Ecuador
Carlos Andrade Marín
Hospital

Megaloblastic Anemia
Juan Carlos Ayala Sandoval
2013
COBALAMIN
• 5-deoxyadenosylcobalamin (ado)
CoA Methyl-manolilmutasa
• Methylcobalamin
Methionine-synthase
• Hydroxocobalam...
Food source and requirements

Western Food: 5-30pg/día
Elimination: 1-3 pg/día
Body Reserves: 2-3 mg
Absorption
Transport
Transcobalamin I
(TC I)

Neutrophil granules
2/3 Saturated with cobalamin
Glycoprotein receptors
Cobalamin analo...
FOLATE
Folic Acid

Folate precursor compound

Reduced to DHF or THF
Containing one carbon unit
Folate polyglutamates

N...
Absorption
Upper small intestine
5-MethylTHF in intestinal mucosa
Monoglutamate traveling by active transport
> 400 Folic ...
Transport
• 1/3 Albumin
• 2/3 Free
• Body fluids: 5-MTHF monoglutamate
• Folate receptor high affinity
• Folate membrane t...
CLINICAL FEATURES
General tissue effects of cobalamin and
folate deficiences

Ephitelial surfaces

Complications of Pregnancy

Neural tube d...
General tissue effects of cobalamin and
folate deficiences

Cardiovascular disease

Malignacy

Neurologyc and Psychiatric ...
HEMATOLOGIC FINDINGS
Peripheral blood
• MCV > 100 fl
• Neutrophils hypersegmented
• Leukopenia > 1.5x109/L
• Platelets < 4...
HEMATOLOGIC FINDINGS
Chromosomes
• Ramdom breaks
• Reduced contraction
• Spreading of the centromere
• Overprominent satel...
CAUSES OF COBALAMIN DEFICIENCY
Inadequate Dietary Intake
•
•
•
•
•

Adults
Infants
Pernicious Anemia
Gastric Biopsy
Serum ...
DIAGNOSIS OF COBALAMIN
DEFICIENCIES

Intestinal Causes of
Cobalamin
Malabsorption

• Intestinal Stagnant Loop Syndrome
• I...
CAUSES OF FOLATE DEFICIENCY
Nutritional

Malabsorption
Excess Utilization or Loss
• Pregnancy
• Prematurity
• Hematologic ...
DIAGNOSIS OF COBALAMIN
DEFICIENCES
Serum
ELISA

Cobalamin

160-200 ng/L to 1000 ng/L

100 and 200 ng/L are regarded as bor...
DIAGNOSIS OF FOLATE DEFICIENCES
Serum
Folate

ELISA
2pg/L - 15pg/L
Serum folate rises in severe cobalamin deficiency
Intes...
TREATMENT – MEGALOBLASTIC ANEMIA

Platelets > 800 X109 /L
TREATMENT OF COBALAMIN
DEFICIENCY
Borderline cobalamin levels
Hydroxocobalamin

Cyanocobalamin

Malabsorption of cobalamin...
Hydorxocobalamin
• Replenishment of body stores
Six 1000 µg IM/3-7 days
• Maintenance therapy
1000 µg IM / month for 3 mon...
TREATMENT OF FOLATE DEFICIENCY
5-15 mg

It is a customary ton continue therapy for -4 months

Cobalamin deficiency must be...
FOLINIC ACID
• Stable form of fully reduced folate
• Toxic efects of
• Methotrexate
• DHF reductasa inhibitors
PROPHYLACTIC FOLIC ACID
Chronic dialysis

Pregnancy

Parenteral feeds

• 400 µg daily
• 5 mg daily (previous fetus with a
...
Anemia megaloblástica
Anemia megaloblástica
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Anemia megaloblástica

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Transcript of "Anemia megaloblástica"

  1. 1. Ecuador Carlos Andrade Marín Hospital Megaloblastic Anemia Juan Carlos Ayala Sandoval 2013
  2. 2. COBALAMIN • 5-deoxyadenosylcobalamin (ado) CoA Methyl-manolilmutasa • Methylcobalamin Methionine-synthase • Hydroxocobalamin
  3. 3. Food source and requirements Western Food: 5-30pg/día Elimination: 1-3 pg/día Body Reserves: 2-3 mg
  4. 4. Absorption
  5. 5. Transport Transcobalamin I (TC I) Neutrophil granules 2/3 Saturated with cobalamin Glycoprotein receptors Cobalamin analogues Transcobalamin II (TC II) Hepatic synthesis 20-60 ng / L plasma controlled by a receptor endocytosis
  6. 6. FOLATE Folic Acid Folate precursor compound Reduced to DHF or THF Containing one carbon unit Folate polyglutamates Nutritional content: >100 pg/100 g Western Food: 250 pg/día Daily requirements: 100 pg Body Reserves: 10 mg
  7. 7. Absorption Upper small intestine 5-MethylTHF in intestinal mucosa Monoglutamate traveling by active transport > 400 Folic acid < 400: 5-MTHF Bile: 60-90 pg
  8. 8. Transport • 1/3 Albumin • 2/3 Free • Body fluids: 5-MTHF monoglutamate • Folate receptor high affinity • Folate membrane transporter
  9. 9. CLINICAL FEATURES
  10. 10. General tissue effects of cobalamin and folate deficiences Ephitelial surfaces Complications of Pregnancy Neural tube defects • Macrocytosis • Multinucleated cells increased • Infertility • Prematurity • Abortion • • • • Anencephaly Myelo meningioma Encephalocele Spina bifida
  11. 11. General tissue effects of cobalamin and folate deficiences Cardiovascular disease Malignacy Neurologyc and Psychiatric manifestations •Homocystinuria > 100 pmol/L •Vascular injury •ALL •Polymorphism MTHFR 677 •Polymorphism MTHFR A1298C •Colorectal cancer •Posterior and piramidal tracts of the spinal cord •paresthesias •muscle weakness •dementia •psychosis •visual disturbances
  12. 12. HEMATOLOGIC FINDINGS Peripheral blood • MCV > 100 fl • Neutrophils hypersegmented • Leukopenia > 1.5x109/L • Platelets < 40 x109/L Bone marrow • Hypercellular marrow • Accumulation primitive cells • Giant and abnormally shaped metamyelocytes • Enlarged hyperpolyploid megakaryocytes
  13. 13. HEMATOLOGIC FINDINGS Chromosomes • Ramdom breaks • Reduced contraction • Spreading of the centromere • Overprominent satellites Ineffective hematopoiesis • Unconjugated bilirrubin in plasma • Raised urine urobilinogen • Reduced aptoglobins • Positive urine hemosiderine
  14. 14. CAUSES OF COBALAMIN DEFICIENCY Inadequate Dietary Intake • • • • • Adults Infants Pernicious Anemia Gastric Biopsy Serum antibodies Juvenil pernicious anemia Congenital Intrinsic Factor Deficiency or Funtional Abnormality Gastrectomy Food Cobalamin Malabsorption
  15. 15. DIAGNOSIS OF COBALAMIN DEFICIENCIES Intestinal Causes of Cobalamin Malabsorption • Intestinal Stagnant Loop Syndrome • Ileal resection • Selective Malabsorption of Cobalamin with Proteinuria • Tropical Sprue • Fish Tapeworn Infestation • Gluten-Induced Enteropathy • Severe Chronic Pancreatitis • HIV infection • Zollinger-Ellison Syndrome • Radiotherapy • Graft-versus-Host Disease • Drugs
  16. 16. CAUSES OF FOLATE DEFICIENCY Nutritional Malabsorption Excess Utilization or Loss • Pregnancy • Prematurity • Hematologic Disorders • Inflamatory Conditions • Homocystinuria • Long-tern Dialysis • Congestive Heart Failure, Liver Disease Antifolate Drougs Congenital Abnormalities of Folate Metabolism
  17. 17. DIAGNOSIS OF COBALAMIN DEFICIENCES Serum ELISA Cobalamin 160-200 ng/L to 1000 ng/L 100 and 200 ng/L are regarded as borderline Serum Methyl manolate and Homocysteine The serum MMA level is raised (Patients with cobalamin deficiency sufficient to cause anemia or neuropathy) Serum MMA levels fluctuate in renal failure 30% Healthy volunters (350 ng/L) 15% Elderly subjects (>350 ng/L) Serum Homocysteine (Cobalamin and Folate deficiency) Cobalamin Abosrption Urinary excretion test Patient is fasted ivernight Cyanocobalamin oral Radiactive Cyanocobalamin or Hydroxocobalamin (1mg) 24-hour urine specimen After 48 hours with IF
  18. 18. DIAGNOSIS OF FOLATE DEFICIENCES Serum Folate ELISA 2pg/L - 15pg/L Serum folate rises in severe cobalamin deficiency Intestinal stagnant loop syndrome Red Cell Folate Less afected tan the serum assay by recent diet 160 – 640 pg/L False normal results
  19. 19. TREATMENT – MEGALOBLASTIC ANEMIA Platelets > 800 X109 /L
  20. 20. TREATMENT OF COBALAMIN DEFICIENCY Borderline cobalamin levels Hydroxocobalamin Cyanocobalamin Malabsorption of cobalamin Rises in serum MMA levels Indications for starting cobalamin therapy • Well-documented megaloblastic anemia • Hematologic abnormality • Neuropathy due to the deficiency Total gastrectomy or Ileal recection Patients who have undergone gastric reduction for control of obesity Reciving long-term treatment with proton pump inhibitors
  21. 21. Hydorxocobalamin • Replenishment of body stores Six 1000 µg IM/3-7 days • Maintenance therapy 1000 µg IM / month for 3 months Cyanocobalamin (Poorer retention) Small fraction of cobalamin can be absorbed passively through mucous membranes Large daily oral doses can be used in PA Sublingual therapy Oral therapy: Important to monitor compliance 2000 pg
  22. 22. TREATMENT OF FOLATE DEFICIENCY 5-15 mg It is a customary ton continue therapy for -4 months Cobalamin deficiency must be excluded USA: Food fortification with folic acid Long-term folic acid therapy • Deficiency cannot be corrected • Gluten-Inuduced enteropathy • Important to measure the serum cobalamin
  23. 23. FOLINIC ACID • Stable form of fully reduced folate • Toxic efects of • Methotrexate • DHF reductasa inhibitors
  24. 24. PROPHYLACTIC FOLIC ACID Chronic dialysis Pregnancy Parenteral feeds • 400 µg daily • 5 mg daily (previous fetus with a neural tuve defects) Reduce homocysteine levels Cognitive function in the elderly Infancy and Childhood • Smallest premature babies (first 6 weeks of life) • Folic acid 1mg daily (< 1500 g) • Normal premature babies
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