megaloblastic anemias



  • L & rsquo; anemia is to reduce the rate of & rsquo; hemoglobin below 13 g / dl in the & rsquo; man, 12g / dl in women and children, of 10.5g / dL in pregnant women, from 11 g / dL in infants and 14g / dL in the neonate
  • L’anémie macrocytaire définit des globules rouges “GR” large size, which MCV is greater than 100FL.
  • L & rsquo; megaloblastic anemia is macrocytic anemia characterized by the presence of & rsquo; abnormally large erythroblasts in bone marrow and are called megaloblasts.
  • It is in most cases linked to a deficiency antipemicieux factors (Vit B12 and folic acid)
  • But it can also be toxic or neoplastic origin.


  • In Algeria, before 1970, folic acid deficiency was by far the most common.
  • Currently, due to folic acid supplementation of pregnant women, its frequency is much reduced.
  • On the other hand, lives B12 deficiency is more frequent, probably related to the & rsquo; no limitation of this vitamin as a tonic. So, B12 deficiency is about lives 3% causes d & rsquo; anemia in the & rsquo; adult and is less common than iron deficiency, evaluated 40%.


The antipernicieux factors are represented by :

—> The lives B9 or folate (folic acid and derivatives thereof) :

  • Involved in the synthesis of & rsquo; DNA and thus in cell replication..
  • Folate is exclusively made by the & rsquo; polyglutamate form of power, present in many foods (green vegetables, dried fruits and fresh, foie, cereals, Egg yolk) and are destroyed by prolonged cooking.
  • L & rsquo; gastrointestinal absorption occurs in the proximal jejunum.
  • Daily requirements in the & rsquo; adults are estimated at 100 and 400qg / d and are largely covered by a normal diet but these requirements increase to over-growth and pregnancy.
  • The mainly liver reserves are low (10 at 15 mg) and represent a range of 3 at 4 month.

—> B12 or cobalamin saw :

  • Involved in the synthesis of methionine and in the conversion of & rsquo; methylmalonic acid succinic acid.
  • The deficit in the synthesis of & rsquo; DNA, observed in B12 deficiency lives n & rsquo; is not due to a direct mechanism, but appears to involve a blocking of folate metabolism, c & rsquo; is the trap folate.
  • The daily requirement of B12 lives are minimal estimated between 1 and 2 pg / d and are made primarily by animal proteins : foie, meats, the fish, eggs and dairy.
  • L & rsquo; gastrointestinal absorption occurs at the level of the & rsquo; distal ileum, after fixing the intrinsic factor (secreted by the parietal cells of the gastric mucosa) essential for the & rsquo; absorption of B12 lives ileal villi.
  • Plasma transportation is mainly due to a so-called protein Transcobalamin II.
  • L & rsquo; d & rsquo body has; large reserves in lives B12, mainly liver, estimated between 2 and 3 mg and representative 3 at 4 years & rsquo; autonomy. This explains the delayed nature of deficiencies lives B12.


—> megaloblastic deficiency anemia antipemicieux factors :

  • Failure synthesis & rsquo; DNA results in a reduction of mitosis, cause of gigantism erythroblasts, d & rsquo; where megaloblastosis.
  • These megaloblasts have an asynchronous development of nucleus and cytoplasm.
  • Another consequence is the & rsquo; ineffective hematopoiesis by intramedullary hemolysis.
  • Failure synthesis & rsquo; DNA also provides the granular cells and platelets. It s & rsquo; expressed by a polysegmentation PMN with macrothrombocytose.
  • There is also an atrophy of cells of the digestive mucosa and vaginal (trickplay cells) d & rsquo; where digestive disorders and reversible infertility.
  • In nerve cells, lives B12 deficiency causes defective synthesis of myelin by default methionine, to & rsquo; origin & rsquo; neuropathy by combined degeneration of the spinal cord.

—> Megaloblastic anemia d & rsquo; toxic origin :

It is due to taking certain antineoplastic or immunosuppressive drugs that are competitive inhibitors of the synthesis of & rsquo; DNA.

—> Megaloblastic anemia d & rsquo; neoplastic origin :

It is due to a anonfalie of hematopoietic stem cell.


A- anemic syndrome : d & rsquo; gradual installation

  1. Pale mucocutaneous.
  2. conjunctival jaundice.
  3. Dyspnea effort.
  4. Asthenia, up to the maximum confining the patient to bed, d & rsquo; hence the name & rsquo; pernicious anemia.

B- digestive syndrome : in connection with the & rsquo; atrophy of the digestive mucosa, is translated by

  1. Atrophic glossitis with dry mouth and burns in contact with hot and spicy food.
  2. A language & rsquo; depapillated first red and then smooth the edges, brilliant and totally depapillated, c & rsquo; is glossitis Hunter.
  3. Dyspeptic disorders with diarrhea rapidly regressing replacement therapy.

C- Syndrome neuro-anemic : electively occurring in the lives deficiency E12, it may precede the & rsquo; anemia but rarely isolated. It sends a table of combined degeneration of the cord with

  1. A pyramidal syndrome (sign bilateral Babinski, hyperéflexie O-T.)
  2. A posterior cord syndrome (muscle cramps, paresthésie, spinal intermittent claudication.)

D- other signs :

  1. reversible infertility in women and asthénospermie in the & rsquo; man.
  2. Hyperpigmentation skin especially at the palmar region.
  3. moderate splenomegaly.


A / Hémogramme : reveals

  • anemia (Hb between 3 et 10g/dl) – macrocytaire (VGM to sup lOOfl) – normochrome (CCMH normal.)
  • Normal or low reticulocyte.
  • Leukopenia and / or thrombocytopenia frequently associated, sometimes pancytopenia.

B / blood smear : GR reveals discrepancies with

  • Anisocytosis with GR ds large, poïkilocytose, polychromatophilie.
  • It also reveals abnormalities PNN that are large in size with a core hypersegmented, and giant platelets.

C / Médullogramme : watch

  • A rich marrow, intensely blue appearing (basophilia increased by synthesis of & rsquo; RNA)
  • An increase in the d & rsquo rates; erythroblasts and size or megaloblasts.
  • Asynchrony in Nucleo-cytoplasmic maturation megaloblasts where the cores are young with fine chromatin and & rsquo; mature hémoglobinisation.
  • Other signs of abnormal mitosis with dyserythropoiesis, polyploidy and presence Jolly body.
  • An increase in the size of myelocytes and metamyelocytes.

D / vitamin Assays :

  • useful but expensive.
  • they dosent serum folate (Vn = 5 to 15pig / 1) and erythrocyte (Vn = 200-400pg/l)
  • a decrease in erythrocyte rate reflects an important and ancient depletion so that & rsquo; a decrease in serum reflects a more recent deficit.
  • Note that for the lives B12, Vn = 200 to 500 ng / l

E / Other assays : shows signs of & rsquo; intramedullary hemolysis with

  • Increased serum free bilirubin.
  • Increased LDH.

F / therapeutic Tests :

  • Useful when dosages are impossible or not yet available.
  • They are to provide for daily and 3 days physiological doses of the suspected vitamin (lpg lives of B12 or lOOpg d & rsquo; folic acid.).
  • If in doubt, we first saw B12 to avoid the trap folate.
  • in case of vitamin deficiency, reticulocyte crisis is obtained between the 5th and the Tenth day and said the test is positive.


The definition of & rsquo; megaloblastic anemia being morphological, differential diagnosis poses few problems, however, some difficulties should be highlighted
—> Anemia megaloblastic macrocytic non- are observed in :
– regenerative anemia, secondary to massive bleeding or mostly haemolysis.
– in hypothyroidism, hepatic cirrhosis, the chronic alcoholism.
—> Macrocytic anemias marrow mégaloblastoïde :
– some aplastic, leukemia and acute myelodysplastic syndromes



1- food intake default : it can

  • Over and over malnutrition.
  • In the & rsquo; chronic alcoholism.
  • In infants when the exclusive milk diet is maintained too long.
  • In some eating habits (lack of green vegetables, Prolonged cooking systematically.)

2- Excess & rsquo; use : it can

  • In-pregnancy in multiparas, the twin pregnancy and & rsquo; breastfeeding.
  • Over and over the mostly chronic congenital hemolytic anemias, growth and cancer.

3- malabsorption digestive : it can

  • Over and over the proximal small bowel resection.
  • Over and over celiac disease and lymphoma.

4- congenital deficiencies : exceptional in folate metabolism.


  1. Failing & rsquo; s contribution: exceptional, respect strict vegetarians.
  2. malabsorption digestive: most common cause, may be
  • D & rsquo; gastric origin: In case of
  • Gastrectomie totale, sometimes partial. B12 deficiency occurs lives 4 at 5 years after the & rsquo; Intervention.
  • Gastritis nonspecific atrophic.
  • selective congenital deficiency of intrinsic factor.
  • Pernicious anemia:

– C & rsquo; is atrophic gastritis in & rsquo; origin & rsquo; malabsorption of B12 depletion lives secretion of intrinsic factor.
– It mainly affects women over 40 years and White.
– II s & rsquo; is d & rsquo; a condition autoimmune due to the production of & rsquo; auto-anti-intrinsic factor and anti-gastric parietal cells.
– It is often associated with d & rsquo; other autoimmune diseases, including vitiligo, diabetes and thyroid disorders (Basedow, thyroiditis d & rsquo; Hashimoto and myxedema.)
– The objective gastroscopy irreversible atrophy of the gastric mucosa.
– The gastric tube shows achylie with achlorhydric resistant to secretagogues, including pentagastrin with lack of intrinsic factor in gastric juice.
– The treatment lasts a lifetime and the possibility of & rsquo; a cancer-during the & rsquo; evolution requires an endoscopic all 2 years.

  • On intestinal origin: In case of
  • Surgical resection of the distal small.
  • Crohn's disease, intestinal lymphomas.
  • Syndrome & rsquo; Imerslund or selective malabsorption by congenital anomaly ileal receptor vitB12.
  • Congenital affecting transport or & rsquo; use, including the deficit Transcobalamin II.


when taken

  • cytotoxic drugs: which are competitive inhibitors of the synthesis of nucleic acids (Ex: Purinethol, Azothioprine, Hydrea.)
  • antifolate drugs (Ex: methotrexate, trimethoprim, etc.)
  • AEDs: cause malabsorption of folate (Ex: Hydantoïne, Gardenal.)
  • TB drugs: Cause folate deficiency.
  • Other: Colchicine, neomycin, Metformin which inhibit & rsquo; absorption of B12 lives.


  • O & rsquo; is watching with refractory anemias that are commonly macrocytic and megaloblastic.
  • Often, diagnosis n & rsquo; is mentioned that before the & rsquo; d & rsquo inefficiency, a vitamin therapy.
  • It can be confirmed by looking ringed sideroblasts Péris after staining smear spinal cord and / or an excess of myeloblasts.


A) But :

  • Correct & rsquo; anemia and other haematological abnormalities.
  • Restore vitamin reserves.
  • Treating & rsquo; causal affection.

B) Means :

– replacement therapy:

• Folic acid (Foldine*) Cp 5mg.

  • folinic acid (Lederfoline *) in Amp 50 mg IM or IV.
  • vitamin B12 (Hydroxocobalamine* ou Cyanocobalamine*) en Amp 1000 gg IM

– Symptomatic treatment :

  • Blood transfusion in case of & rsquo; poorly-tolerated anemia.

C) Indications :

  • In case of nutritional deficiency or & rsquo; increased need for folate : Foldine, 3 cp / day for 2 month.
  • If & rsquo; congenital haemolytic anemia : final discontinuously Treatment, is 2 Cp lj / 2
  • If malabsorption or d & rsquo disorders; use of folate : Lederfoline, 5 10mg 3times / week.
  • In case of pernicious anemia :

– Treatment d & rsquo; attack with 1000 gg lives B12 / day for 1 Oj.
– Treatment d & rsquo; interview 1 Amp lives B12 IM every month, for life.
– Any discontinuation of treatment causes a relapse of the & rsquo; anemia and & rsquo; worsening neurological disorders.
– The gastroscopy should be done each 2 years due to the risk of cancer.

  • En cas de totale gastrectomie, Treatment is the same as when pernicious anemia.


  • The megaloblastic anemias are in most cases due to a deficiency of factors antipericieux
  • Folic acid deficiency occurs in-pregnancy and postpartum,
  • that the lives B12 is due to malabsorption which must investigate the cause.
1. BLOOD SMEAR : Polynuclear hyper segmented, net polychromatophilia, anisocytose, poikylocytose, giant platelets. 2. MYELOGRAMME : Megaloblasts with asynchrony nucleocytoplasmic maturation,myelocytes and metamyelocytes large.

Dr D's course. LAMARA – Faculty of Constantine