Why macrocytic anemia

This test can help spot early macrocytic or microcytic changes to your red blood cells. Additional blood tests can also help find the cause of your macrocytosis and anemia. This is important because treatment depends on the underlying cause. While nutrient deficiencies cause most macrocytic anemias, other underlying conditions may cause the deficiencies. Your doctor will run tests to check your nutrient levels. They may also do blood tests to check for alcohol use disorder, liver disease, and hypothyroidism.

Your primary care doctor may also refer you to a hematologist. Hematologists specialize in blood disorders. They can diagnose the cause and specific type of your anemia. Treatment for macrocytic anemia focuses on treating the cause of the condition. The first line of treatment for many people is correcting nutrient deficiencies.

This can be done with supplements or foods like spinach and red meat. You may be able to take supplements that include folate and other B vitamins. Most cases of macrocytic anemia that are caused by vitamin B and folate deficiencies can be treated and cured with diet and supplements. However, macrocytic anemias can cause long-term complications if left untreated. These complications can include permanent damage to your nervous system.

Extreme vitamin B deficiencies may cause long-term neurologic complications. They include peripheral neuropathy and dementia. However, you can prevent the anemia from becoming severe in most cases. Try these tips:. If you have anemia, your level of red blood cells is lower than normal. Chronic anemia results from long-term health conditions that affect your…. In nonmegaloblastic macrocytosis, the marrow is not megaloblastic, but in myelodysplasia and advanced liver disease there are megaloblastoid RBC precursors with dense nuclear chromatin that differ from the usual fine fibrillar pattern in megaloblastic anemias.

Vitamin B12 deficiency Vitamin B12 Deficiency Dietary vitamin B12 deficiency usually results from inadequate absorption, but deficiency can develop in vegans who do not take vitamin supplements.

Folate deficiency Folate Deficiency Folate deficiency is common. The most common cause of B12 deficiency is pernicious anemia due to impaired intrinsic factor secretion usually secondary to the presence of autoantibodies—see Autoimmune Metaplastic Atrophic Gastritis Autoimmune Metaplastic Atrophic Gastritis Autoimmune metaplastic atrophic gastritis is an inherited autoimmune disease that attacks parietal cells, resulting in hypochlorhydria and decreased production of intrinsic factor.

Pernicious anemia can develop even in the absence of old age. Other common causes are malabsorption due to gastritis, gastric bypass, or tapeworm infection. Dietary deficiency is rare but can occur in patients eating a vegan diet. Folate deficiency is exceedingly rare in countries where cereals and grains are fortified with folic acid. However, folate deficiency can occur in patients with restrictive diets, chronic alcohol use, or anorexia.

Malabsorptive conditions such as celiac disease Celiac Disease Celiac disease is an immunologically mediated disease in genetically susceptible people caused by intolerance to gluten, resulting in mucosal inflammation and villous atrophy, which causes malabsorption Diagnosis is clinical and by small-bowel biopsy.

Symptoms depend on the length and When folate requirement is increased, including during pregnancy and in patients with chronic hemolysis ie, hemoglobinopathies folate deficiency may occur.

Other causes of megaloblastosis include drugs generally antineoplastics such as hydroxyurea , or immunosuppressants that interfere with DNA synthesis and rare metabolic disorders eg, hereditary orotic aciduria.

Megaloblastic states result from defective DNA synthesis. RNA synthesis continues, resulting in a large cell with a large nucleus. All cell lines have dyspoiesis, in which cytoplasmic maturity is greater than nuclear maturity; this dyspoiesis produces megaloblasts in the marrow before they appear in the peripheral blood. Dyspoiesis results in intramedullary cell death, making erythropoiesis ineffective.

Because dyspoiesis affects all cell lines, reticulocytopenia and, during later stages leukopenia Overview of Leukopenias Leukopenia is a reduction in the circulating white blood cell WBC count to read more and thrombocytopenia Overview of Platelet Disorders Platelets are cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes, Macro-ovalocytes enter the circulation.

Hypersegmentation of polymorphonuclear neutrophils is common. Howell-Jolly bodies residual fragments of the nucleus are usually present. If iron deficiency or impaired iron utilization is present simultaneously, macrocytosis may not develop. Megaloblastic anemia develops insidiously and may not cause symptoms until anemia is severe. Gastrointestinal manifestations are common, including diarrhea, glossitis, and anorexia. Neurologic manifestations, including peripheral neuropathy and gait instability, are unique to B12 deficiency and can be permanent if prolonged.

Paresthesias can be the presenting manifestation of B12 deficiency, even before or in the absence of anemia. Megaloblastic anemia is suspected in anemic patients with macrocytic indices. Diagnosis is usually based on peripheral smear Peripheral smear Anemia is a decrease in the number of red blood cells RBCs—as measured by the red cell count, the hematocrit, or the red cell hemoglobin content.

In men, anemia is defined as hemoglobin read more. The RDW is high. In , global anemia prevalence was Thus, this review summarizes the diagnosis and treatment of macrocytic anemias in adults. The cause of macrocytic anemia is classified into one of the following categories, megaloblastic or nonmegaloblastic.

Megaloblastic anemia is caused by deficiency or impairment of utilization of vitamin B12 or folate. Nonmegaloblastic anemia may be the result of liver dysfunction, alcoholism, myelodysplastic syndrome MDS , or hypothyroidism. Common causes of macrocytosis are different by region and setting.

Vitamin B12 deficiency is the most common cause of megaloblastic anemia. Vitamin B12 deficiency is caused by insufficient dietary intake, as in the cases of vegetarians or malnutrition, malabsorption due to the absence of intrinsic factor caused by pernicious anemia or following gastric surgery, congenital disorders, such as transcobalamin II deficiency, or exposure to nitrous oxide.

Vitamin B12 binds to intrinsic factor secreted by the gastric parietal cells, and it is absorbed in the terminal ileum. Once absorbed, vitamin B12 acts as a coenzyme in the enzymatic reaction that produces methionine from homocysteine. As a result, folic acid is converted into its active form. When vitamin B12 is deficient, active folic acid is also deficient. As a result, the intracellular reaction involving the coenzyme form of folic acid is affected.

Thus, not only vitamin B12 but also folate deficiencies impair DNA synthesis. The signs and symptoms induced by megaloblastic anemia due to vitamin B12 deficiency are fatigue, headache, palpitations, and dyspnea, and neurological symptoms such as dysesthesia and hypoesthesia may also be present. In severe cases, ataxia, decreased proprioception, and vibratory sensation, collectively known as subacute combined degeneration, may be present.

Neurologic symptoms are not generally seen in folate deficiency. Vitamin B12 deficiency does not necessarily lead to anemia and macrocytosis. Other symptoms include Hunter's glossitis and gray hair. Peripheral blood smear reveals macrocytic anemias and pancytopenia, and hypersegmented neutrophils may be present in severe cases.

Megaloblastic changes in erythroblasts and giant metamyelocytes are seen in bone marrow, resulting from impaired nuclear differentiation. Biochemical analysis of blood shows increased levels of indirect bilirubin and lactate dehydrogenase LDH , and a decreased level of haptoglobin.

Vitamin B12 deficiency is treated with parenteral administration of vitamin B12, and hematological levels generally return to normal within one month. For patients with a permanent decrease in the ability to absorb dietary vitamin B12, such as associated with pernicious anemia or total gastrectomy, lifelong treatment is necessary.

Pernicious anemia is caused by autoimmune metaplastic atrophic gastritis AMAG , which predominantly manifests in the stomach body and fundus. Helicobacter pylori H. However, Hershko et al. The destruction of parietal cells leads to decreased acid production and intrinsic factor secretion, and autoantibodies against intrinsic factor inhibit the absorption of vitamin B Patients with pernicious anemia are at high risk of developing gastric adenocarcinoma and carcinoid tumors.

Folic acid is contained in green vegetables and animal products, such as liver. Folate deficiency may increase the risk of a congenital neural tube stenosis during pregnancy.

Folic acid is absorbed in the upper jejunum by both passive diffusion and active uptake. Folate deficiency is caused by nutritional deficiency eg, poor diet, alcoholism , malabsorption eg, celiac disease, inflammatory bowel disease , increased requirements eg, pregnancy, lactation, chronic hemolysis , or medication eg, methotrexate, trimethoprim, phenytoin.

Because serum folate levels fluctuate with dietary intake, measurement of RBC folate levels, which reflect folate stores in tissue, has been considered more reliable. MDS is defined as a clonal hematopoietic stem cell disorder characterized by cytopenia, myelodysplasia, ineffective hematopoiesis, and increased risk of progression to acute myeloid leukemia AML. Peripheral blood examination reveals cytopenia resulting from ineffective hematopoiesis.

MDS is classified according to the WHO classification system based on a combination of morphology, immunophenotype, genetics, and clinical features. Treatments are selected based on the MDS subtype and patient age. Patients who are under 55 years of age with severe bone marrow failure or high risk of developing AML may receive allogeneic hematopoietic stem cell transplantation.

Chronic consumption of more than 80 grams of alcohol per day has adverse effects on the hematologic system. Abstinence from alcohol rapidly returns elevated MCV 26 to normal levels. Anemia associated with hypothyroidism is usually normocytic or macrocytic. Because thyroid hormone stimulates the production of erythropoietin and affects hematopoiesis, a reduction in thyroid hormone production may cause anemia. Many drugs cause megaloblastic anemia by impairing the cellular availability or the utilization of folic acid or vitamin B Once macrocytosis has been identified, differential diagnosis should begin with determining the serum levels of vitamin B12 and folate and examining the peripheral blood smear Figure 1.

Macrocytic cells are red blood cells larger than the nucleus of a small lymphocyte. Flowchart for the differential diagnosis of macrocytic anemias MDS , myelodysplastic syndrome. Serum concentrations of homocysteine as well as serum concentrations of MMA are elevated in vitamin B12 deficiency, whereas only homocysteine is elevated in folate deficiency. When vitamin B12 or folate deficiency is ruled out, a reticulocyte count should be obtained.

Reticulocytes are immature nonnucleated erythrocytes. High levels of indirect bilirubin and LDH, and decreased levels of haptoglobin suggest the presence of hemolytic anemia. If hemolysis is not present, acute blood loss should be included in the differential diagnosis. The absence of reticulocytosis suggests the possibility of alcoholism, liver dysfunction, hypothyroidism, or MDS.

Of importance is the indication for bone marrow examinations. This is recommended for patients with abnormal cells in blood circulation or patients who do not respond to treatments, such as vitamin replacement.