Haematology

A reduced haemoglobin concentration, not a diagnosis in itself — the task is to find the cause, and the MEAN CELL VOLUME (MCV) is the organising principle. Microcytic (iron deficiency, thalassaemia, sideroblastic), normocytic (acute blood loss, chronic disease, haemolysis, renal, marrow failure) and macrocytic (B12/folate = megaloblastic; alcohol, hypothyroid, liver, myelodysplasia = non-megaloblastic). The blood film and reticulocyte count refine it.

The commonest anaemia worldwide — a microcytic, hypochromic anaemia from depleted iron stores. The cause matters more than the number: in adults (especially men and post-menopausal women) it signals occult GI blood loss / malignancy until proven otherwise; in menstruating women, menorrhagia; consider coeliac disease (malabsorption) and dietary deficiency. Treat with oral iron and find and treat the cause.

Deficiency of vitamin B12 or folate impairs DNA synthesis, producing a megaloblastic macrocytic anaemia (hypersegmented neutrophils, oval macrocytes). B12 deficiency is most often pernicious anaemia (autoimmune loss of intrinsic factor) and uniquely causes neurological disease — subacute combined degeneration of the cord. The cardinal rule: replace B12 BEFORE folate, because giving folate alone in B12 deficiency can precipitate/worsen the neuropathy.

Anaemia from premature red-cell destruction, with a compensatory reticulocytosis and the biochemical signature of haemolysis (raised LDH and bilirubin, low haptoglobin). Split by site (intra- vs extravascular) and cause: inherited (hereditary spherocytosis, G6PD deficiency, sickle/thalassaemia) vs acquired (autoimmune — warm/cold, mechanical, drug-induced, microangiopathic). The direct antiglobulin test (DAT/Coombs) separates immune from non-immune.

An autosomal recessive haemoglobinopathy (HbSS) in which a β-globin point mutation produces haemoglobin S that polymerises when deoxygenated, sickling red cells and causing chronic haemolysis and vaso-occlusive crises. Affects people of African/Caribbean (and Mediterranean/Middle-Eastern/Indian) ancestry. Detected on newborn screening; management is prophylaxis (penicillin, vaccines, hydroxycarbamide) plus prompt crisis treatment. (Paediatric detail is on child_health.)

Inherited disorders of reduced or absent globin-chain synthesis — alpha (α-chain) or beta (β-chain) thalassaemia. They range from a clinically silent/microcytic-trait picture to transfusion-dependent major (β-thalassaemia major — severe anaemia, extramedullary haematopoiesis, iron overload). The key practical points: thalassaemia trait is a microcytic anaemia with NORMAL ferritin (don't mistake it for iron deficiency), and transfusion-dependent disease causes iron overload needing chelation.

Aggressive malignancies of haematopoietic precursors in which immature BLASTS replace the marrow, causing rapid marrow failure (anaemia, neutropenia, thrombocytopenia). Acute lymphoblastic leukaemia (ALL) is commonest in children; acute myeloid leukaemia (AML) predominates in adults. Presentation is over days–weeks with the consequences of cytopenias plus blasts on the film/marrow; it is a haematological emergency (neutropenic sepsis, bleeding, tumour lysis).

Indolent leukaemias of MATURE cells, often found incidentally on a routine FBC. Chronic lymphocytic leukaemia (CLL) is a clonal expansion of mature B-lymphocytes (lymphocytosis, smear/smudge cells) in older adults. Chronic myeloid leukaemia (CML) is a myeloproliferative disorder with the Philadelphia chromosome (BCR-ABL, t(9;22)) causing a raised neutrophil/myeloid count and massive splenomegaly, transformed by targeted tyrosine kinase inhibitors.

Malignancies of lymphocytes presenting as lymphadenopathy ± systemic 'B symptoms'. Hodgkin lymphoma (bimodal age, Reed-Sternberg cells, contiguous nodal spread, alcohol-induced node pain) is highly curable. Non-Hodgkin lymphoma is a heterogeneous group (indolent e.g. follicular vs aggressive e.g. diffuse large B-cell) that is commoner, more variable in behaviour, and more often extranodal/disseminated. Diagnosis is by lymph-node biopsy; staging guides treatment.

A malignancy of plasma cells producing a monoclonal immunoglobulin (paraprotein) and causing end-organ damage summarised by CRAB: hyperCalcaemia, Renal impairment, Anaemia, Bone lesions (lytic). It affects older adults and presents with bone pain/fractures, anaemia, renal failure or recurrent infection. Diagnosis combines paraprotein (serum/urine electrophoresis, free light chains), marrow plasmacytosis and end-organ damage.

Clonal disorders of the marrow producing too many mature cells of one or more myeloid lineages: polycythaemia vera (red cells, JAK2 V617F), essential thrombocythaemia (platelets), and primary myelofibrosis (marrow fibrosis → cytopenias + massive splenomegaly). The shared hazards are thrombosis (and bleeding) and transformation to acute leukaemia/myelofibrosis. Polycythaemia must be split into true (primary/secondary) vs relative.

A reduction in all three blood cell lines (anaemia + neutropenia + thrombocytopenia). The causes group into reduced production (aplastic anaemia, marrow infiltration by leukaemia/myeloma/metastasis/fibrosis, B12/folate deficiency, drugs/chemo/radiation) and increased peripheral destruction/pooling (hypersplenism, severe autoimmune disease). Aplastic anaemia is a hypocellular ('empty') marrow with pancytopenia and no blasts — bone marrow examination is the key step.

A reduced neutrophil count (commonly from chemotherapy, also marrow failure, drugs, autoimmune, severe infection). NEUTROPENIC SEPSIS — a temperature >38°C (or other signs of sepsis) in a patient with neutrophils ≤0.5 ×10⁹/L (or <1.0 and falling) — is an oncological EMERGENCY: the inflammatory response is blunted, so deterioration is rapid, and empirical IV antibiotics must be given within 1 hour without waiting for cultures or imaging.

A low platelet count, causing a platelet-type bleeding pattern (mucocutaneous — petechiae, purpura, epistaxis, menorrhagia). Causes split into reduced production (marrow failure/infiltration, drugs, alcohol, B12/folate), increased destruction (immune thrombocytopenia/ITP, drug-induced, DIC, TTP/HUS) and sequestration (hypersplenism). ITP is an autoimmune (often post-viral in children) isolated thrombocytopenia and a diagnosis of exclusion.

Inherited bleeding disorders of the coagulation cascade. Haemophilia A (factor VIII) and B (factor IX) are X-linked recessive and cause a deep-bleeding pattern (haemarthroses, muscle haematomas) with a prolonged APTT and normal PT. Von Willebrand disease (commonest inherited bleeding disorder, usually autosomal dominant) causes a platelet-type mucocutaneous bleeding pattern through deficient/defective von Willebrand factor (which also carries factor VIII).

An increased tendency to thrombosis from inherited or acquired hypercoagulability. Inherited: factor V Leiden (commonest — activated protein C resistance), prothrombin gene mutation, protein C/S and antithrombin deficiency. Acquired: antiphospholipid syndrome, malignancy, pregnancy/oestrogen, nephrotic syndrome, surgery/immobility. It matters when thrombosis is unprovoked, recurrent, at a young age, at an unusual site, or with recurrent miscarriage — prompting selective testing.

A consumptive coagulopathy in which widespread activation of coagulation (triggered by sepsis, malignancy, obstetric emergencies, trauma, or transfusion reaction) consumes platelets and clotting factors and deposits microthrombi — causing BOTH bleeding (from depletion) and thrombosis/organ ischaemia simultaneously. It is always secondary, so the priority is treating the underlying cause alongside supportive blood-product replacement.

Adverse reactions to blood-component transfusion, ranging from mild to fatal. They are recognised by their TIMING and features: acute haemolytic (ABO incompatibility — a never-event from a clerical error), febrile non-haemolytic, allergic/anaphylactic, TACO (circulatory overload), TRALI (transfusion-related acute lung injury), and delayed haemolytic/infection. The immediate response is STOP the transfusion and assess (ABCDE), then manage by the specific type.

Reduced or absent splenic function — after splenectomy (trauma, ITP, spherocytosis), or functional (sickle cell disease, coeliac disease, inflammatory bowel disease). The spleen clears encapsulated organisms, so hyposplenic patients are at lifelong risk of OVERWHELMING POST-SPLENECTOMY INFECTION (OPSI) — fulminant sepsis with encapsulated bacteria (pneumococcus, Haemophilus, meningococcus). Prevention is vaccination + prophylactic penicillin + patient awareness.

Inherited defects in components of the immune system, classified by the limb affected: antibody/B-cell (commonest — e.g. common variable immunodeficiency, selective IgA deficiency), T-cell/combined (e.g. DiGeorge, SCID), phagocyte (chronic granulomatous disease) and complement deficiencies. The pattern of infection points to the defect, and recurrent/severe/unusual/persistent infections (the 'SPUR' pattern) should prompt investigation rather than repeated courses of antibiotics.

The blood film is where a numerical abnormality becomes a diagnosis. Recognising a handful of morphologies — and knowing which of them demand a phone call the same day — is the practical skill being tested.