PA H5 | Hemolytic Anemias — Glossary

Jaundice due to excess unconjugated (water-insoluble) bilirubin, characterised by yellow skin/sclera but normal urine colour and normal stool colour; the typical jaundice pattern of pre-hepatic (haemolytic) causes.

A metalloprotease that cleaves ultra-large von Willebrand factor multimers; deficiency (inherited or acquired autoantibody) leads to TTP.

A sudden, transient cessation of red cell production, most commonly caused by parvovirus B19 infection of erythroid progenitor cells; clinically most severe in patients with compensated haemolytic anaemias who depend on high reticulocyte output to maintain haemoglobin.

Progressive fibrosis and infarction of the spleen from repeated vaso-occlusion in SCD, resulting in a non-functional splenic remnant and susceptibility to encapsulated organisms.

Granular blue dots within RBCs on Romanowsky stain, representing aggregated ribosomal RNA; prominent in thalassaemia and lead poisoning.

A red cell with a semicircular 'bite' on one side, created when the spleen removes a Heinz body (denatured haemoglobin precipitate) — seen in oxidative haemolysis (G6PD deficiency).

RBC from which a Heinz body has been physically removed by the spleen, leaving a 'bitten' concavity; characteristic of G6PD deficiency during oxidative crisis.

Pigment gallstones formed by precipitation of calcium salts of unconjugated bilirubin in bile supersaturated with bilirubin; found in 30–60% of patients with chronic hereditary haemolytic anaemias, particularly hereditary spherocytosis and sickle-cell disease.

GPI-anchored decay-accelerating factor on red cells that breaks down C3/C5 convertases; absent in PNH, allowing uncontrolled complement activation.

GPI-anchored membrane inhibitor of reactive lysis that blocks C5b-9 (membrane attack complex) assembly; absent in PNH.

An IgM autoantibody that binds red cell surface antigens (typically I/i) at low temperatures, causing agglutination and complement activation; titre >1:64 at 4°C considered significant.

Autoimmune haemolytic anaemia mediated by IgM cold agglutinins that bind red cells at low temperatures, activate complement, and cause predominantly hepatic extravascular haemolysis.

A state of accelerated red cell destruction in which the bone marrow increases erythropoiesis sufficiently to maintain a normal or near-normal haemoglobin; clinically marked by reticulocytosis, mild jaundice, and splenomegaly without overt anaemia.

Painful swelling of the small bones of the hands and feet in infants with SCD due to vaso-occlusion and bone infarction; often the first manifestation of the disease.

Disseminated intravascular coagulation — widespread pathological activation of coagulation, consuming clotting factors and platelets; fibrin deposition causes MAHA alongside bleeding diathesis.

A test that detects antibodies or complement (C3d) already bound to circulating red cells, using anti-human globulin reagent to cause agglutination.

A haemolytic mechanism arising from the red cell's environment — antibodies, complement, mechanical forces, toxins, or infectious agents — that destroys intrinsically normal red cells. Usually acquired.

Red cell destruction occurring within the mononuclear phagocyte system (spleen, liver, bone marrow macrophages), where opsonised or morphologically abnormal cells are recognised and phagocytosed. Accounts for ~80–85% of all haemolysis.

X-linked deficiency of glucose-6-phosphate dehydrogenase, the enzyme protecting RBCs from oxidative damage; episodic intravascular haemolysis triggered by oxidant drugs, infections, or fava beans.

Definitive test for haemoglobinopathies; separates haemoglobin variants by charge (electrophoresis) or chromatographic affinity (HPLC) to quantify HbA, HbA2, HbF, HbS, and other variants.

Free haemoglobin in urine, occurring when plasma haemoglobin concentration exceeds the renal tubular reabsorption threshold (~130–140 mg/dL) after saturation of haptoglobin; produces red-brown urine with a positive dipstick for 'blood' but no red cells on microscopy.

Premature destruction of red blood cells before the end of their normal 120-day lifespan, occurring either within blood vessels (intravascular) or within macrophages of the spleen, liver, and bone marrow (extravascular).

Anaemia resulting when the rate of red cell destruction exceeds the maximum compensatory capacity of the bone marrow, leading to a fall in haemoglobin.

Haemosiderin (iron-laden ferritin) in urinary tubular cells — a sign of chronic intravascular haemolysis; detected by Prussian blue stain on urine deposit.

Pathological iron overload caused by repeated red cell transfusions in thalassaemia major; damages heart, liver, and endocrine organs.

A legacy diagnostic test for paroxysmal nocturnal haemoglobinuria (PNH) in which patient red cells are lysed by acidified serum; now replaced by flow cytometric analysis for CD55 and CD59 surface proteins.

A plasma glycoprotein that binds free haemoglobin 1:1; the complex is cleared rapidly by hepatocytes, preventing free Hb-mediated renal and vascular toxicity. Serum haptoglobin falls in haemolysis and is a sensitive marker of red cell destruction, especially intravascular.

Minor adult haemoglobin (α2δ2) comprising 2–3.5 % of total Hb normally; elevated above 3.5 % is the hallmark of β-thalassaemia trait.

α-Thalassaemia caused by deletion of 3 of 4 α-globin alleles; excess β-chains form HbH (β4) tetramers that are unstable, causing moderately severe haemolytic anaemia.

Aggregation of deoxygenated HbS molecules into rigid tactoid fibres driven by β6 Val hydrophobic bonding; the primary molecular event in sickling.

Precipitate of denatured oxidised haemoglobin within RBCs, visible only with supravital stains (crystal violet); hallmark of G6PD deficiency during haemolytic crisis.

Autosomal dominant RBC membrane disorder due to spectrin/ankyrin defects; produces microspherocytes with increased osmotic fragility and Coombs-negative extravascular haemolysis.

Small dark-staining nuclear remnant within circulating erythrocytes, seen when the spleen's 'pitting' function is absent (splenectomy, autosplenectomy).

Haemolytic uraemic syndrome — Shiga toxin (from STEC O157:H7) injures renal glomerular endothelium, causing MAHA + thrombocytopenia + acute kidney injury; predominantly affects children.

Detects free antibody in the patient's serum by incubating with test red cells; used for cross-matching and antibody screening, not primary haemolysis diagnosis.

Intramedullary destruction of erythroblasts before their release, as occurs in β-thalassaemia due to α-chain inclusion body formation; the dominant haemolytic mechanism in thalassaemia major.

A haemolytic mechanism intrinsic to the red cell itself — a defect in membrane proteins, enzymes, or haemoglobin structure that reduces the cell's lifespan. Usually hereditary (except PNH).

Red cell lysis occurring directly within the circulation, releasing free haemoglobin into plasma; characterised by haemoglobinaemia, haemoglobinuria, and marked haptoglobin depletion.

Erythrocyte that retains the sickle shape even when reoxygenated due to cumulative membrane oxidative damage from repeated sickling cycles.

An intracellular enzyme released into plasma upon cell lysis; elevated in haemolysis (predominantly LDH-1 and LDH-2 isoforms from red cells), though non-specific. Very high levels (>10× normal) suggest intravascular haemolysis or extensive tissue destruction.

An intracellular enzyme released from lysed red cells; elevated in haemolysis, but non-specific (also elevated in myocardial infarction, hepatitis, malignancy).

Microangiopathic haemolytic anaemia — mechanical fragmentation of red cells by intravascular fibrin strands, platelet microthrombi, or turbulent flow; characterised by schistocytes and negative DAT.

Rare self-limited intravascular haemolysis caused by repetitive mechanical trauma (prolonged marching, drumming) rupturing red cells in small vessels of the feet or hands.

The network of macrophages in the spleen (red pulp), liver (Kupffer cells), bone marrow, and lymph nodes responsible for recognising and destroying senescent or opsonised red cells; the primary site of extravascular haemolysis.

X-linked gene encoding phosphatidylinositol glycan class A — essential for biosynthesis of GPI anchors; somatic mutation causes PNH.

Paroxysmal nocturnal haemoglobinuria — acquired somatic PIG-A mutation causes GPI-anchor deficiency, loss of CD55 and CD59, and complement-mediated intravascular haemolysis.

Blue-grey staining of enlarged red cells on Romanowsky-stained peripheral smear, reflecting residual ribosomal RNA in newly released reticulocytes; correlates with reticulocytosis and indicates active erythropoietic response.

Clumping of red cells on smear caused by IgM cold agglutinins cross-linking adjacent cells, seen in cold AIHA; causes spuriously elevated MCV on automated analysers.

The percentage (or absolute number) of immature red cells newly released from the bone marrow, identified by residual ribosomal RNA. Elevated reticulocyte count is the primary marker of compensatory erythropoiesis in haemolysis.

A corrected measure of reticulocyte count that adjusts for the degree of anaemia and early reticulocyte release; RPI >3 indicates hyperproliferative response (haemolysis or haemorrhage), RPI <2 indicates hypoproliferative anaemia.

A red cell fragment produced by mechanical shearing of erythrocytes by fibrin strands in microvasculature (microangiopathic haemolytic anaemia) or prosthetic surfaces; helmet-shaped or triangular. The hallmark peripheral smear finding of MAHA.

Autosomal recessive haemoglobinopathy caused by homozygous HbS (β6 Glu→Val), characterised by deoxygenation-triggered HbS polymerisation, vaso-occlusive crises, and chronic haemolytic anaemia.

Heterozygous carrier state with approximately 40 % HbS and 60 % HbA; clinically silent under normal conditions.

Screening test for HbS: sodium metabisulphite deoxygenates the sample causing turbidity if HbS is present; does NOT distinguish sickle cell disease from sickle cell trait.

A round red cell with no central pallor and reduced surface-to-volume ratio, resulting from membrane loss (via antibody-coated membrane phagocytosis in AIHA or genetic spectrin/ankyrin defects in hereditary spherocytosis). Has reduced osmotic resistance.

RBC with a dense central Hb spot, peripheral pale zone, and dense rim; formed when membrane surface area is disproportionately large relative to Hb content; seen in SCD, thalassaemia, liver disease.

Group of inherited disorders characterised by quantitative reduction or absence of structurally normal globin chain synthesis, leading to imbalance of α and β chains and ineffective erythropoiesis.

Thrombotic thrombocytopenic purpura — acquired deficiency of ADAMTS13 leading to ultra-large vWF multimers, spontaneous platelet microthrombi, MAHA, thrombocytopenia, and organ dysfunction.

The water-insoluble form of bilirubin produced by haem catabolism in macrophages; transported bound to albumin in plasma, not excreted in urine (hence 'acholuric jaundice'). Elevated in haemolysis due to increased haem degradation.

Iron-containing granules (ferritin/haemosiderin) deposited in renal tubular epithelial cells after chronic absorption of filtered haemoglobin, shed into urine. Detected by Prussian blue stain of urine sediment; appears 2–3 days after onset of chronic intravascular haemolysis.

Obstruction of small blood vessels by rigid, adhesive sickled erythrocytes, causing ischaemia and the painful crises of sickle cell disease.

Autoimmune haemolytic anaemia mediated by IgG antibodies that bind red cell antigens optimally at 37°C, causing extravascular destruction in the spleen.

Homozygous β0 or severe β+ thalassaemia; transfusion-dependent severe anaemia presenting in the first year of life with massive organomegaly and skeletal changes.

Heterozygous β-thalassaemia; produces mild microcytic anaemia with elevated HbA2 (>3.5 %), the key discriminator from iron deficiency anaemia.