Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.
Recognise hypocellular marrow failure, exclude reversible and clonal mimics, stabilise infection and bleeding, and choose transplant or immunosuppression according to severity, age and donor status.
Acquired aplastic anaemia usually reflects cytotoxic T-cell attack on haematopoietic stem cells, leaving fatty hypocellular marrow and reduced production across erythroid, myeloid and megakaryocytic lineages. Peripheral destruction is not the primary mechanism, so reticulocytes are low rather than compensatorily raised. The clinical picture depends on which line reaches danger first. Profound neutropenia drives bacterial and fungal infection, thrombocytopenia drives mucosal or internal bleeding, and anaemia develops with fatigue, tachycardia and cardiac strain.
Aplastic anaemia is a diagnosis of mechanism and exclusion. Repeat a credible count and examine the film for blasts, dysplasia, fragments or megaloblastosis. Assess B12, folate, liver disease, viral infection, pregnancy and drug or occupational exposure. Bone-marrow trephine is essential because an aspirate alone may be dilute and misleading. Cytogenetic and molecular findings, dysplasia or fibrosis may favour hypoplastic myelodysplastic syndrome. In younger people, physical features and family history guide testing for Fanconi anaemia, telomere biology disorders and other inherited syndromes before transplant conditioning.
Autoreactive T cells and inhibitory cytokines suppress or destroy haematopoietic stem cells. A specific trigger is often not found despite careful medicine, infection and exposure review.
Rare medicine reactions, benzene, radiation and hepatitis-associated syndromes can precede marrow failure; temporal association requires specialist causality assessment rather than assuming every concurrent medicine is responsible.
Fanconi-pathway, telomere and other germline disorders may first appear in adolescence or adulthood and materially change donor choice, conditioning intensity and family counselling.
Loss of multipotent progenitors reduces production of red cells, granulocytes and platelets together, producing a fatty hypocellular marrow and low circulating reticulocytes.
Reduced innate cellular defence permits rapidly progressive bacterial infection and, when prolonged, invasive fungal disease, sometimes with little inflammatory response or localising pus.
Insufficient megakaryopoiesis produces petechiae and mucosal bleeding and can progress to retinal, gastrointestinal or intracranial haemorrhage at very low counts.
Surviving stem-cell clones may acquire growth advantages, explaining PNH populations and later myelodysplastic or leukaemic evolution in a minority of patients.
Anaemia, neutropenia and thrombocytopenia occur with an inappropriately low absolute reticulocyte count and without a crowded leucoerythroblastic film.
Fever, oral ulceration or perianal pain may be the only evidence of severe neutropenic infection and deserves immediate assessment.
Petechiae, gum bleeding, epistaxis or menorrhagia reflect thrombocytopenia; headache or focal neurology raises critical intracranial bleeding.
Hypotension, confusion, hypoxia or fever with profound neutropenia requires empirical antibiotics and resuscitation before diagnostic completion.
Substantial nodes, splenomegaly or bone tenderness argues against uncomplicated aplasia and prompts investigation for malignant or systemic disease.
Cytopenias with hypocellularity can arise from myelodysplastic neoplasia; convincing dysplasia, abnormal cytogenetics, somatic mutation patterns and age-dependent context guide specialist distinction.
Leukaemia may present with pancytopenia even without circulating blasts; marrow morphology, immunophenotyping and genetics identify malignant replacement requiring an entirely different urgent pathway.
Severe B12 or folate deficiency can cause pancytopenia, macro-ovalocytes, hypersegmented neutrophils and biochemical ineffective erythropoiesis but usually produces a cellular megaloblastic marrow.
Sepsis, hypersplenism and thrombotic microangiopathy lower circulating cells through sequestration or destruction; examination, film, coagulation and haemolysis findings differ from pure production failure.
Profound neutropenia can turn minor mucosal or line-associated infection into shock rapidly, while fever or inflammatory markers may be muted and treatment cannot await culture confirmation.
Severe thrombocytopenia may cause gastrointestinal, retinal, pulmonary or intracranial bleeding, with risk modified by fever, medicines, trauma and platelet function.
Repeated support can produce alloimmunisation, iron loading and reactions; component selection also matters for future transplantation and prevention of transfusion-associated graft-versus-host disease.
A PNH clone, myelodysplastic change or acute myeloid leukaemia can emerge during follow-up, signalled by new count patterns, haemolysis, dysplasia or cytogenetic abnormalities.
A very low absolute reticulocyte count distinguishes marrow output failure from the compensatory response expected in peripheral haemolysis.
A dilute aspirate may look empty for technical reasons; architectural cellularity and exclusion of infiltration require an adequate core biopsy.
A tiny clone in immune aplasia can mark pathobiology without producing classical haemolysis or automatically requiring complement inhibition.
Transfusion choices, germline testing and HLA search can influence curative options long before supportive care becomes difficult.
Waiting for marrow biopsy before treating neutropenic sepsis.
Calling a dilute aspirate diagnostic without trephine architecture.
Missing inherited failure in a young adult.
Equating a small PNH clone with classical PNH.
Giving unselected blood components before transplant discussion.
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A patient with newly diagnosed aplastic anaemia has a small PNH clone on high-sensitivity flow cytometry but no thrombosis, haemoglobinuria or biochemical intravascular haemolysis. Which interpretation is most appropriate?
National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.
Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes
Infusion reactions, serum sickness, anaphylaxis, infection and worsening cytopenias require monitored administration; product selection and viral screening follow the centre protocol.
Nephrotoxicity, hypertension, magnesium loss, neurotoxicity, infection and numerous CYP3A interactions require laboratory and clinical surveillance; abrupt early withdrawal promotes relapse.
Monitor liver tests, marrow morphology, cytogenetics and thrombosis; it is not a substitute for urgent antibiotics or transfusion support during dangerous cytopenia.