The primary goal is to eliminate or control the underlying disease or factor that caused the increased level of red blood cells in the blood. Here are the general approaches to treatment:

1. Treating the underlying cause: If secondary erythrocytosis is caused by chronic conditions, such as chronic kidney disease or chronic lung disease, treatment should be aimed at managing and correcting these conditions. This may include medications, surgery, or other treatments recommended by your doctor.
2. Management of hypoxia: If the elevated red blood cell count is due to hypoxia (lack of oxygen), it is important to eliminate or reduce the source of hypoxia. This may require the use of oxygen therapy, correction of breathing problems, or treatment of the underlying lung disease.
3. Erythropoietin inhibitors: In some cases, especially when there is excess erythropoietin production, erythropoietin inhibitors may be used to control red blood cell levels.
4. Treatment of complications: If secondary erythrocytosis has led to complications such as thrombosis or embolism (blood clots), appropriate treatment, including anticoagulants or antiplatelet drugs, should be given.
5. Regular medical monitoring: Patients with secondary erythrocytosis may need regular medical monitoring and control of red blood cell levels.

Treatment should always be carried out under medical supervision and depends on the specific clinical situation and the underlying cause of secondary erythrocytosis. A thorough examination and specialist consultation are necessary to develop the best treatment plan.

Forecast

The prognosis for secondary erythrocytosis depends on several factors, including the underlying cause of the condition, its severity, and the timeliness of treatment. In most cases, if the underlying disease or factor causing secondary erythrocytosis is successfully treated and controlled, the prognosis is usually good.

However, if secondary erythrocytosis is not detected and treated in time, it can lead to serious complications such as thrombosis (blood clots), embolism, hypertension (high blood pressure), ischemic events (lack of blood supply to organs) and other conditions that can affect the prognosis and quality of life.

It is important to note that successful treatment of the underlying disease or factor causing secondary erythrocytosis can lead to normalization of red blood cell levels and an improved prognosis. Patients with this condition are advised to have regular medical monitoring and follow all doctor's recommendations to control red blood cell levels and prevent complications.