MacrocyticAnaemiaProf. Rafi Ahmed GhoriFCPSProfessor & Chairman MedicineLiaquat University of Medical & HealthSciences, Jamshoro
Red Cell Indices• Mean cell volume (MCV)• Mean cell Hb concentration (MCHC)• Red cell distribution width (RDW)
Mean Cell Volume(Normal 80 - 100 fL)• Low MCV = Microcytic• Normal MCV = Normocytic• High MCV = Macrocytic
Mean Cell Hemoglobin Concentration(Normal 32-36 g/dL)• Low MCHC = hypochromic• Normal MCHC = normochromic• High MCHC = hyperchromic
Decreased Production AnemiaMacrocytic• Megaloblastic anemia
Megaloblastic Anemia• Definition– anemia or pancytopenia caused byimpaired DNA synthesis– deficiency of vitamin B12 or folicacid
Vitamin B12 Deficiency• Cobalamin.• Exclusive source is dietary animalproducts.• 2mg to 3mg per day.• 70% is absorbed.• Stores are 5000mg.• Present mostly in liver, kidney and heartwhich is enough for several years.
Megaloblastic Anaemia• Defective DNA synthesis and normalRNA/protein synthesis.• Rapidly proliferating cells are affected.• Ineffective haematopoiesis
Clinical Features• Insidious onset.• Progressive increase in symptoms ofanaemia.• Patient may look lemon-yellow colour.• Mild jaundice.• Red sore tongue (glossitis) and angularstomatitis.
Clinical Features• Neurological changes, if left untreated,can be irreversible.• Polyneuropathy involving peripheralnerve, posterior and lateral column ofspinal cord (subacute combineddegeneration).• Patient feels symmetrical paraesthesiaein fingers and toes, loss of posteriorcolumn sensation.
Clinical Features• Progressive weakness and ataxia.• Paraplagia.• Dementia and optic atrophy.
Diagnostic Features• Haemoglobin– often reduced, may be very low.• Mean cell volume– usually raised, commonly > 120 fl.• Erythrocyte count– low for degree of anaemia.
Diagnostic Features• Blood film– oval macrocytosis.– poikilocytosis.– red cell fragmentation.– neutrophil hypersegmentation.• Reticulocyte count– low for degree of anaemia.• Leucocyte count– low or norma.• Platelet count– low or normal.
Diagnostic Features• Bone marrow– increased cellularity.– megaloblastic changes in erythroid series.– giant metamyelocytes.– dysplastic megakaryocytes.– increased iron in stores.– pathological non-ring sideroblasts.
Diagnosis of B12 DeficiencyAnaemia• Normal and high MCV, high RDW.• Triad– Macroovalocytes.– Howell-Jolly bodies.– Hypersegmented neutrophils.
Pernicious Anaemia• Lack of intrinsic factor.• Most important and common cause ofB12 deficiency.• 90% patients have antiparietal cellantibodies – not specific.
Pernicious Anaemia• Laboratory findings– Features of B12 deficiency.– Auto antibodies (anti-IF, antiparietalantibodies).– Achlorhydria.– Positive Schilling test.• IM injection of B12.
Schilling test• Helps determine the aetiology ofmegaloblastic anaemia.• Dietary deficiency, absence of IF ormalabsorption.• Patient is given radioactive labelled B12orally followed within 2 hours by an IMinjection of unlabeled B12.• Urine is collected for 24 hours and theradioactivity of the urine is determined.
Schilling test• <7.5% excretion – Pernicious anaemiaand malabsorption.• If excretion is <7.5%, oral doses of B12and IF given.• >7.5% excretion – Pernicious anaemia.• <7.5% excretion – malabsorption defect.
Folate Deficiency• Same characteristics as in vitamin B12deficiency.• However, neurological changes seen invitamin B12 deficiency do not occur.• Pteroylglutamic acid.• Green leafy vegetables, egg, mild, yeast,liver, micro-organisms.
Folate Deficiency• Destroyed by heat.• 200mg/day.• 50-70% absorbed from proximal ileum.• Stored in liver (5-10 mg), which is goodfor 3-6 months.
Folate Deficiency• Laboratory findings– Normal or high MCV, high RDW.– Features of ineffective erythropoiesis (increasedindirect bilirubin, increased LDH).– Low serum and red cell folate.– Increased urinary excretion of foriminoglutamicacid (FIGLU).– Therapeutic doses of folate can partially correctB12 deficiency anaemia but no effect onneurological manifestations.
Folate Deficiency• Both serum and red cell folate levelsmust be decreased to diagnose folatedeficiency.• Red cell folate is a better indication offolate stores.• Low serum folate usually indicates animminent folic acid deficiency andprecedes red cell folate deficiency.
Folate Deficiency• Cobalamin is necessary to keep theconjugated form of folate within thecells.• Neither serum nor red cell folate is agood indicator of folate stores in thepresence of cobalamin deficiency.• Serum folate may be falsely increasedand red cell folate falsely decreased incobalamin deficiency.
Treatment• B12 deficiency– Hydrocobalamin 1000-µg IM (total 5-6 mg)during first-three weeks.– Hydrocobalamin 1000-µg every threemonths (may be for lifelong).– Treat the underlying cause if possible.
Treatment• Folate deficiency– Folic acid (5-mg) daily for 4 months.– Prophylactic folic acid (400-µg daily) forpregnant women is recommended.
Macrocytic Anaemia withoutMegaloblastosis• High MCV, Normal RDW, roundmacrocytes, absence of hypersegmentedneutrophils.