MEGALOBLASTIC ANEMIA

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MEGALOBLASTICANEMIA

• M. Kazmierczak XI 2012

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MEGALOBLASTIC ANEMIASCauses

• 1. Vit. B12 deficiency
• 2. Folic acid deficiency

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VITAMIN B12 AND FOLIC ACID-PHYSIOLOGIC
CONSIDERATIONS

• Vitamin B12
  Folic acid
• Sources meat, fish
  green vegetables, yeast
• Daily requirement 2-5 ug
  50-100 ug
• Body stores 3-5 mg (liver)
  10-12mg (liver)
• Places of absorption ileum
  duodenum and proxymal
• segment of small intestine
• 
  

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MEGALOBLASTIC ANEMIAS Causes of Vit.B12
deficiency(1)

• 1. Malabsorption
• a) Inadequate production of intrinsic factor
• - pernicious anemia
• - gastrectomy, partial or total
• b) Inadequate releasing vit. B12 from food
• (partial gastrectomy, abnormality of
  stomach function,
• chronic pancreatic insufficiency)
• c) Terminal ileum disease (sprue, celiac
  disease, ilea resection, Crohn
• disease, Imerslund syndrome)
• d) Competition for intestinal B12
• - bacterial overgrowth jejunal diverticula,
  intestinal stasis and
• obstruction due to strictures,
  blind-loop syndrome
• - Fish tapeworm

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MEGALOBLASTIC ANEMIAS Causes of Vit.B12
deficiency(2)

• 2. Inadequate intake
• - vegetarians
• 3. Inadequate utylisation
• Drugs PAS, Neomycin, Colchicin, Nitrous oxide

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MEGALOBLASTIC ANEMIAS- Causes of Folic acid
deficiency

• 1. Inadequate intake
• - diet lacking fresh, slightly cook food
  chronic alcoholism, total parenteral nutrition,
• 2. Malabsorption
• - small bowel disease (sprue, celiac disease,)
• - alcoholism
• 3. Increased requirements
• - pregnancy and lactation
• - infancy
• - chronic hemolysis
• - malignancy
• - hemodialysis
• 4. Defective utilisation
• Drugsfolate antagonists(methotrexate,
  trimethoprim, triamteren), purine analogs
  (azathioprine), primidine analogs (zidovudine),
  RNA reductase inhibitor (hydroxyurea),
  miscellaneous (phenytoin, N2)

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MEGALOBLASTIC ANEMIAS clinical features

• 1. Symptoms of anemia
• 2. Symptoms associated with vit. B12 or Folic
  acid deficiency
• neurologic manifestations (exclusivly in wit.
  B12 deficiency)
• - megaloblastic madness or psychosis,
• - subacute, combined degeneration of the spinal
  cord
• ( proprioceptive and vibratory sensation,
  spinal ataxia)
• gastrointestinal compraints (vit.B12 and folic
  acid deficiency)
• - loss of appetite
• - glosstis (red, sore, smooth tongue)
• - diarrhea or constipation

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MEGALOBLASTIC ANEMIAS Diagnosis(1)

• 1. Blood cell count
• macrocytic anemia ( MCVgt100fl )
• thrombocytopenia
• leucopenia (granulocytopenia)
• low reticulocyte count
• 2. Blood smear
• macroovalocytosis , anisocytosis, poikilocytosis
• hypersegmentation of granulocytes

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MEGALOBLASTIC ANEMIAS Diagnosis(2)

• 3. Laboratory features
• indirect hyperbilirubinemia
• elevation of lactate dehrogenase (LDH)
• serum iron concentration- normal or increased
• 4. Bone marrow smear
• hypercellular
• increased erythroid /myeloid ratio
• erythroid cell changes (megaloblasts, RBC
  precursor a abnormally large with nuclear-
  cytoplasmic asynchrony)
• myeloid cell changes (giant bands and
  metamyelocytes , hypersegmentation)
• megakariocytes are decreased and show abnormal
  morphology

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Megaloblastic erythropoiesis
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MEGALOBLASTIC ANEMIAS Diagnosis

• 1. Diagnosis megaloblastic anemia
• 2. Establishing a type of deficiency (vit. B12
  and/or folic acid)
• 3. Establishing a cause of deficiency

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VIT B12 DEFICIENCY ANEMIA DIAGNOSIS

• 1. Establishing megaloblastic anemia
• 2. Clinical symptoms of vit. B 12 deficiency
• 3. Low serum vit. B 12
• 4. Increased concentration of methylmalonic acid
  (MMA) and total homocysteine

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PERNICIOUS ANEMIADIAGNOSIS

• 1. Establishing vit.B12 deficiency anemia
• 2. Absence of hydrogen ion secretion
  (achlorhydria) with maximal histamine stimulation
  
• 3. Radiolabeled vit. B12 absorption test
  (Schilling urinary excretion test) very reduced
  absorption of the B12-isotope, corrected to
  normal only when coadministered with a source of
  gastric IF.
• 4. Intrinsic factor, parietal cell and IF-vit.B12
  complex antibodies
• 5. Chronic atrophic gastritis

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Atrophic glossitis
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FOLIC ACID DEFICIENCY ANEMIA DIAGNOSIS

• 1. Establishing megaloblastic anemia
• 2. History causes of folate deficiency
• 3. Absence neurologic symptoms
• 4. Low serum and red blood cell folic acid
• 5. Normal concentration of methylmalonic acid
  (MMA) and increased of total homocysteine

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MEGALOBLASTIC ANEMIAS TREATMENT(1)

• PERNICIOUS ANEMIA
• 1. Vitamin B12 administration intramuscular in
  dose 1000 (100) µg per day for a week , then 100
  µg 2x per week for 2 weeks, 1 x per week 100µg
  for month
• 2. Reticulocytosis begins 2 or 3 days after
  therapy started and maximal number reached on day
  5 to 8.
• Serum iron monitoring, after 7-10 days of
  vit.B12 treatment,
• if Fe deficiency is diagnosed we should start
  iron substitution
• 3. 100 ug vit.B12 i.m. every month, regimen that
  must be mainted for the rest on the patients
  life.
• 4. Oral substitution of cobalamin at doses
  1000-2000ug/d

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MEGALOBLASTIC ANEMIAS TREATMENT(2)

• FOLIC ACID DEFICIENCY ANEMIA
• 1. Oral administration of Ac. folicum 1 (5) mg
  per day, for
• 3 months, and maintance therapy if its
  necessary.
• 2. Reticulocytosis after 5-7 days
• 3. Correction of anemia is over after 1-2
  months
• therapy
• 4. Maintenance therapy if necessary