macrocytic anemia



Anemia is a condition in which the average red blood cell volume is greater than 100 fl.

Anemia in which the mean red blood cell volume is greater than 100 fl. It is characterized by pallor, weakness, tongue inflammation, numbness of the hands and feet, and sensory disturbances, and is caused by vitamin B12 or folic acid deficiencies, medication use, and certain diseases, including treatment of the cause of the disease, general treatment, and complementary medicine.

Definitions

Macrocytic anemia is defined as anemia with a mean corpuscular volume (MCV) >100 fl.

The current diagnostic criteria for anemia in China are hemoglobin (Hb) less than 120 g/L for adult men, less than 110 g/L for adult women, and less than 100 g/L for pregnant women in sea level areas.

Normal range of MCV: 80.0 to 93.6 fl (males); 77.7 to 93.7 fl (females).

Classification

It can be categorized according to the etiology:

Megaloblastic anemia: due to deficiency of vitamin B12 and/or folic acid, resulting in impaired deoxyribonucleic acid (DNA) synthesis in red blood cells.

Non-megaloblastic macrocytic anemia: commonly caused by myelodysplastic syndromes (MDS), chronic aplastic anemia (AA), hemolytic anemia (HA), alcoholism, and liver disease.

Causes

Causes

Abnormal DNA metabolism (megaloblastic anemia)

Folate deficiency

Decreased intake: mainly due to the destruction of large amounts of folic acid by poor cooking methods such as too long cooking time or too high temperature; secondly, due to partiality (reduction of vegetables, meat and eggs in food).

Increased need: folic acid need will be increased during pregnancy, children and adolescents in growth and development, chronic recurrent hemolysis, leukemia, tumors, hyperthyroidism, long-term hemodialysis treatment of the population.

Absorption disorders: Diarrhea, small bowel inflammation, tumors and surgery and certain drugs (anti-epileptic drugs, salazosulfapyridine, etc.), ethanol can lead to folic acid absorption disorders.

Utilization disorders: anti-DNA synthesis drugs such as methotrexate, methotrexate, aminopterin, aminopterin and ethylaminopyrimidine can lead to folate utilization disorders; some congenital enzyme defects can also affect the utilization of folic acid.

Increased excretion of folic acid: hemodialysis, alcoholism and other factors can lead to increased excretion of folic acid.

Decreased intake: It is rare that it is purely caused by insufficient intake, and is only seen in people who have been on a strict vegetarian diet for a long period of time.

Impaired absorption: is the most common cause and can be due to endogenous factor deficiencies (e.g., pernicious anemia, gastrectomy, atrophic gastritis, etc.), gastric acid and pepsin deficiencies, chronic pancreatic disease, ileal disorders, medications (para-aminosalicylic acid, neomycin, metformin, colchicine, etc.), intestinal parasites (e.g., broad-sectioned lissencephalomatous cestodes), and depletion of vitamin B12 by bacterial proliferation.

Utilization disorder: congenital transdrill protein II deficiency, anesthetic nitrous oxide and other factors can cause vitamin B12 utilization disorder.

Antimetabolic drugs: use of 6-mercaptopurine, fluorouracil, hydroxyurea and cytarabine.

Certain genetic disorders: whey aciduria, Lesch-Nyhan syndrome, deficiency of iminomethyltransferase or N5-methyltetrahydrofolate transferase.

Abnormalities of red blood cell development

Reticulocytosis, e.g., hemolytic anemia, bone marrow recovery after chemotherapy or hematopoietic stem cell transplantation, increased erythropoiesis after use of erythropoietin and supplementation with iron, vitamin B12, or folic acid, and recovery from bleeding.

Aplastic anemia, Fanconi anemia.

Primary bone marrow disorders

Myelodysplastic syndromes, hereditary orocytosis, and large granular lymphocyte (LGL) leukemia can result in elevated erythrocyte volume.

Erythrocyte membrane lipid abnormalities

Liver disease, hypothyroidism can lead to mildly elevated erythrocyte volume.

Mechanisms are not known

Alcoholism, multiple myeloma, and other plasma cell disorders can cause elevated erythrocyte volume.

Risk Factors

People with any one or more of the following risk factors are at high risk for macrocytic anemia.

Poor dietary habits: low intake of vegetables, meat and eggs, long-term use of high-temperature cooking and other poor cooking methods leading to excessive destruction of nutrients in food.

Gastric diseases: long-term use of acid suppressants (such as omeprazole, ranitidine, etc.) or gastric surgery can lead to a decrease in gastric acid, causing impaired absorption of vitamin B12.

Pregnant women, children and adolescents: increased need for folic acid and vitamin B12.

Alcohol abuse: can affect the absorption and utilization of folic acid.

Symptoms

Main Symptoms

Hematologic symptoms

Anemia symptoms such as weakness, decreased activity tolerance, dizziness, palpitations.

Pallor, fine and sparse hair.

In severe cases of complete blood cell reduction, recurrent infections and bleeding, skin petechiae, ecchymosis, purpura, bleeding gums, nosebleeds, black stools and other manifestations may occur.

Some of them are accompanied by mild jaundice (yellowing of skin, mucous membranes and sclera).

Digestive system symptoms

There may be atrophy of oral mucosa and tongue papillae, with “beef-like tongue”, which may be accompanied by tongue pain.

Gastrointestinal symptoms such as lack of appetite, nausea, bloating, diarrhea or constipation may occur.

Neuropsychiatric symptoms

Symmetrical distal limb numbness, hypesthesia or loss of sensation may occur.

Poor motor coordination and unsteady gait.

Decreased sense of taste and smell.

Vision loss, blackout (blackness in front of the eyes when seeing objects, unable to see or see objects).

In severe cases, urinary and fecal incontinence.

People with folic acid deficiency have psychiatric symptoms such as irritability and paranoia.

Vitamin B12 deficiency patients have depression, insomnia, memory loss, delirium, hallucinations, delusions and even insanity, personality perversion.

Urinary and reproductive system symptoms

Polyuria, proteinuria, menstrual disorders (amenorrhea), loss of libido and other manifestations may occur.

Complications

Hemolysis

Hemolysis can be caused by heterogeneous red blood cells.

Fever, chills, back pain, jaundice, oliguria, anuria may occur.

Heart failure

It can lead to myocardial ischemia and hypoxia, causing a decrease in cardiac output and inducing heart failure.

Symptoms such as dyspnea, cough, sputum and edema may occur.

Consultation

Department of Medicine

Hematology

If you have symptoms such as pallor, fatigue, decreased activity tolerance, dizziness, palpitations, etc., or if anemia is detected in your routine physical examination, it is recommended that you consult the Department of Hematology.

Other corresponding departments

If symptoms such as loss of appetite, nausea, or diarrhea occur, consult the Department of Gastroenterology.

If there is numbness or loss of sensation in the limbs, consult the Department of Neurology.

If you experience vision loss or blackouts, consult an ophthalmologist.

If there is depression, insomnia, memory loss, you can go to psychiatry.

In addition, you can visit Nephrology, Urology and Gynecology according to your symptoms.

Preparation for medical treatment

Preparing for your visit: registering, preparing information, and common problems.

Tips for medical treatment

It is recommended to rest in bed before seeking medical treatment to avoid falling due to dizziness.

Preparation List

Symptom list

Pay particular attention to the time of onset of symptoms, special manifestations, etc.

Are there symptoms such as fatigue, decreased activity tolerance, dizziness, palpitations, etc.?

Are there any symptoms such as sore tongue?

Are there any symptoms such as lack of appetite, nausea, bloating, diarrhea or constipation?

Are there any symptoms such as symmetrical distal limb numbness, deep sensory deficits, ataxia or unsteady gait?

Is there any decrease in the sense of taste or smell?

Is there any vision loss or blackout?

Is there incontinence of urine or faeces?

Any mental symptoms such as irritability, delusions, depression, insomnia, memory loss, delirium, hallucinations, etc.?

Are there any symptoms such as polyuria, menstrual disorders (amenorrhea), loss of libido?

How long have these symptoms been present?

List of medical history

Are there any poor cooking practices such as cooking food for too long or at too high a temperature?

Are there any poor dietary habits that are low in vegetables, meat and eggs?

Are there any blood disorders such as hemolytic anemia, aplastic anemia, myelodysplastic syndrome, etc.?

Any history of tumor, thyroid dysfunction, long-term hemodialysis treatment, etc.?

Is there any history of diarrhea, small bowel inflammation, etc.?

Are there any gastric disorders such as gastrectomy, atrophic gastritis, gastric acid and pepsin deficiency?

Are there any liver disorders?

Are there any other hereditary diseases?

Is there alcoholism?

Checklist

Test results of the last six months, which can be brought to the doctor’s office

Laboratory tests: routine blood tests, bone marrow cytology tests, etc.

Medication List

Medication in the last 3 months, if available in boxes or packages, bring with you to the doctor’s office

Megaloblastic anemia supplemental therapy drugs: vitamin B12, folic acid, etc.

Chemotherapy drugs: cytarabine, capecitabine, fluorouracil, etc.

Antiretroviral drugs: zidovudine, etc.

Gastric acid inhibitors: omeprazole, ranitidine, etc.

Others: para-aminosalicylic acid, neomycin, metformin, allopurinol, etc.

Diagnosis

Diagnosis is based on

Medical history

The following medical history may precede the onset of the disease:

There are poor cooking practices such as excessive cooking time or temperature.

There is a poor diet with low intake of vegetables, meat and eggs.

History of blood disorders such as hemolytic anemia, aplastic anemia, and myelodysplastic syndrome.

Have a history of tumors, abnormal thyroid function, and long-term hemodialysis treatment.

History of diarrhea, small bowel inflammation, etc.

History of gastric diseases such as gastrectomy, atrophic gastritis, gastric acid and pepsin deficiency.

Have a history of liver disease.

History of alcohol abuse.

History of drug taking.

Clinical manifestations

Symptoms

Hematologic symptoms: pallor, weakness, decreased activity tolerance, dizziness, palpitations, etc.

Digestive system symptoms: tongue pain, lack of appetite, nausea, bloating, diarrhea or constipation, etc.

Neurological symptoms: symmetrical distal limb numbness, deep sensory impairment, ataxia or unsteady gait, decreased sense of taste and smell, decreased visual acuity, blackouts, urinary and fecal incontinence.

Mental symptoms: irritability, delusion, depression, insomnia, memory loss, delirium, hallucinations, etc.

Urinary and reproductive symptoms: polyuria, menstrual disorders (amenorrhea), decreased libido, etc.

Physical signs

Pale skin on nail beds, mucous membranes of mouth and lips and lid conjunctiva.

Atrophy of oral mucosa and tongue papillae, “beef-like tongue”.

Involvement of the nervous system may result in positive pyramidal signs, increased muscle tone, and hyperreflexia.

Laboratory Tests

Blood tests

Evaluate peripheral blood erythrocytes, leukocytes, and platelets.

A mean corpuscular volume (MCV) of >100fl and a lower than normal hemoglobin may be present; peripheral blood smears suggest neutrophilic lobularity and large ovoid red blood cells.

Fasting is not required for routine blood tests.

Determination of reticulocytes

To understand the reticulocytes in peripheral blood, which indirectly reflects the proliferation of bone marrow erythroid system.

Reticulocytes >2% are indicative of acute hemorrhagic anemia, hemolytic anemia, megaloblastic anemia, and certain anemias after treatment, e.g., after iron or vitamin B12 and folic acid supplementation.

Reticulocytes less than 2% and a mildly elevated MCV (100-110fl) suggests non-megaloblastic macrocytic anemia due to liver disease, aplastic anemia, myelodysplastic syndromes, and others.

Bone marrow cytology

To understand the proliferation of erythroid, granulocytic and megakaryocytic cells in bone marrow and to identify the cause of the disease.

Visible: active or apparently active proliferation, red lineage proliferation is significant, megaloblastic macrocytic anemia can be megaloblastic (cytosol is large, cytoplasm is more mature than the nucleus, “nucleus is young and plasma is old”), the granulocytic lineage is also megaloblastic, and the mature granulocytes are more lobed; megakaryocytes are increased in size and excessively lobed.

Know the serum levels of vitamin B12 and folic acid.

Serum vitamin B12 below 100pg/ml suggests vitamin B12 deficiency; serum folic acid below 3ng/ml and erythrocyte folic acid below 100ng/ml suggests folic acid deficiency.

Note: A simple decrease in serum folate or vitamin B12 levels is not a basis for a definitive diagnosis.

It helps to determine the cause of vitamin B12 deficiency.

Positive to consider the possibility of pernicious anemia.

Thyroid Function Measurement

To find out if thyroid function is normal and used to determine the cause of macrocytic anemia.

Elevated T4 levels and decreased TSH levels suggest hyperthyroidism, while elevated TSH suggests hypothyroidism.

Liver Function Test

Used to assess liver function and to rule out liver disease.

Elevated ALT and AST suggest abnormal liver function and liver disease needs to be considered.

Grading

Can be graded according to the degree of hemoglobin (Hb) decline:

Mild anemia: Hb greater than 90g/L but below the lower limit of normal reference value.

Moderate anemia: Hb 61 to 90g/L.

Severe anemia: Hb 31～60g/L.

Very severe anemia: Hb ≤ 30g/L.

Differential Diagnosis

Normocytic anemia

Similarity: both can cause anemia symptoms such as pallor, weakness, decreased activity tolerance, dizziness, palpitations, etc.

Differences: normocytic anemia has normal red blood cell morphology, normal MCV, and can be differentiated by blood routine.

Microcytic anemia

Similarity: Anemia symptoms such as pallor, fatigue, decreased activity tolerance, dizziness, palpitations, etc. may occur.

Differences: microcytic anemia is more common in iron deficiency anemia, iron granulocytic anemia, pearl protein anemia, etc. MCV is reduced and blood routine can be differentiated.

Treatment

Treatment objective: timely removal of the cause, correction of anemia, relief of symptoms, prevention of complications.

Treatment principle: actively remove the cause if there is a clear cause, and cooperate with general treatment.

Acute stage treatment

If the anemia is severe and the symptoms are obvious, transfusion of suspended red blood cells can be considered to correct the anemia.

General treatment

Remove the causative factors and improve the bad cooking and eating habits.

Alcoholics need to stop drinking.

In the acute phase, bed rest should be provided and activity should be reduced.

Etiologic treatment

Those with primary diseases, such as gastric diseases, liver diseases, hemolytic anemia, myelodysplastic syndrome, aplastic anemia, etc., need to actively treat the primary diseases.

Those caused by drugs should stop and change drugs as appropriate.

Supplementary drug therapy

For those with vitamin B12 deficiency.

It can be given intramuscularly or orally, and generally requires simultaneous supplementation of folic acid.

Precautions: For patients with gout, it can increase blood uric acid and induce gouty attacks; chloramphenicol, aminoglycosides, p-aminosalicylic acid and other drugs will affect the absorption, and simultaneous use should be avoided.

Folic acid

Including folic acid, calcium folinate.

Can be taken orally or injected intramuscularly.

Suitable for people with folic acid deficiency.

Note: If combined with vitamin B12 deficiency should be supplemented at the same time, otherwise there is a possibility of aggravating neurological damage.

Iron

Including: ferrous sulfate, ferrous fumarate and so on.

Applicable to the co-existence of iron deficiency.

Precautions: Oral administration may cause varying degrees of epigastric discomfort, nausea, vomiting, abdominal cramps, diarrhea or constipation.

Prognosis

Cure

Prognosis is related to the primary disease.

Most cases of megaloblastic anemia have a good prognosis and can be recovered after active treatment.

Those with pernicious anemia require lifelong treatment.

Those caused by malignant diseases such as tumors have a poor prognosis.

Hazards

It can lead to decreased activity tolerance, memory loss, and some cause neurological symptoms, affecting normal life and work.

Severe cases can bleed, and if the bleeding is large, it can lead to life-threatening hemorrhagic shock.

Hemolysis can occur, further leading to kidney function damage, and even life-threatening.

In severe cases, anemia can cause heart failure, which is life-threatening.

Megaloblastic anemia occurs during pregnancy and can affect fetal development.

Daily

Daily Management

Dietary management

Correct bad dietary habits, it is advisable to eat more fresh fruits and vegetables, meat, eggs and other foods to maintain balanced nutrition and avoid insufficient intake of vitamin B12 and folic acid.

Ensure daily intake of at least 400 grams of vegetables, dark green vegetables are recommended.

Vitamin B12 deficient people need to eat more animal liver, fish, poultry, eggs, shellfish.

Correct bad cooking habits, avoid long cooking time and high temperature.

Strictly abstain from alcohol.

Life management

Rest in bed, avoid strenuous exercise, and gradually resume activities only after symptoms improve.

Follow-up

Follow the doctor’s instructions for regular checkups so that the doctor can evaluate the condition and adjust the treatment plan.

Follow-up examinations generally include routine blood tests, reticulocyte tests, bone marrow cytology, vitamin B12 and folic acid tests.

Prevention

Adopt good dietary habits, avoiding partiality and poor cooking methods, and avoiding alcohol abuse.

Infants and young children should be given complementary foods in a timely manner. Adolescents and pregnant women should be given more fresh vegetables, meat and eggs, and small doses of oral folic acid or vitamin B12 should be taken for prevention if necessary.

When treating with drugs that can cause macrocytic anemia, supplement folic acid and vitamin B12 in time and check regularly.

Actively treat the primary disease.