Megaloblastic anemia: causes, symptoms, diagnosis, treatment

Megaloblastic anemia is the result of a deficiency of vitamin B ₁₂ and folic acid. Ineffective hematopoiesis affects all cell lines, but in particular erythroid. The diagnosis is based on a general blood test, a smear of peripheral blood, in which macrocytic anemia with anisocytosis and poikilocytosis is determined, large oval red blood cells (macrovalocytes), hyper-segmentation of neutrophils and reticulocytopenia. Treatment is aimed at eliminating the underlying cause.

Macrocytes are called enlarged erythrocytes (MCV> 95II). Macrocytic erythrocytes are found in various diseases, many of which are not associated with megaloblasticosis and the development of anemia. Macrocytosis can be caused by megaloblasts or other enlarged erythrocytes. Megaloblasts are large nucleated precursors of erythrocytes containing non-condensed chromatin. Megaloblastosis precedes the development of macrocytic anemia.

[1], [2], [3], [4], [5]

Causes of the megaloblastic anemia

The most common cause of interoblast hemopoiesis is a disruption of the utilization of vitamin B ₁₂ or folic acid. Other reasons include the use of medications (usually cytostatic or immunosuppressant drugs) that disrupt the synthesis of DNA, and less often metabolic diseases. In some cases, the etiology of megaloblasticosis is unknown.

[6], [7], [8], [9], [10]

Pathogenesis

Megaloblast type of hematopoiesis is the result of a violation of DNA synthesis, leading to the appearance of large cells with large nuclei. In all cell lines, there is a disruption in maturation, in which the maturation of the cytoplasm outstrips the maturation of the nuclei, this leads to the appearance of megaloblasts in the bone marrow before changes in blood take place. Violation of hemopoiesis causes bone marrow cell death, making erythropoiesis ineffective, and indirect hyperbilirubinemia and hyperuricemia. Since disruption of maturation affects all cell lines, reticulocytopenia is determined, in later stages of leukopenia and thrombocytopenia. Large oval erythrocytes (macro-ovalocytes) appear in the bloodstream. Characterized by hypersegmented polymorphonuclear neutrophils, the mechanism of their formation is unclear.

[11], [12]

Symptoms of the megaloblastic anemia

Anemia develops gradually and can be asymptomatic until it becomes pronounced. Deficiency of vitamin B ₁₂ can lead to the manifestation of neurological symptoms, including peripheral neuropathy, dementia and subacute combined degeneration. Deficiency of folic acid can cause the development of diarrhea, glossitis, weight loss.

Most macrocytic (MCV> 95 fl / cell) anemia are interregular. Non-agglutinous macrocytosis occurs with different clinical conditions, not all of which are clear. Anemia usually develops by mechanisms that do not depend on macro-cytosis. Macrocytosis, caused by an excess of the erythrocyte membrane, is manifested in patients with chronic liver disease, in which the esterification of cholesterol is impaired. Macrocytosis with MCV from 95 to 105 95 A / cell is manifested in chronic alcoholism with no deficiency of folic acid. Moderately expressed macrocytosis occurs in aplastic anemia, especially during the recovery period. Macrocytosis is typical for myeloid dysplasia. Because erythrocytes modify their shape in the spleen after exiting the bone marrow, macrocytosis can occur after splenectomy, although these changes are not associated with anemia.

Non-agglutinous macrocytosis is suspected in patients with macrocytic anemia who, after carrying out studies, are excluded from deficiency of vitamin B ₁₂ and folic acid. Macro-ovalocytes in the smear of peripheral blood and an increase in RDW, which is typical of classical megaloblastic anemia, may be absent. If non-aglobular macrocytosis is not clinically explained (for example, in the presence of aplastic anemia, chronic liver disease or alcohol use) or with suspected myelodysplasia, cytogenetic studies and bone marrow examination are necessary to exclude the presence of myelodysplasia. With nonglaoblastic macrocytosis in the bone marrow, megaloblasts are not detected, but myelodysplasia and pronounced liver damage are characterized by megaloblastoid precursors of erythrocytes with dense chromatin condensates, which differ from the usual thin threads characteristic of megaloblastic anemias.

Diagnostics of the megaloblastic anemia

The presence of megaloblastic anemia is expected in patients with anemia and macrocytic erythrocyte indices. The diagnosis is usually based on the study of the smear of peripheral blood. With a complete picture of anemia, macrocytosis occurs with MCV> 100fl. In the smear, ovalocytosis, anisocytosis and poikilocytosis are observed. The value of the spread of red blood cells by volume (RDW) is high. Howell-Jolli bodies (fragments of nuclei) are often encountered. The reticulocytopenia is determined. Hypersegmentation of granulocytes, later neutropenia, is developing early. In severe cases, thrombocytopenia is common, and platelets may have variations in size and shape. In unclear cases, it is necessary to perform a bone marrow examination.

[13], [14], [15], [16], [17], [18]

Treatment of the megaloblastic anemia

Before the beginning of treatment, the cause of anemia should be established. If there is a megaloblastic anemia, a vitamin B ₁₂ deficiency or folic acid deficiency is suggested . If there is insufficient data based on the study of peripheral blood and bone marrow, it is necessary to determine the level of vitamin B ₁₂ and folic acid.

Treatment depends on the cause that caused the anemia. Drugs that cause a megaloblastic state, it is necessary to cancel or reduce the dose.