RBC Disease

Define anaemia.

A reduction in haemoglobin, red blood cells and/or haematocrit that lowers the oxygen-carrying capacity of blood and can cause tissue hypoxia.

What WHO haemoglobin thresholds define anaemia in adults

Men: Hb <130 g/L; non-pregnant women: Hb <120 g/L; pregnant women: Hb <110 g/L.

What units do UK laboratories use for haemoglobin

g/L (not g/dL). Check and convert units when using international sources.

What are common symptoms of anaemia

Fatigue, weakness, shortness of breath, palpitations/tachycardia, dizziness and sometimes paraesthesia.

What examination findings may suggest anaemia or its cause

Pallor; koilonychia with iron deficiency; jaundice with haemolysis; glossitis or angular stomatitis with B12, folate or iron deficiency.

Why can the speed of haemoglobin decline matter clinically

A rapid fall often causes tachycardia; longstanding anaemia may be compensated for, so heart rate can be normal.

Name major mechanisms or causes of anaemia.

Bone marrow failure/infiltration, iron problems, B12/folate deficiency, organ disease, blood loss, haemolysis and inherited gene mutations.

What are common causes of microcytic anaemia

Iron deficiency, thalassaemia, anaemia of chronic inflammation and sideroblastic anaemia.

What are common causes of normocytic anaemia

Acute blood loss, renal disease/chronic inflammation, many haemolytic anaemias and early mixed-deficiency states.

What are causes of macrocytic anaemia

Megaloblastic: B12 or folate deficiency. Non-megaloblastic: liver disease, alcohol excess, hypothyroidism or myelodysplasia.

How does the reticulocyte count help classify anaemia

Raised: suggests red-cell loss or destruction, such as haemorrhage or haemolysis. Normal/low: suggests reduced or ineffective production.

What are the main components of the initial laboratory work-up for anaemia

FBC and red-cell indices, peripheral blood film and reticulocyte count; then targeted tests such as ferritin, B12, folate or haemoglobinopathy screening.

What is the role of a peripheral blood film

Assess red-cell size, shape, colour and inclusions; check automated analyser results and look for evidence of wider marrow problems in white cells or platelets.

Which stain is standard for peripheral blood films in UK practice

Leishman or May–Grünwald–Giemsa (MGG), a Romanowsky stain.

What is anisocytosis

Variation in red blood cell size.

What is poikilocytosis

Variation in red blood cell shape.

What is hypochromia

Red cells take up less stain because they contain less haemoglobin; usually associated with low MCH and MCHC.

What is polychromasia

A bluish tinge on red cells caused by immature red cells (reticulocytes).

What are Howell–Jolly bodies and when may they be seen

Nuclear remnants in red cells; may occur after splenectomy or with hyposplenism.

What does basophilic stippling indicate, and what are examples of associations

Aggregates of ribosomal RNA; associated with lead poisoning and thalassaemia.

What are Pappenheimer bodies

Iron-containing granules in red cells (siderotic granules).

What are Heinz bodies

Precipitated, denatured haemoglobin; associated with G6PD deficiency and oxidative stress.

What are reticulocytes

Immature, anucleate red cells that retain residual RNA and indicate bone-marrow red-cell production.

When may bone marrow examination be indicated in anaemia

Unexplained anaemia, with or without other cytopenias, fever of unknown origin or suspected haematological malignancy.

Which laboratory markers can support a diagnosis of haemolysis

Raised unconjugated bilirubin and LDH, reduced haptoglobin, raised reticulocyte count and sometimes haemoglobinuria.

What is iron deficiency anaemia's effect on red cells

Insufficient iron impairs haem synthesis, producing small, pale (microcytic, hypochromic) red cells.

What are key causes of iron loss or increased iron requirement mentioned in the lecture

Menstruation, pregnancy and gastrointestinal blood loss.

What is sideroblastic anaemia

A group of disorders where iron is not properly incorporated into haemoglobin during red-cell production, causing ineffective erythropoiesis and mitochondrial iron accumulation.

What are ring sideroblasts

Developing red cells with iron-loaded mitochondria arranged in a perinuclear ring, visible with Perls' (Prussian blue) stain.

What is adult haemoglobin A (HbA) made of

Two alpha and two beta chains: α₂β₂; it makes up >95% of haemoglobin after infancy.

What is fetal haemoglobin (HbF) made of

Two alpha and two gamma chains: α₂γ₂.

What is HbA2 made of, and what is its usual proportion

Two alpha and two delta chains: α₂δ₂; approximately 2–3.5%.

What is a haemoglobinopathy

An inherited disorder affecting haemoglobin structure (a qualitative variant) or the rate of globin-chain synthesis (a quantitative disorder such as thalassaemia).

How are haemoglobinopathies currently confirmed in NHS practice

High-performance liquid chromatography (HPLC) or capillary electrophoresis; family studies and DNA analysis may also be used when indicated.

What mutation causes sickle cell disease

A point mutation in the HBB beta-globin gene, GAG→GTG, replacing glutamate with valine at position 6 (Glu6Val).

How does HbS cause sickling

When deoxygenated, HbS polymerises and distorts red cells into a sickle shape.

How is sickle cell disease inherited

Autosomal recessively; HbAS is sickle trait and HbSS is sickle cell disease.

What can trigger a sickle-cell crisis

Hypoxia, acidosis, dehydration, infection/fever and exposure to extreme cold.

What is vaso-occlusion in sickle cell disease

Sickled cells obstruct blood vessels, causing painful episodes and possible tissue or organ injury.

Name important complications of sickle cell disease.

Painful vaso-occlusive crises, dactylitis, stroke risk, acute chest syndrome, infection due to functional hyposplenism, chronic haemolysis/jaundice, gallstones, leg ulcers and organ damage.

How does sickle cell trait differ from sickle cell disease

HbAS is generally asymptomatic with minimal clinical impact; HbSS causes substantial sickling, haemolysis and vaso-occlusive complications.

What is the characteristic blood-film appearance in sickle cell disease

Crescent-shaped sickle cells; target cells and polychromasia may also occur, with anisocytosis, poikilocytosis and sometimes nucleated red cells.

What tests are used to confirm sickle cell disease in current NHS practice

HPLC or capillary electrophoresis to quantify HbS, HbF and HbA2 and identify co-inherited variants.

What is the NHS screening approach for sickle cell disease and thalassaemia

Pregnant women in England are offered antenatal screening, ideally by 10 weeks; all newborns are offered screening via the heel-prick blood spot programme.

Why is early newborn screening for sickle cell disease important

It allows early clinical management, including penicillin prophylaxis and vaccination to reduce infection risk.

What is the genetic change in HbC

A beta-globin point mutation replacing glutamate with lysine at position 6.

How does HbC disease generally differ from sickle cell disease

Homozygous HbC disease is usually milder, with mild haemolytic anaemia, splenomegaly and target cells; HbC does not normally polymerise under low oxygen tension.

What is HbSC disease

A compound haemoglobinopathy in which HbS and HbC are inherited together; it can cause vaso-occlusive complications, often less frequently or severely than HbSS.

What are key management approaches for sickle cell disease

Hydration and analgesia during crises; hydroxycarbamide to increase HbF; transfusions for selected complications; infection prevention; stem-cell transplant for suitable patients; gene therapy is an emerging option.

How does sickle cell trait relate to malaria

HbAS provides some protection against severe Plasmodium falciparum malaria.

What causes thalassaemia

Inherited mutations or deletions reduce or abolish synthesis of alpha- or beta-globin chains, causing reduced haemoglobin production and chain imbalance.

What is the key pathophysiology of beta-thalassaemia

Reduced beta-chain production leaves excess alpha chains, which precipitate in red-cell precursors and cause ineffective erythropoiesis.

What do β⁰- and β⁺-thalassaemia mean

β⁰: no beta-globin chain production. β⁺: reduced beta-globin chain production.

How many alpha-globin genes are there, and where are they located

Four alpha-globin gene copies in total: two on each chromosome 16.

What are the clinical forms of alpha-thalassaemia by number of affected genes

One affected: silent carrier, usually asymptomatic. Two: alpha-thalassaemia trait, usually mild. Three: HbH disease, moderate haemolytic anaemia. Four: Hb Bart's hydrops fetalis, incompatible with life outside the womb.

What is HbH

A tetramer of four beta-globin chains (β₄), formed when alpha-globin production is severely reduced.

What is beta-thalassaemia minor (trait)

A heterozygous carrier state, usually with mild microcytosis and raised HbA2 on HPLC; often few or no symptoms.

What characterises beta-thalassaemia major

Severe, often transfusion-dependent anaemia presenting in infancy due to major reduction or absence of beta-chain production and ineffective erythropoiesis.

How is thalassaemia major managed

Regular blood transfusions and iron chelation to prevent iron overload; haemopoietic stem-cell transplant can be curative for suitable patients.

What is the key difference between sickle cell disease and thalassaemia

Sickle cell disease is a structural Hb variant that polymerises when deoxygenated; thalassaemia is reduced/absent globin-chain synthesis causing chain imbalance and ineffective erythropoiesis.

What causes megaloblastic anaemia

Impaired DNA synthesis, most commonly due to vitamin B12 or folate deficiency.

How does folate deficiency cause megaloblasts

DNA replication is delayed, so erythroblasts continue growing without dividing normally, producing large cells.

What are the main blood-film features of megaloblastic anaemia

Macrocytes, especially oval macrocytes; hypersegmented neutrophils (≥6 nuclear lobes); and anisopoikilocytosis.

What are causes of vitamin B12 deficiency mentioned in the lecture

Pernicious anaemia due to failure to produce intrinsic factor, dietary deficiency (rare) and malabsorption such as terminal ileal disease.

What is pernicious anaemia

A cause of vitamin B12 deficiency involving autoimmune destruction of gastric parietal cells and failure of intrinsic-factor secretion.

What neurological features may occur in vitamin B12 deficiency

Peripheral neuropathy, subacute combined degeneration of the spinal cord and psychological disturbance.

How is suspected pernicious anaemia investigated and treated

Investigations include B12/active B12 testing and intrinsic-factor antibodies; treatment is intramuscular vitamin B12 replacement.

What are causes of non-megaloblastic macrocytosis

Liver disease, alcohol excess, hypothyroidism and myelodysplasia.

How are haemolytic anaemias classified

Intrinsic (inherited) causes include membrane, enzyme and globin defects; extrinsic (acquired) causes include immune and non-immune destruction.

What is intravascular haemolysis

Red cells are destroyed within the circulation, releasing free haemoglobin; haptoglobin may fall and haemoglobinuria may occur.

What is extravascular haemolysis

Red cells are destroyed mainly by macrophages in the spleen or bone marrow; haem breakdown increases unconjugated bilirubin and may cause jaundice.

What laboratory pattern supports haemolysis

Raised unconjugated bilirubin, raised LDH, reduced haptoglobin and raised reticulocytes; haemoglobinuria suggests intravascular haemolysis.

What does a direct antiglobulin (direct Coombs) test detect

Evidence of antibodies or complement attached to red cells; it supports immune-mediated haemolysis.

What causes hereditary spherocytosis

Inherited defects in red-cell membrane cytoskeletal proteins, such as spectrin, ankyrin, band 3 or protein 4.1.

What does hereditary spherocytosis look like on a blood film

Small, round spherocytes lacking the normal central pallor, sometimes with polychromasia from reticulocytosis.

Why does hereditary spherocytosis cause haemolysis

Rigid, poorly deformable red cells are trapped and removed by the spleen, causing chronic extravascular haemolysis.

What is G6PD deficiency and what can trigger haemolysis

An X-linked enzyme deficiency that weakens antioxidant defence; oxidant drugs, fava beans and infections can trigger haemolysis.

What blood-film findings are associated with G6PD deficiency

Heinz bodies and bite cells.

What causes pyruvate kinase deficiency

An autosomal recessive enzyme deficiency that impairs glycolysis and ATP generation, causing chronic non-spherocytic haemolytic anaemia.

Give examples of acquired non-immune haemolysis.

Mechanical damage from prosthetic valves or microangiopathy (e.g. DIC/TTP), physical/chemical injury such as severe burns or lead toxicity, and infections such as malaria.

What causes acquired immune haemolysis

Antibodies reacting with red-cell antigens, including incompatible transfusion, autoantibodies and drug-induced immune reactions.

What is pancytopenia

Low levels of all three blood-cell lineages: red cells, white cells and platelets.

What is pure red cell aplasia (PRCA)

A rare condition where the bone marrow cannot make enough new red cells; causes include autoimmune processes and parvovirus B19 infection.

Name systemic diseases or processes that can contribute to anaemia.

Liver disease, renal failure with reduced erythropoietin, GI blood loss, heavy menstrual bleeding/fibroids, hypothyroidism, inflammation, cancer and overlapping causes in older adults.

What quality systems support reliability of NHS laboratory results in the lecture

Internal quality control (IQC) and external quality assessment (EQA), including UK NEQAS.