PA H2 | Approach to Anemia & Lab Investigation — Glossary

A normocytic (or mildly microcytic) anaemia caused by chronic inflammation (infection, malignancy, autoimmune disease). IL-6 elevates hepcidin → ferroportin degraded → iron trapped in macrophages → unavailable for erythropoiesis. Iron stores are ADEQUATE but inaccessible. Distinguished from IDA by: ↑ ferritin (not ↓), ↓ or normal TIBC, ↓ TIBC (not ↑).

The gold-standard method for haemoglobin measurement. Blood is diluted in Drabkin's reagent (potassium ferricyanide + potassium cyanide), converting all haemoglobin forms to cyanmethemoglobin, which is read at 540 nm on a spectrophotometer. CV <1%, internationally standardised by ICSH.

A peripheral blood smear showing two distinct populations of red cells (e.g., microcytic + macrocytic), typically seen in mixed nutritional deficiency (IDA + B12/folate). The MCV may appear falsely normal while the RDW is elevated.

The haem precursor (protoporphyrin IX) that accumulates in developing red cells when iron is unavailable for the final synthesis step (ferrochelatase reaction). Elevated FEP indicates iron-restricted erythropoiesis — rises before anaemia develops, in Stage 2 of iron deficiency.

Haemoglobin and PCV reflect concentration, not absolute RBC mass. Haemoconcentration (dehydration, tourniquet too long) falsely elevates Hb. Dilutional pseudoanaemia (pregnancy, IV fluid loading, splenomegaly) falsely lowers Hb despite normal total RBC mass. Always interpret Hb against clinical volume status.

The liver-derived master hormone of iron homeostasis. It degrades ferroportin (the only iron-export protein), blocking iron release from enterocytes and macrophages. Hepcidin rises with iron overload and inflammation (IL-6 pathway); falls with iron deficiency and increased erythropoietic demand. Elevated hepcidin is the molecular cause of anaemia of chronic disease.

Anaemia in which the bone marrow is responding briskly to RBC loss or destruction, reflected by an RPI >2. Occurs in haemolytic anaemia and recovery from acute haemorrhage.

Neutrophils with five or more nuclear lobes (normal ≤4 lobes). A key peripheral smear finding in megaloblastic anaemia (B12 or folate deficiency), where impaired DNA synthesis delays nuclear division while the cytoplasm continues to grow.

Anaemia caused by the bone marrow failing to produce enough red cells, reflected by an RPI <2. Causes include nutritional deficiencies (iron, B12, folate), EPO deficiency (chronic kidney disease), aplastic anaemia, and anaemia of chronic disease.

Spoon-shaped (concave) nails caused by chronic iron deficiency. Iron is required for normal nail plate synthesis; depletion produces brittle, thinned nails that deform outward. A specific clinical sign pointing to IDA as the cause of anaemia.

The triad of epithelial changes seen in chronic IDA. Angular cheilitis = cracking and erythema at the corners of the mouth; atrophic glossitis = smooth, red tongue with loss of papillae. All reflect the failure of rapidly dividing epithelial cells that require iron.

The average volume of a red blood cell, measured in femtolitres (fL). Normal range: 80–100 fL. The single most important first branch point in anaemia classification: <80 fL = microcytic; 80–100 fL = normocytic; >100 fL = macrocytic.

A craving for non-nutritive substances — most specifically pagophagia (ice craving), which is highly specific for iron deficiency anaemia. Other forms include craving for clay, dirt, or chalk.

A CBC parameter measuring the variation in red cell size (anisocytosis). Normal range: 11.5–14.5%. Elevated RDW with a normal MCV suggests early or mixed nutritional deficiency — the MCV averages out two populations of cells while the RDW reveals the heterogeneity.

A corrected reticulocyte count that adjusts for both the reduced denominator (fewer total RBCs in anaemia) and early release of immature reticulocytes. RPI <2 = hypoproliferative (production failure: IDA, B12, aplastic, renal); RPI >2 = hyperproliferative (hemolysis or acute blood loss). Formula: [Retic% × (patient Hb/normal Hb)] ÷ maturation factor.

An older, less accurate visual method for haemoglobin estimation. Blood is mixed with dilute HCl to form acid haematin (brown colour), then diluted with water until it matches a standard comparator. Still used in resource-limited settings but prone to subjective error.

Fragmented red cell 'helmet cells' or 'bite cells' seen on peripheral smear when RBCs are mechanically sheared (microangiopathic haemolytic anaemia). Their presence in a smear is a diagnostic emergency — it mandates urgent investigation for TTP, HUS, or DIC.

The best single laboratory test for body iron stores — but only in the absence of inflammation. Ferritin is an acute-phase reactant: it rises with infection, malignancy, liver disease, and rheumatoid arthritis, potentially masking iron deficiency. Low ferritin (<15 ng/mL) is the earliest and most specific marker of iron store depletion.

A fragment of the cell-surface transferrin receptor (TfR1) cleaved into plasma when erythroblasts upregulate TfR1 in iron-starved erythropoiesis. Unlike ferritin, sTfR is NOT an acute-phase reactant — it remains elevated in IDA even when coexisting inflammation makes ferritin uninterpretable.

The maximum amount of iron that plasma transferrin can carry, measured in µg/dL (normal 240–450 µg/dL). TIBC rises in iron deficiency (liver makes more transferrin to capture more iron) and falls in anaemia of chronic disease (transferrin synthesis suppressed by inflammation). TIBC ≈ a proxy for total plasma transferrin.

The plasma protein that transports iron in the bloodstream. Synthesised by the liver; its synthesis increases when iron stores are low (inverse relationship with ferritin). Each molecule has two iron-binding sites. Measured indirectly as TIBC.

The percentage of transferrin's iron-binding sites occupied by iron: serum iron ÷ TIBC × 100. Normal 20–50%. Low (<15%) in IDA; low (<20%) in ACD; very high (>70%) in iron overload states. The key distinguishing parameter between IDA and ACD.