Megaloblastic Anemia

What is Megaloblastic Anemia?

Megaloblastic anemia (MA) is a form of anemia that is caused by suppression of DNA synthesis in the production of red blood cells. When the DNA synthesis is hampered, cell cycle cannot proceed from G2 growth stage to mitosis or M stage. This causes continuation of cell growth without cell division that presents itself as macrocytosis.

The condition is also known as Megaloblastic Anaemia. MA belongs to the macrocytic classification.

Hypovitaminosis is most often the main cause behind the impairment of red cell DNA production. A deficiency of folic acid or vitamin B12 is commonly associated with this impairment. However, a deficiency in vitamin B12 alone is not going to cause MA if folate is present in sufficient levels. The actual mechanism involves loss of vitamin B12-dependant folate recycling, which is then followed by a folate-deficiency loss of the nucleic acid synthesis (more specifically, thymine), that leads to a malfunctioned DNA synthesis. Other factors might include copper deficiency and loss of micronutrients. The condition of megaloblastosis can be characterized by the presence of a high number of megaloblasts or large, dysfunctional and immature red blood cells in bone marrow as well as by hypersegmented neutrophils.

Megaloblastic Anemia Causes

A number of factors might lead to the development of MA. These include the following:

1. Vitamin B12 deficiency that leads to folate deficiency:

  • Coeliac disease
  • Deficient intake
  • Chronic pancreatitis
  • Ileal resection and bypassing
  • Achlorhydria-induced malabsorption
  • Deficient intrinsic factor (gastrectomy or pernicious anemia)
  • Nitrous oxide anesthesia (this normally requires repeated instances)
  • Selective Vitamin B12 malabsorption (drug-induced anemia, congenital anemia and juvenile megaloblastic anemia )
  • Biologically induced competition for Vitamin B12 by fistula, intestinal anastomosis, diverticulosis, and infection by marine parasite Diphyllobothrium latum

2. Deficiency of folate:

  • Alcoholism
  • Deficient intake
  • Jejunal and intestinal resection
  • Malabsorption (drug-induced and congenital)
  • Causes of increased needs, such as pregnancy, infant, cirrhosis and rapid cellular proliferation
  • Deficiency of thiamine and other factors like enzymes that are responsible for the metabolism of folate

3. Combined deficiency of Vitamin B12 and folate

  • Inherited DNA Synthesis Disorders
  • Inherited Pyrimidine Synthesis Disorders like Orotic aciduria
  • Drugs and Toxins
    • Phenytoin
    • Nitrous Oxide
    • Anticonvulsant drug dilantin
    • Folic acid antagonists like methotrexate
    • Pyrimidine antagonists like cytosine arabinoside
    • Purine synthesis antagonists like 6-mercaptopurine
    • Chemotherapy drugs like trimethoprim or azathioprine
  • Erythroleukemia
  • Leukemia
  • Myelofibrosis
  • Myelodysplastic syndrome
  • HIV Infection

Pathophysiology of Megaloblastic Anemia

Defective DNA synthesis in rapidly dividing cells is the most common feature of Megaloblastosis. RNA as well as protein synthesis are also impaired to a lesser extent. Impaired cell division and unbalanced cell growth occur due to halted nuclear maturation. More of the mature RBC precursors get destroyed in bone marrow before entering the blood stream of patients, in a process known as intramedullary hemolysis.

The most common factors responsible for MA include:

      • Medications
      • Cobalamin and folate deficiencies
      • Myelodysplastic disorders
      • Hindrance of DNA synthesis due to HIV infections

Megaloblastic Anemia Symptoms

The following symptoms are most commonly seen in the patients of this form of anemia. However, the symptoms can be slightly different in each patient. The typical signs include:

      • Fatigue
      • Anemia
      • Weakness
      • Weight loss
      • Decreased appetite
      • Loss of coordination
      • Changes in taste perception
      • Painful tingling of hands and feet
      • Smoothness and tenderness of tongue
      • Gastrointestinal problems like diarrhea
      • Irritability and changes in mental status

Megaloblastic Anemia Diagnosis

Doctors can suspect MA from general findings obtained from an overall physical examination and the study of the medical history of the child. In addition to this, numerous blood tests can also be performed in order to confirm diagnosis of megaloblastic anemia. If a digestive tract problem is believed to be responsible for the occurrence of this disorder, a doctor might recommend barium study of the digestive system. Other tests include checking the levels of folic acid and vitamin B12. Bone marrow biopsy, although not usually necessary, may be conducted in some cases.

Megaloblastic Anemia Treatment

While treating MA, it is firstly necessary to determine the underlying factors responsible for vitamin B12 and/or folate deficiency. This helps to plan adequate long-term treatment of the disorder for patients.

Sufferers are given Vitamin B12 injections daily for 1 week, then on a weekly basis for 4 weeks, and finally on a monthly basis until the vitamin levels are stabilized. Patients having a continued deficiency risk should be regularly treated with their monthly injections. Some sufferers may also be treated with oral vitamin B12 pills.

Oral folic acid pills can be administered for several months to cure Folic acid deficiency.

Alcohol should be avoided by the patients while treatment is on. Psychiatric treatment accompanied by substance abuse counseling should be administered to the patients if necessary.

Megaloblastic Anemia Complications

MA patients bear a risk of developing anemia-related cardiac complications and Hypokalemia that can be caused by therapy for cobalamin deficiencies.

Megaloblastic Anemia and Pregnancy

Folate deficiencies at the time of pregnancy might cause neural tube defects or other developmental anomalies in the fetus. However, these morbidities can be reduced by administering folate in the prenatal vitamins that can be given during pregnancy.

Megaloblastic Anemia Prognosis

The outcome can be promising for MA patients if the underlying causes behind megaloblastosis are identified and proper treatment measures are opted for.

Megaloblastic Anemia Pictures

Check out the images of Megaloblastic Anemia sufferers.

Picture of Megaloblastic Anemia

Picture 1 – Megaloblastic Anemia

Image of Megaloblastic Anemia

Picture 2 – Megaloblastic Anemia Image

It is important to find out the underlying reasons behind such deficiencies, which makes treatment effective and easier. The condition can be completely cured over time and the patients can live a healthy, normal life.

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