PA H3 | Microcytic Anemias — Glossary

Variation in red cell size, quantified by the RDW on CBC. Elevated RDW (>14.5%) is the earliest CBC change in iron deficiency, preceding the fall in MCV. Also elevated in B12/folate deficiency, mixed deficiency, and after transfusion of mixed-age cells.

Combined variation in red cell size (anisocytosis) and shape (poikilocytosis), characterised on peripheral smear in iron deficiency anaemia and other haemoglobinopathies. Anisocytosis correlates with elevated RDW; poikilocytosis describes the variety of abnormal forms (pencil cells, target cells, teardrop cells).

A hormone secreted by erythroblasts in response to EPO stimulation (after haemorrhage or haemolysis) that suppresses hepcidin production, rapidly liberating stored iron for erythropoiesis. Pathologically overactive in β-thalassaemia major — the massive erythropoietic drive suppresses hepcidin → excessive iron absorption → iron overload even without transfusion.

The principal intracellular iron storage protein — a hollow protein shell (24 subunits) that can hold up to 4,500 Fe³⁺ atoms. Found in hepatocytes, macrophages, and enterocytes. Serum ferritin reflects total body iron stores (1 ng/mL ≈ 8 mg of stored iron), but it is an acute-phase reactant and rises with inflammation regardless of iron status.

The only known iron-export protein in the body. Located on the basolateral surface of duodenal enterocytes, splenic macrophages, and hepatocytes, it exports iron into the portal blood and plasma. Hepcidin binds ferroportin and targets it for degradation, blocking iron release.

The trio of molecular transporters governing duodenal iron absorption. Dcytb (duodenal cytochrome b) is a brush-border ferrireductase that reduces Fe³⁺ → Fe²⁺. DMT1 (Divalent Metal Transporter 1) transports Fe²⁺ into the enterocyte from the lumen. Ferroportin exports iron from the basolateral side into portal blood.

A laboratory technique that separates haemoglobin variants by their electrical charge on cellulose acetate (alkaline) or citrate agar (acid) gels. Used to identify HbS, HbC, HbE, HbD, and to quantify HbA2 and HbF. Now largely superseded by HPLC for diagnostic accuracy, but remains in use for variant confirmation.

A minor adult haemoglobin tetramer comprising two α-globin and two δ-globin chains (α₂δ₂). Normal level <3.5%. Elevated HbA2 (>3.5%) is the diagnostic hallmark of β-thalassaemia trait, measured by HPLC or Hb electrophoresis.

A structural haemoglobin variant caused by a point mutation in the β-globin gene (Glu26Lys) common in Southeast Asia and northeastern India. Alone it causes mild microcytosis; HbE/β-thalassaemia compound heterozygosity causes a clinical syndrome ranging from thalassaemia intermedia to major severity.

Haemoglobin comprising two α-globin and two γ-globin chains (α₂γ₂). The dominant haemoglobin in fetal life; normally <1% in adults. Compensatorily elevated in β-thalassaemia major and intermedia, sickle cell disease, and hereditary persistence of fetal haemoglobin (HPFH).

An insoluble aggregate of degraded ferritin plus iron that accumulates when iron overload overwhelms ferritin capacity. Visible as golden-brown granules on H&E; confirmed by Perls' Prussian Blue stain (iron + potassium ferrocyanide → bright blue granules). Less readily mobilised than ferritin.

A 25-amino-acid peptide hormone secreted by hepatocytes that degrades ferroportin, blocking iron export from enterocytes and macrophages. The master regulator of iron homeostasis: rises with iron overload and inflammation (IL-6/JAK-STAT3 pathway), falls with iron deficiency and erythropoietic demand. The molecular driver of anaemia of chronic disease.

The gold-standard method for haemoglobin variant analysis and thalassaemia diagnosis. Separates haemoglobin variants (HbA, HbA2, HbF, HbS, HbC, HbE, etc.) by charge and molecular weight. Essential for diagnosing β-thalassaemia trait (HbA2 >3.5%), HbS, HbE, and compound heterozygotes.

A state in which the bone marrow produces large numbers of erythroid precursors that die within the marrow before becoming mature RBCs (intramedullary destruction). Leads to: ↑ LDH, ↑ unconjugated bilirubin, ↑ ferritin (iron recycles from destroyed precursors), and — paradoxically — suppressed hepcidin (via erythroferrone). The dominant mechanism in β-thalassaemia major and megaloblastic anaemia.

Treatment to remove excess iron in transfusion-dependent patients (e.g., β-thalassaemia major). Agents include desferrioxamine (parenteral), deferasirox and deferiprone (oral). Targets iron deposited in myocardium, liver, and endocrine glands (the principal causes of death in transfused thalassaemia patients).

Spoon-shaped (concave) nails — a specific clinical sign of chronic iron deficiency. Iron is required for normal nail plate keratin synthesis; depletion causes brittle, thinned nails that deform outward and hold a drop of water. Reverts with iron repletion.

The average haemoglobin concentration per unit volume of red cells (normal 31–36 g/dL). Reduced (<31 g/dL) in IDA and some thalassaemias (hypochromia); elevated (>36 g/dL) exclusively in hereditary spherocytosis — a reliable distinguishing feature.

A simple CBC-derived ratio used to differentiate thalassaemia trait from IDA: MCV ÷ RBC count. <13 suggests thalassaemia trait (many small cells, high RBC count); >13 suggests IDA (fewer, smaller cells). A screening tool — not diagnostic; requires confirmation with Hb electrophoresis or HPLC.

A test of red cell membrane integrity: RBCs are placed in solutions of decreasing NaCl concentration and the percentage lysed at each concentration is measured. Hereditary spherocytosis shows increased osmotic fragility (spherocytes lyse at higher NaCl than normal cells). IDA and thalassaemia trait show decreased fragility (flat cells are more resistant to osmotic stress).

Elongated, thin, rod-shaped erythrocytes seen on peripheral smear in IDA. They form when iron-deficient, hypochromic cells flatten and elongate under membrane tension. More specific for IDA than for other microcytic anaemias such as thalassaemia trait.

A histochemical stain for iron in tissue sections and bone marrow biopsies. Iron reacts with potassium ferrocyanide to produce bright blue granules. Used to confirm hemosiderin in tissues, to assess marrow iron stores (absent in IDA), and to identify ringed sideroblasts (in sideroblastic anaemia).

The triad of: (1) iron deficiency anaemia, (2) post-cricoid dysphagia, and (3) oesophageal webs (thin mucosal folds at the cricopharyngeal junction). Occurs predominantly in middle-aged women. Carries a 10–15% risk of pharyngeal or upper oesophageal squamous cell carcinoma — making it a premalignant condition requiring follow-up and web dilation.

Abnormal erythroid precursors in which iron-laden mitochondria encircle the nucleus, forming a ring of Perls-blue granules (≥5 granules encircling ≥1/3 of the nucleus). Pathognomonic of sideroblastic anaemia. The iron is present but cannot be incorporated into haem due to mitochondrial enzyme defects.

A microcytic (or dimorphic) anaemia characterised by ringed sideroblasts in the bone marrow on Perls' stain. Caused by defects in haem biosynthesis (X-linked: ALAS2 mutations; acquired: myelodysplasia, alcohol, isoniazid, lead poisoning). Iron stores are high (not depleted) — iron is trapped in mitochondria rather than being used for haemoglobin synthesis.

Red cells with a central dense area surrounded by a pale ring and a peripheral dense rim — resembling a shooting target (or Mexican hat on edge view). Seen in IDA, thalassaemia, HbC disease, liver disease, and post-splenectomy states. Result from excess membrane relative to cell volume.

Iron depletion progresses sequentially: Stage 1 (storage depletion) — serum ferritin falls, no anaemia; Stage 2 (transport depletion / iron-deficient erythropoiesis) — serum iron falls, TIBC rises, transferrin saturation <15%, FEP rises, RDW rises, no anaemia yet; Stage 3 (IDA) — Hb falls below threshold, MCV <80 fL, full microcytic hypochromic picture.

The maximum iron that plasma transferrin can bind (normal 240–450 µg/dL). TIBC ↑ in IDA (liver makes more transferrin to capture scarce iron); TIBC ↓ or normal in anaemia of chronic disease and iron overload (transferrin synthesis suppressed).

The percentage of transferrin's iron-binding sites occupied by iron (serum iron ÷ TIBC × 100). Normal 20–50%. <15% in IDA; <20% in anaemia of chronic disease; >70% in iron overload states — at high saturation, free non-transferrin-bound iron generates hydroxyl radicals via Fenton chemistry.

A group of inherited disorders caused by deletion of one or more of the four α-globin genes (HHba). Gene dose determines severity: 1 gene deletion = silent carrier; 2 = α-thalassaemia trait (mild microcytosis); 3 = HbH disease (haemolytic anaemia); 4 = Hb Bart's hydrops fetalis (incompatible with extrauterine life). HbA2 is normal or low — electrophoresis cannot diagnose it directly.

Homozygous or compound heterozygous β-globin mutations causing severe haemolytic anaemia (Hb 2–6 g/dL) requiring regular transfusions from infancy. Marked erythroid hyperplasia → extramedullary haematopoiesis → hepatosplenomegaly, 'hair-on-end' skull X-ray, rodent facies. Complications: transfusion-related iron overload (chelation required).

Heterozygous β-globin mutation producing mild microcytic anaemia (Hb 10–13 g/dL), elevated HbA2 >3.5%, and a high RBC count. Iron studies are normal (distinguishes it from IDA). Clinically asymptomatic but critical to identify for genetic counselling — two carriers can produce a β-thalassaemia major child.