Macrocytic Anaemia

Prof. Rafi Ahmed GhoriFCPS

Professor & Chairman Medicine

Liaquat University of Medical & Health Sciences, 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 by impaired DNA synthesis

– deficiency of vitamin B12 or folic acid

Vitamin B12 Deficiency• Cobalamin.

• Exclusive source is dietary animal products.

• 2mg to 3mg per day.

• 70% is absorbed.

• Stores are 5000mg.

• Present mostly in liver, kidney and heart which is enough for several years.

Aetiology• Inadequate diet.

• Impaired absorption.

• Increased requirements.

Aetiology• Inadequate dietary intake

– Vegans.

• Impaired absorption– Stomach

• Pernicious anaemia.

• Gastrectomy.

• Congenital deficiency of intrinsic factor.

– Small bowel

– Ileal disease or resection

– Bacterial overgrowth.

– Tropical sprue.

– Fish tapeworm.

Aetiology• Abnormal metabolism

– Congenital transcobalamin II deficiency.

– Nitrous oxide (inactivates B12).

Megaloblastic Anaemia• Defective DNA synthesis and normal

RNA/protein synthesis.

• Rapidly proliferating cells are affected.

• Ineffective haematopoiesis

Clinical Features• Insidious onset.

• Progressive increase in symptoms of anaemia.

• Patient may look lemon-yellow colour.

• Mild jaundice.

• Red sore tongue (glossitis) and angular stomatitis.

Clinical Features• Neurological changes, if left untreated,

can be irreversible.

• Polyneuropathy involving peripheral nerve, posterior and lateral column of spinal cord (subacute combined degeneration).

• Patient feels symmetrical paraesthesiae in fingers and toes, loss of posterior column 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.

Diagnostic Features• Serum iron

– elevated.

• Iron-binding capacity

– increased saturation.

• Serum ferritin

– elevated.

• Plasma LDH

– elevated, often markedly.

Diagnosis of B12 Deficiency Anaemia

• Normal and high MCV, high RDW.

• Triad

– Macroovalocytes.

– Howell-Jolly bodies.

– Hypersegmented neutrophils.

Pernicious Anaemia• Lack of intrinsic factor.

• Most important and common cause of B12 deficiency.

• 90% patients have antiparietal cell antibodies – not specific.

Pernicious Anaemia• Laboratory findings

– Features of B12 deficiency.

– Auto antibodies (anti-IF, antiparietal antibodies).

– Achlorhydria.

– Positive Schilling test.

• IM injection of B12.

Schilling test• Helps determine the aetiology of

megaloblastic anaemia.

• Dietary deficiency, absence of IF or malabsorption.

• Patient is given radioactive labelled B12 orally followed within 2 hours by an IM injection of unlabeled B12.

• Urine is collected for 24 hours and the radioactivity of the urine is determined.

Schilling test• <7.5% excretion – Pernicious anaemia

and malabsorption.

• If excretion is <7.5%, oral doses of B12 and IF given.

• >7.5% excretion – Pernicious anaemia.

• <7.5% excretion – malabsorption defect.

Folate Deficiency• Same characteristics as in vitamin B12

deficiency.

• However, neurological changes seen in vitamin 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 good for 3-6 months.

Folate Deficiency• Decreased intake.

• Increased requirements.

• Malabsorption.

• Impaired utilisation.

Folate Deficiency• Laboratory findings

– Normal or high MCV, high RDW.

– Features of ineffective erythropoiesis (increased indirect bilirubin, increased LDH).

– Low serum and red cell folate.

– Increased urinary excretion of foriminoglutamic acid (FIGLU).

– Therapeutic doses of folate can partially correct B12 deficiency anaemia but no effect on neurological manifestations.

Folate Deficiency• Both serum and red cell folate levels

must be decreased to diagnose folate deficiency.

• Red cell folate is a better indication of folate stores.

• Low serum folate usually indicates an imminent folic acid deficiency and precedes red cell folate deficiency.

Folate Deficiency• Cobalamin is necessary to keep the

conjugated form of folate within the cells.

• Neither serum nor red cell folate is a good indicator of folate stores in the presence of cobalamin deficiency.

• Serum folate may be falsely increased and red cell folate falsely decreased in cobalamin deficiency.

Treatment• B12 deficiency

– Hydrocobalamin 1000-g IM (total 5-6 mg) during first-three weeks.

– Hydrocobalamin 1000-g every three months (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-g daily) for pregnant women is recommended.

Macrocytic Anaemia without Megaloblastosis

• High MCV, Normal RDW, round macrocytes, absence of hypersegmented neutrophils.

Macrocytic Anaemia without Megaloblastosis

• Alcoholism.

• Liver disease.

• Myelodysplastic syndrome.

• Hypothyroidism.

• Aplastic anaemia.

• Drugs.

Investigation of macrocytic anaemia

High MCV / MCH

Blood film

Reticulocyte count

High

Acute blood loss

Haemolytic anaemia

Normal / low

Bone marrow morphology

Non-megaloblastic

Normoblastic

Alcoholic liver disease, Hypothyroid

Dyserythropoietic

Myelodysplasia

Megaloblastic Folate and B12

Folate low

Folate deficiency

B12 low

B12 deficiency

Thanks