I- DEFINITION :
- 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.
II- EPIDEMIOLOGY :
- 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%.
III- PHYSIOLOGICAL RECALL :
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.
IV- PATHOPHYSIOLOGY :
—> 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.
V- DIAGNOSTIC CLINIC :
A- anemic syndrome : d & rsquo; gradual installation
- Pale mucocutaneous.
- conjunctival jaundice.
- Dyspnea effort.
- 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
- Atrophic glossitis with dry mouth and burns in contact with hot and spicy food.
- A language & rsquo; depapillated first red and then smooth the edges, brilliant and totally depapillated, c & rsquo; is glossitis Hunter.
- 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
- A pyramidal syndrome (sign bilateral Babinski, hyperéflexie O-T.)
- A posterior cord syndrome (muscle cramps, paresthésie, spinal intermittent claudication.)
D- other signs :
- reversible infertility in women and asthénospermie in the & rsquo; man.
- Hyperpigmentation skin especially at the palmar region.
- moderate splenomegaly.
WE- DIAGNOSTIC PARACLINIQUE :
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.
VII- DIFFERENTIAL DIAGNOSIS :
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
VIII- ETIOLOGICAL DIAGNOSIS :
A- ANEMIA MÉGALOBLASTIOUE BY DEFICIENCY FOLATES :
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.
B- ANEMIA MÉGALOBLASTIOUE BY DEFICIENCY VIT B12 :
- Failing & rsquo; s contribution: exceptional, respect strict vegetarians.
- 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.
C- ANEMIA MÉGALOBLASTIOUE D & rsquo; ORIGIN DRUG :
- 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.
D- ANEMIA MÉGALOBLASTIOUE D & rsquo; ORIGIN NEOPLASTIC :
- 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.
IX- TREATMENT :
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.
X- CONCLUSION :
- 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.
Dr D's course. LAMARA – Faculty of Constantine