Reticulocytosis : Causes, Symptoms, Diagnosis & Treatment

• Classification
• Causes Of Reticulocytosis
• Response To Therapy
• Posthemorrhagic Anemia
• Hemolysis
• Diseases Accompanied By General Hypoxia
• Malignant Blood Diseases
• Rare Causes
• Diagnostics
• Correction
• Conservative Therapy
• Surgery
• Forecast

Reticulocytosis is an increase in the concentration of reticulocytes (immature erythrocytes) in the peripheral blood by more than 1% of the number of all erythrocytes. The main cause is various anemia (posthemorrhagic, hemolytic), as well as pathological conditions that cause general hypoxia in the body. The leading place in the clinical picture is occupied by anemic syndrome - pallor of the skin and mucous membranes, dizziness, palpitations. The level of reticulocytes is examined in the general blood test (CBC). To correct reticulocytosis, it is necessary to treat the underlying disease.

Classification

Taking into account the regenerative ability of the bone marrow, the following reticulocytosis is distinguished:

• True. It is characterized by an increase in the number of reticulocytes in the blood and, at the same time, in the bone marrow. The reason for the activation of hematopoiesis is anemia, bleeding, hemolysis, etc.
• False. Reticulocytosis of peripheral blood is noted in the absence of an increased bone marrow content of reticulocytes. With this variety, immature red blood cells are washed out of the bone marrow. The reason is the irritation of hematopoietic germs by metastases of malignant tumors.

There is also physiological reticulocytosis in newborns. Immediately after birth, the processes of hematopoiesis are activated as an adaptive reaction to extrauterine life. In addition, newborn red blood cells contain fetal hemoglobin, which is why they are destroyed very quickly. The level of reticulocytes on the first day of life ranges from 2 to 40%, then decreases sharply on the second day, and by the age of 10-12 reaches the norm for adults.

Causes of reticulocytosis

Response to therapy

The most common non-pathological cause of reticulocytosis is a reaction to the treatment of iron deficiency, folic acid deficiency anemia. Its occurrence 3-5 days after the start of iron and folic acid preparations, vitamin B12 injections indicates a successful response to therapy. An increase in the concentration of reticulocytes in these cases indicates the normalization of hematopoiesis processes. Also, reticulocytosis can develop after successful chemotherapy or radiation therapy of oncohematological diseases (leukemia).

Posthemorrhagic anemia

Bleeding is considered the most common cause of reticulocytosis. With blood loss (both acute and chronic), the level of hemoglobin decreases. In response, the kidneys secrete erythropoietin, the main physiological stimulator of erythropoiesis. Under its influence, the processes of mitosis and maturation begin to activate in the erythroblasts of the bone marrow. With intensive hematopoiesis, part of the immature erythrocytes enters the blood.

In acute external or internal bleeding (trauma, fracture, rupture of internal organs), reticulocytosis occurs on days 4-5, regresses after about 1 week, its degree depends on the amount of blood loss. The cause of minor but persistent long-term reticulocytosis is chronic bleeding, for example from hemorrhoidal veins. According to the persistent increase in the proportion of reticulocytes, one can also suspect hidden bleeding from the gastrointestinal tract (with gastric ulcer and 12 duodenal ulcer, malignant tumor of the colon).

Reticulocytosis - hematological syndrome

Hemolysis

Another cause of reticulocytosis is recognized as diseases accompanied by the destruction of red blood cells (hemolysis). The scheme of the pathogenesis of reticulocytosis in these pathologies does not differ significantly from that in posthemorrhagic anemia (decreased hemoglobin, erythropoietin). With massive hemolysis, the rate can reach 60-70%. The following diseases are distinguished, accompanied by hemolysis (hemolytic anemia):

• Acquired. The most common variety. These include autoimmune and drug-induced hemolytic anemia associated with the formation of autoantibodies; anemia caused by a defect in erythrocyte membranes (paroxysmal nocturnal hemoglobinuria); thrombotic microangiopathies (Moshkowitz's disease, hemolytic-uremic syndrome).
• Congenital. The reason for the increase in the number of reticulocytes may be hemolytic anemia caused by a violation of the structure of membranes (hereditary microspherocytic anemia), enzyme deficiency (insufficiency of glucose-6-phosphate dehydrogenase) or a defect in the structure of hemoglobin (sickle cell anemia, thalassemia).

Diseases accompanied by general hypoxia

Diseases characterized by a decrease in the partial oxygen content in the blood or a deterioration in general circulation and causing circulatory hypoxia can also cause reticulocytosis. The mechanism of its development is similar to previous pathologies. However, since the level of hemoglobin and erythrocytes does not decrease in diseases of this group, increased hematopoiesis leads not only to reticulocytosis, but also to secondary erythrocytosis and hyperhemoglobinemia. The concentration of reticulocytes reflects the severity of the underlying disease, but does not reach such high numbers as with blood loss or hemolytic anemia.

• Diseases of the lungs. The reason for the increase in the content of immature red cells is usually broncho-obstructive pathologies (COPD, bronchial asthma). Reticulocytosis also occurs in severe restrictive lesions of the lung tissue (histiocytosis X, diffuse alveolitis, idiopathic pulmonary fibrosis).
• Heart diseases. Reticulocytosis is characteristic of the so-called "blue" (cyanotic) congenital heart defects, i.e. malformations, accompanied by a predominant right-to-left blood shunt and depletion of the pulmonary circulation (Fallot's tetrad, transposition of the great vessels, tricuspid valve atresia).

Malignant blood diseases

In some cases, oncohematological pathologies become the cause of reticulocytosis, namely, polycythemia vera (Wakez's disease) and erythroblastic leukemia. The pathological mechanism is due to malignant (clonal, tumor) degeneration of a pluripotent (in polycythemia) or erythroblast (in leukemia) stem cell. Reticulocytosis is persistent, high (can reach up to 30-50%), Polycythemia is also characterized by an increase in the number of all formed elements (leukocytes, erythrocytes, platelets). With erythroblastic leukemia, a large number of blast cells are present in the blood.

Rare Causes

• Climbing to great heights or living in highlands.
• Metastases of cancer cells in the bone marrow: breast cancer, kidney cancer, neuroblastoma.
• Violation of the synthesis of porphyrins : sideroblastic anemia, lead intoxication, porphyria.
• Protozoal infections : malaria.
• Renal ischemia : hydronephrosis, polycystic kidney disease, congenital or atherosclerotic stenosis of the renal artery.
• Taking medications : nitrofurans, non-steroidal anti-inflammatory drugs, glucocorticosteroids.

Diagnostics

The count of reticulocytes is carried out in a clinical blood test. The appearance of reticulocytosis requires an appointment with a doctor for examination in order to find out the cause. First of all, chronic blood loss should be excluded. To do this, the specialist examines the skin and mucous membranes for pallor, measures blood pressure and heart rate. Then an additional examination is assigned, including:

• Laboratory tests. The concentration of hemoglobin, other formed elements (erythrocytes, platelets, leukocytes), a color indicator is measured. A smear is being studied to detect pathological forms of erythrocytes (sickle-shaped, spherocytic, schizocytes). With hemolytic anemia, signs of hemolysis are noted - an increase in the level of indirect bilirubin and lactate dehydrogenase, a decrease in haptoglobin. The content of iron, ferritin is checked. The stool is analyzed for occult blood.
• Specific diagnosis of hemolytic anemia. To determine the nosological form of hemolytic anemia, various tests are performed. Immunological reactions (antiglobulin Coombs test), electrophoresis of hemoglobin and membrane proteins, flow cytometry, tests for osmotic resistance of erythrocytes are performed.
• Instrumental research. To search for the source of bleeding, sigmoidoscopy, esophagogastroduodenoscopy, and colonoscopy are prescribed. If a hemorrhage in the abdominal cavity is suspected, ultrasound or computed tomography is performed. To diagnose diseases of the lungs and heart, chest x-ray, spirometry, echocardiography are performed.
• Histological studies. To confirm malignant blood diseases, it is necessary to study the morphological picture of the bone marrow. With polycythemia, a pronounced hyperplasia of all hematopoietic sprouts (erythroid, granulocytic, megakaryocytic) is noted in the biopsy. Erythroblastic leukemia is characterized by the predominance of atypical erythroblasts (up to 90%) over other cells.

Complete blood count - a method for detecting reticulocytosis

Correction

Conservative therapy

There are no methods to directly reduce the number of reticulocytes. To correct reticulocytosis, it is necessary to eliminate its cause, which implies the treatment of the underlying pathology. Reticulocytosis that occurs a few days after the start of vitamin B12 or iron supplementation is normal and does not require intervention. In the case of a pathological increase in the indicator, depending on the cause, the following treatment is prescribed:

• Blood transfusions. With extensive bleeding or massive hemolysis, leading to severe anemia (hemoglobin below 5 g / l), transfusions of whole blood or its components (erythrocyte mass, washed erythrocytes, thrombotic concentrate) are required. To stop bleeding caused by impaired blood coagulation, transfusion of fresh frozen plasma, prothrombin complex or cryoprecipitate is effective.
• Hemolysis warning. Treatment and prevention of hemolytic anemia is carried out with glucocorticosteroids (prednisolone), folic acid preparations, intravenous administration of human immunoglobulin. In severe cases, immunosuppressants are used - hydroxyurea, cyclosporine.
• Treatment of oncohematological diseases. For the treatment of erythroblastic leukemia, courses of chemotherapeutic agents (daunorubicin, vincristine) are prescribed. In order to suppress abnormal hematopoiesis in patients with polycythemia vera, interferon-alpha drugs, busulfan, ruxolitinib are used.

Surgery

Massive incessant bleeding requires surgical intervention - ligation, clipping of blood vessels, endoscopic hemostasis (electro-, cryo- or laser coagulation). The main treatment for many hemolytic anemias (hereditary microspherocytosis, sickle cell anemia, thalassemia) involves the removal of the spleen (splenectomy). 2 weeks before the operation, it is necessary to vaccinate against pneumococcus, meningococcus, Haemophilus influenzae. If conservative treatment of erythroblastic leukemia is ineffective, hematopoietic stem cell transplantation is performed.

Forecast

It is impossible to predict the prognosis by the level of reticulocytosis, the outcome is directly determined by the type and severity of the underlying pathology. Physiological reticulocytosis in neonates or after supplementation with folic acid, iron, and vitamin B12 is benign. Congenital heart defects, hemoglobinopathies or oncohematological diseases are characterized by a high percentage of deaths. If prolonged reticulocytosis is detected, it is necessary to consult a specialist to clarify the cause and select the treatment.