Megaloblastic anemias: causes, symptoms, diagnosis, treatment

Megaloblastic anemias result from vitamin B12 and folate deficiency _. Ineffective hematopoiesis affects all cell lines, but especially the erythroid line. Diagnosis is based on a complete blood count and peripheral blood smear, which show macrocytic anemia with anisocytosis and poikilocytosis, large oval red blood cells (macro-ovalocytes), hypersegmentation of neutrophils, and reticulocytopenia. Treatment is aimed at eliminating the underlying cause.

Macrocytes are enlarged red blood cells (MCV > 95II). Macrocytic red blood cells are found in a variety of diseases, many of which are not associated with megaloblastosis and the development of anemia. Macrocytosis may be due to megaloblasts or other enlarged red blood cells. Megaloblasts are large nucleated precursors of red blood cells that contain uncondensed chromatin. Megaloblastosis precedes the development of macrocytic anemia.

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Causes megaloblastic anemia

The most common cause of interregional hematopoiesis is a disorder of utilization of vitamin B ₁₂ or folic acid. Other causes include the use of drugs (usually cytostatic or immunosuppressants) that disrupt DNA synthesis, and, less commonly, metabolic diseases. In some cases, the etiology of megaloblastosis is unknown.

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Pathogenesis

Megaloblastic hematopoiesis results from a defect in DNA synthesis, resulting in large cells with large nuclei. All cell lines show a maturation defect in which cytoplasmic maturation outpaces nuclear maturation, resulting in megaloblasts appearing in the bone marrow before changes occur in the blood. The defect in hematopoiesis causes bone marrow cell death, rendering erythropoiesis ineffective, and indirect hyperbilirubinemia and hyperuricemia. Since the maturation defect affects all cell lines, reticulocytopenia is present, with leukopenia and thrombocytopenia occurring later. Large oval red blood cells (macro-ovalocytes) appear in the circulation. Hypersegmented polymorphonuclear neutrophils are characteristic, the mechanism of which is unclear.

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Symptoms megaloblastic anemia

Anemia develops gradually and may be asymptomatic until it becomes pronounced. Vitamin B12 deficiency _can lead to manifestation of neurological symptoms, including peripheral neuropathy, dementia, and subacute combined degeneration. Folic acid deficiency can cause diarrhea, glossitis, and weight loss.

Most macrocytic (MCV > 95 fl/cell) anemias are interregional. Nonmegaloblastic macrocytosis occurs in a variety of clinical conditions, not all of which are clear. Anemia usually develops by mechanisms independent of macrocytosis. Macrocytosis due to excess red cell membrane occurs in patients with chronic liver disease in which cholesterol esterification is impaired. Macrocytosis with MCV 95 to 105 95A/cell occurs in chronic alcoholism without folate deficiency. Moderate macrocytosis occurs in aplastic anemia, especially during recovery. Macrocytosis is also typical of myeloid dysplasia. Because red cells undergo shape modification in the spleen after leaving the bone marrow, macrocytosis may occur after splenectomy, although these changes are not associated with anemia.

_{Nonmegaloblastic macrocytosis is suspected in patients with macrocytic anemia in whom vitamin B12} and folate deficiency have been excluded by testing. Macroovalocytes in the peripheral blood smear and an elevated RDW, which are typical of classic megaloblastic anemia, may be absent. If nonmegaloblastic macrocytosis is clinically unexplained (eg, in the presence of aplastic anemia, chronic liver disease, or alcohol use) or if myelodysplasia is suspected, cytogenetic studies and bone marrow examination should be performed to exclude myelodysplasia. In nonmegaloblastic macrocytosis, megaloblasts are not detected in the bone marrow, but in myelodysplasia and advanced liver disease, megaloblastoid red cell precursors with dense chromatin condensates are characteristic, which differ from the usual thin filaments characteristic of megaloblastic anemias.

Diagnostics megaloblastic anemia

Megaloblastic anemia is suspected in patients with anemia and macrocytic indices of red blood cells. The diagnosis is usually based on the examination of a peripheral blood smear. In the complete picture of anemia, there is macrocytosis with MCV> 100fl. Ovalocytosis, anisocytosis and poikilocytosis are observed in the smear. The value of red blood cell dispersion by volume (RDW) is high. Howell-Jolly bodies (nuclear fragments) are often found. Reticulocytopenia is determined. Hypersegmentation of granulocytes develops early, neutropenia later. In severe cases, thrombocytopenia is common, and platelets may have abnormalities in size and shape. In unclear cases, a bone marrow examination should be performed.

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Treatment megaloblastic anemia

Before treatment, the cause of anemia must be established. If megaloblastic anemia is detected, vitamin B ₁₂ or folate deficiency is assumed. If peripheral blood and bone marrow tests are insufficient, vitamin B ₁₂ and folate levels must be determined.

Treatment depends on the cause of the anemia. Drugs that cause megaloblastic conditions should be discontinued or the dose should be reduced.