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MEGALOBLASTICANEMIAS

Dr. Sabir

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MARROW FAILURE

• Metabolically highly active, 2º to rapid cell turnover– White cell life span 12-24 hours– Platelet life span 7 days– Red blood cell lifespan 120 days

• Any slowing of DNA production marrow failure

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MEGALOBLASTIC ANEMIA

• Hemoglobin production probably normal

• Defect in nuclear replication & division

• Affects all marrow elements

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MEGALOBLASTIC ANEMIA

• Trademark cell: Oval macrocyte, (MCV > 100 fl)

• Hypersegmented neutrophils - 98%

• Pancytopenia, esp if anemia severe

• Reticulocytopenia

• LDH elevated (90%)

• Serum Fe normal or elevated

• Serum B12 or folate low

• Marrow classic megaloblastic changes

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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 proximal

jejunum

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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, ileal resection, Crohn’s

disease)

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 utilisation

Drugs: PAS, Neomycin, Colchicine, Nitrous oxide

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MEGALOBLASTIC ANEMIAS- Causes of Folic acid deficiency1. Inadequate intake

- diet lacking fresh food; chronic alcoholism, total parenteral nutrition,

2. Malabsorption

- small bowel disease (tropical sprue, celiac disease,)

- alcoholism

3. Increased requirements:

- pregnancy and lactation

- infancy

- chronic hemolysis

- malignancy

- hemodialysis

4. Defective utilisation

Drugs: folate antagonists (methotrexate, trimethoprim), purine analogues (azathioprine), pyrimidine analogues (zidovudine), RNA reductase inhibitor (hydroxyurea), miscellaneous (phenytoin)

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MEGALOBLASTIC ANEMIAS clinical features

1. Symptoms of anemia

2. Symptoms associated with vit. B12 or Folic acid deficiency

• neurologic manifestations (exclusively in vit. B12 deficiency)

- megaloblastic madness or psychosis,

- subacute, combined degeneration of the spinal cord

( proprioceptive and vibratory sensation, spinal ataxia)

• gastrointestinal complaints (vit.B12 and folic acid deficiency)

- loss of appetite

- glossitis (red, sore, smooth tongue)

- diarrhea or constipation

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• Combined degeneration refers to the combined

• demyelination of both pyramidal (lateral

• columns) and posterior (dorsal) columns, the

• signs and symptoms being predominantly in the legs

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Clinical features of SCD

• Sensory peripheral neuropathy with numbness and paraesthesia in the feet are the usual presenting symptoms. Less commonly, the disease presents as a spastic paraparesis. The signs are of:• posterior column (loss of vibration and position senses, with

positive Romberg);• upper motor neuron lesion (weakness, hypertonia and

hyperreflexia, with absent abdominal reflexes and upgoing toes); • peripheral neuropathy (absence of all jerks), reduced touch sense

and deep tenderness in the calves

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MEGALOBLASTIC ANEMIAS Diagnosis(1)

1. Blood cell count:

• macrocytic anemia ( MCV>100fl )

• 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 abnormally large with nuclear- cytoplasmic asynchrony)

• myeloid cell changes (giant bands and metamyelocytes , hypertsegmentation)

• megakariocytes are decreased and show abnormal morphology

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MEGALOBLASTIC ANEMIAS Diagnosis

1. Diagnosis of 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

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PERNICIOUS ANEMIADIAGNOSIS

1. Establishing vit.B12 deficiency anemia

2. Absence of [H+] secretion (achlorhydria) with maximal histamine stimulation

3. Radiolabeled vit. B12 absorption test (Schilling 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

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SCHILLING TEST

Cause of Cobalamin Deficiency

Part I Without IF

Part II With IF

Part III After Ab

Pernicious Anemia

Low Normal Not needed

Bacterial Overgrowth

Low Low Normal

Ileal dysfunction

Low Low Low

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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

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MEGALOBLASTIC ANEMIAS TREATMENT(1)

PERNICIOUS ANEMIA

1. Vitamin B12 im 1000 μg 3 times/week for 2 weeks, then 1000μg every 3 months (without neurological involvement)

With neurological signs: 1000µg on alternate days until no further improvement, then 1000µg every 2 months

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, as it may fall, for which iron is indicated

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MEGALOBLASTIC ANEMIAS TREATMENT(2)

FOLIC ACID DEF. ANEMIA

1. Oral folic acid 5mg/ day, for 3 months

2. Reticulocytosis after 5-7 days

3. Correction of anemia is over after 1-2 months

4. Maintenance therapy if necessary