Haematology & Blood Transfusion Pathology: OmpathStudy

SEMESTER THREE — REMAINING TOPICS (7–11) 7. Myelodysplastic Syndromes (MDS) - Clonal disorder of haemopoietic stem cells → dysplastic (abnormally formed), ineffective blood cell production, despite a normal or hypercellular marrow. Key concept (must-know, often tested as a contrast question): "ineffective haemopoiesis" — marrow is busy, but cells die before release or don't function properly → peripheral cytopenias despite a cellular marrow. This is the opposite picture from aplastic anaemia (hypocellular marrow), a classic exam contrast. Cause: mostly idiopathic (de novo), or secondary/therapy-related (prior chemotherapy or radiotherapy — "t-MDS"). More common in older adults. Clinical features : result from cytopenias — fatigue/pallor (anaemia), infections (neutropenia), bleeding (thrombocytopenia). No major organomegaly typically. Blood film/marrow clues (must-know dysplastic features): Red cells — macrocytosis, ring sideroblasts (iron-loaded mitochondria around the nucleus) Neutrophils — hypogranular cytoplasm, hypo-segmented nuclei ( pseudo-Pelger-Huët cells ) Megakaryocytes — micromegakaryocytes, abnormal nuclear lobulation Diagnosis: cytopenias + dysplasia on marrow morphology + cytogenetics (e.g. del(5q) — a favourable-prognosis subtype, also must-know). Important progression fact : MDS can transform into AML — a key link question connecting this topic back to WBC malignancies. Management: supportive (transfusions, growth factors), hypomethylating agents (azacitidine), allogeneic stem cell transplant (only curative option, for eligible/fit patients). 8. Stem Cell Transplantation Replacing diseased/failed marrow with healthy haemopoietic stem cells. Two broad types — must-know distinction: Autologous — patient's own stem cells, harvested before treatment, re-infused after high-dose therapy (used in myeloma, some lymphomas). No risk of GVHD or rejection but no "graft-versus-tumour" effect either. Allogeneic — stem cells from a donor (sibling, unrelated matched donor, or cord blood). Curative potential is higher (graft-versus-leukaemia effect) but carries GVHD risk. Process sequence (essay skeleton): Stem cell collection — peripheral blood (after mobilisation with G-CSF) or bone marrow harvest Conditioning — chemotherapy ± radiotherapy to destroy the patient's own marrow/immune system, creating "space" and eliminating disease Infusion of stem cells — engraftment follows over 2–4 weeks Supportive care during the pancytopenic window (infection prophylaxis, transfusion support) Complications (must-know list): Graft failure/rejection Infections (bacterial, fungal, viral reactivation — e.g. CMV) during the immunosuppressed period Graft-versus-host disease (GVHD) — donor T cells attack recipient tissues; acute (skin, gut, liver) vs chronic forms — only a risk in allogeneic transplant Veno-occlusive disease of the liver (from conditioning toxicity) Long-term: infertility, secondary malignancy, organ toxicity from conditioning regimens Indications: leukaemias (esp. high-risk/relapsed), aplastic anaemia, myeloma, lymphoma, some inherited disorders (thalassaemia major, sickle cell disease). 9. Haematological Changes in Systemic Disease Blood often reflects disease happening elsewhere in the body — a classic "clinicopathological correlation" essay theme. Anaemia of chronic disease (must-know mechanism) : chronic inflammation → hepcidin release from the liver → traps iron in macrophages/reduces gut iron absorption → functional iron deficiency despite normal/high body iron stores. Seen in chronic infection, autoimmune disease (e.g. rheumatoid arthritis), malignancy, chronic kidney disease. Renal disease — reduced erythropoietin production → normocytic anaemia; uraemia can also impair platelet function (bleeding tendency despite normal platelet count). Liver disease — reduced clotting factor synthesis (all factors except VIII) → raised PT/aPTT; macrocytosis; thrombocytopenia from hypersplenism (portal hypertension). Connective tissue/autoimmune disease (e.g. SLE) — can cause autoimmune haemolytic anaemia, leucopenia, thrombocytopenia (cytopenias are part of diagnostic criteria for SLE). Malignancy (non-haematological) — anaemia of chronic disease, marrow infiltration by metastases, paraneoplastic effects (e.g. polycythaemia from renal cell carcinoma producing ectopic EPO). Must-know exam link : anaemia of chronic disease vs iron deficiency anaemia is a frequently tested differentiation — both can be microcytic, but ferritin is low in true iron deficiency and normal/high in anaemia of chronic disease (since ferritin is also an acute-phase protein). 10. Pregnancy and Neonatal Haematology Normal physiological changes in pregnancy (must-know — easily mistaken for pathology): Plasma volume increases more than red cell mass → dilutional/physiological anaemia — Hb falls but this is expected and not always pathological Mild thrombocytopenia can occur (gestational thrombocytopenia) — usually benign Procoagulant state — pregn