Learn — Haematology: anaemias, leukaemias, bleeding disorders & blood groups

3 notes · 3 questions on the topic

Anaemias — classification, iron deficiency, megaloblastic and haemolytic

Anaemia is a haemoglobin concentration below the reference for the person's age, sex and pregnancy state — below 13 g/dL in men, 12 in non-pregnant women, 11 in pregnancy and in children of 6 to 59 months — so that the blood carries too little oxygen for the tissues' needs. It is classified by cause (blood loss, reduced production, increased destruction) and by the red cell's size and colour on the smear and the indices (microcytic hypochromic, normocytic normochromic, macrocytic), and the three great types the paper asks — iron deficiency, megaloblastic and haemolytic — are told apart by the mean corpuscular volume, the reticulocyte count and a handful of tests the nurse draws and reads.

Morphological classification by mean corpuscular volume: microcytic hypochromic (MCV below 80 fL, MCH and MCHC low) — iron deficiency, thalassaemia, anaemia of chronic disease in part, sideroblastic anaemia and lead poisoning; normocytic normochromic (MCV 80 to 100) — acute blood loss, haemolysis, chronic disease, renal failure (low erythropoietin), aplastic anaemia and marrow infiltration; macrocytic (MCV above 100) — megaloblastic from vitamin B12 or folate deficiency, and non-megaloblastic from alcohol, liver disease, hypothyroidism and a high reticulocyte count.
Iron-deficiency anaemia is the commonest anaemia in the world and in India, from chronic blood loss (hookworm, menorrhagia, peptic ulcer, piles, a colonic carcinoma in the older man — always the first question), poor intake and absorption (a cereal diet, tea, coeliac disease, gastrectomy) and increased demand (growth, pregnancy); the laboratory shows a low haemoglobin, MCV, MCH and MCHC, a high red-cell distribution width, low serum iron and ferritin (below 15 micrograms per litre — the best single test), a high total iron-binding capacity and a low transferrin saturation, and a smear with microcytic hypochromic cells, pencil cells and anisopoikilocytosis; the marrow has no stainable iron.
The signs beyond pallor and fatigue: koilonychia (spoon nails), angular cheilitis, a smooth glossitis, pica (the craving for ice or clay), brittle hair, and the Plummer-Vinson syndrome of dysphagia from an oesophageal web; treatment is oral ferrous sulphate 200 mg (60 mg of elemental iron) two or three times a day, with a reticulocyte rise at 5 to 10 days and a haemoglobin rise of about 1 g/dL every two to three weeks, continued for three to six months after the haemoglobin is normal to refill the stores, or intravenous iron sucrose or ferric carboxymaltose when oral iron fails or is not tolerated.
Megaloblastic anaemia is defective DNA synthesis from lack of vitamin B12 or folate: B12 deficiency follows pernicious anaemia (autoantibodies to parietal cells and intrinsic factor), gastrectomy, ileal disease or resection, a strict vegan diet, the fish tapeworm and long-term metformin or proton-pump inhibitors, and adds subacute combined degeneration of the cord; folate deficiency follows pregnancy, malabsorption, alcohol, haemolysis and drugs such as phenytoin, methotrexate and trimethoprim; the smear shows oval macrocytes and hypersegmented neutrophils (five or more lobes — the earliest sign), the MCV is above 100, the count may be a pancytopenia, and the lactate dehydrogenase and unconjugated bilirubin are raised by ineffective erythropoiesis.
Treatment of megaloblastic anaemia is the vitamin that is missing — hydroxocobalamin 1000 micrograms intramuscularly, then maintenance for life in pernicious anaemia, and folic acid 5 mg a day — and never folate alone until B12 deficiency is excluded, because folate corrects the blood while the cord degenerates; potassium can fall in the first days of response and the reticulocytes rise by a week.
Haemolytic anaemia is premature destruction of red cells, inherited (hereditary spherocytosis with its raised osmotic fragility, G6PD deficiency with haemolysis after oxidant drugs, fava beans and infection, sickle cell disease and the thalassaemias) or acquired (autoimmune warm IgG and cold IgM haemolysis with a positive Coombs test, the microangiopathic haemolysis of disseminated intravascular coagulation, haemolytic-uraemic syndrome and prosthetic valves with schistocytes on the smear, malaria, drugs and transfusion reactions); the laboratory signature is a high reticulocyte count, raised unconjugated bilirubin and lactate dehydrogenase, a low haptoglobin, and haemoglobinuria when the haemolysis is intravascular, with jaundice, splenomegaly and pigment gallstones at the bedside.
The two that behave differently: aplastic anaemia is a pancytopenia with a hypocellular marrow after chloramphenicol, benzene, radiation, viral hepatitis or for no found cause — infection and bleeding, not just pallor, are its presentation — and the anaemia of chronic disease (infection, inflammation, malignancy) keeps iron locked in stores by hepcidin, so the serum iron is low but the ferritin is normal or high and the iron-binding capacity is low, and iron tablets do not help; the reticulocyte count separates all of them — low when the marrow is the problem, high when the cells are being lost or destroyed.

Leukaemias, lymphomas and bleeding disorders — haemophilia, ITP and DIC

The leukaemias are malignant clones of white-cell precursors that fill the marrow and spill into the blood, the lymphomas are malignant tumours of lymphoid tissue that form masses in nodes and organs, and the bleeding disorders are the failures of platelets, coagulation factors or vessel walls that turn a small injury into a haemorrhage. The paper asks their classification by cell and course, the named cells and chromosomes, the tests that separate a platelet problem from a clotting problem, and the inheritance of haemophilia; the nurse meets them as the child with bruises and fever, the man with a painful joint, and the patient whose count says no injections today.

Leukaemia is classified by course and cell: acute lymphoblastic leukaemia is the commonest cancer of childhood, peaking at 2 to 5 years, with lymphoblasts filling the marrow and a cure rate above 80 per cent with chemotherapy (the central nervous system and the testes are its sanctuary sites); acute myeloid leukaemia is a disease of adults with myeloblasts, Auer rods, and in its promyelocytic form a catastrophic disseminated intravascular coagulation treated with all-trans retinoic acid; both present with the failure of the marrow — anaemia (fatigue, pallor), neutropenia (fever, infection) and thrombocytopenia (bruising, gum and nose bleeding) — with bone pain and, in the acute leukaemias, gum hypertrophy and organ infiltration.
The chronic leukaemias: chronic myeloid leukaemia at 40 to 60 years carries the Philadelphia chromosome, t(9;22) with the BCR-ABL fusion gene, shows a massive splenomegaly and a very high white count with every stage of granulocyte and basophilia on the smear, is treated with imatinib and ends in blast crisis if it escapes; chronic lymphocytic leukaemia is the leukaemia of the elderly, indolent, with small mature lymphocytes and smudge cells, lymphadenopathy and autoimmune haemolysis; diagnosis in every leukaemia is the smear, the bone marrow aspiration and trephine from the posterior iliac crest, flow cytometry and cytogenetics.
Lymphoma: Hodgkin's lymphoma is diagnosed by the Reed-Sternberg cell (a large binucleate 'owl-eye' cell), has a bimodal age distribution, spreads contiguously from one node group to the next (usually starting in the neck), gives B symptoms — fever, drenching night sweats and weight loss above 10 per cent — the Pel-Ebstein fever and pain in the nodes after alcohol, is staged by the Ann Arbor system and is cured in most; non-Hodgkin's lymphomas are older, spread non-contiguously and to extranodal sites, are mostly B-cell — diffuse large B-cell the commonest, follicular with the t(14;18) BCL2 translocation, Burkitt's with the t(8;14) MYC translocation, Epstein-Barr virus, the jaw tumour of African children and the starry-sky pattern, and the MALT lymphoma of the H. pylori stomach.
Multiple myeloma is a malignancy of plasma cells in the elderly whose damage spells CRAB — hyperCalcaemia, Renal failure, Anaemia and Bone lesions (punched-out lytic lesions, vertebral collapse and pathological fractures) — with a monoclonal M protein on serum electrophoresis, Bence Jones light chains in the urine, rouleaux on the smear, more than 10 per cent plasma cells in the marrow, recurrent infections from the lack of normal immunoglobulin, and amyloidosis; the nursing hazards are the fracture from careless handling, the dehydration that tips the kidney, and the hypercalcaemia.
Bleeding from platelets shows as petechiae, purpura, mucosal bleeding and bleeding at once from cuts, and from coagulation factors as deep haematomas, haemarthroses and bleeding that starts hours after the injury; the tests separate them — platelet count and bleeding time for the platelet side, prothrombin time (the extrinsic pathway — warfarin, liver disease, vitamin K) and activated partial thromboplastin time (the intrinsic pathway — heparin, haemophilia) for the clotting side, with fibrinogen and D-dimer for consumption.
Platelet disorders: immune thrombocytopenic purpura — antiplatelet antibodies, acute and self-limiting in a child after a viral illness, chronic in young women, with an isolated thrombocytopenia and plentiful megakaryocytes in the marrow, treated with steroids, immunoglobulin and, when needed, splenectomy, and nursed with no intramuscular injections, no aspirin and a soft toothbrush; thrombotic thrombocytopenic purpura (fever, haemolysis, thrombocytopenia, renal and neurological signs — plasma exchange) and the haemolytic-uraemic syndrome of children after Escherichia coli O157 diarrhoea; disseminated intravascular coagulation, the consumption of platelets and factors in sepsis, abruption, amniotic fluid embolism, malignancy, trauma, burns and snakebite, with a low platelet count and fibrinogen, prolonged prothrombin and partial thromboplastin times, raised D-dimer and schistocytes, treated by treating the cause and replacing what is consumed; and von Willebrand disease, the commonest inherited bleeding disorder, autosomal dominant, with a long bleeding time and partial thromboplastin time, treated with desmopressin.
Haemophilia A is deficiency of factor VIII, X-linked recessive — affected sons of carrier mothers, no father-to-son transmission, daughters of an affected man all carriers — graded by the factor level (below 1 per cent severe, with spontaneous bleeds), with a prolonged activated partial thromboplastin time and a normal prothrombin time, bleeding time and platelet count; haemarthroses of the knees, elbows and ankles destroy the joints, and treatment is factor VIII concentrate (prophylaxis in the severe), desmopressin in mild disease, rest, ice, compression and elevation for a bleed, and never an intramuscular injection, aspirin or NSAID; haemophilia B is factor IX deficiency, the same in all but the missing factor, and vitamin K deficiency (the newborn, warfarin, malabsorption, antibiotics) prolongs the prothrombin time first because factor VII has the shortest half-life.

Blood groups, cross-matching and transfusion reactions

Blood groups are the inherited antigens on the red cell — the ABO system with its naturally occurring antibodies and the Rh system with the D antigen that matters in pregnancy — and cross-matching is the laboratory test that proves a donor's cells will not be destroyed by a recipient's serum before a unit is hung. Transfusion is a transplant of living tissue, and its reactions — from the harmless fever to the fatal ABO mismatch that is almost always a clerical error at the bedside — are the reason the nurse's two-person check, the first fifteen minutes and the four-hour limit exist.

The ABO system (Landsteiner, 1900): group A has A antigen and anti-B antibody, B has B antigen and anti-A, AB has both antigens and no antibody (the universal recipient of red cells), O has neither antigen and both antibodies (the universal donor of red cells, but its plasma is the most dangerous); the antibodies are naturally occurring IgM that do not cross the placenta, which is why ABO incompatibility of mother and baby is usually mild; in India O and B are the commonest groups and AB the rarest; the Bombay group lacks even the H antigen and can receive only Bombay blood.
The Rh system turns on the D antigen: about 94 per cent of Indians are Rh positive; anti-D is not natural but immune, formed after an Rh-negative person meets D-positive cells by transfusion or pregnancy, and it is IgG, which crosses the placenta and destroys the fetus's red cells — haemolytic disease of the newborn, prevented by anti-D immunoglobulin to the Rh-negative mother at 28 weeks and within 72 hours of delivery, abortion or any sensitising event; the direct Coombs test finds antibody already on the red cells (haemolytic disease, autoimmune haemolysis) and the indirect Coombs test finds antibody in the serum (antenatal screening, cross-matching).
Grouping and cross-matching: forward grouping tests the patient's cells with anti-A, anti-B and anti-D, reverse grouping tests the serum against known cells, and the two must agree; the antibody screen looks for the irregular antibodies (Kell, Duffy, Kidd) and the major cross-match mixes the donor's red cells with the recipient's serum — the test that matters — while the minor cross-match tests the donor's plasma against the recipient's cells; the sample for grouping is drawn, labelled at the bedside with the patient's identifiers, and never pre-labelled.
Donation and screening: a donor is 18 to 65 years, at least 45 to 50 kg, with a haemoglobin of 12.5 g/dL or more, gives 350 or 450 mL, and waits three months (men) or four (women) between donations; every unit in India is tested for HIV 1 and 2, hepatitis B surface antigen, hepatitis C, syphilis and malaria; whole blood and packed cells are stored at 2 to 6 °C for 35 days in CPDA-1 and 42 days with additive solution, platelets at 20 to 24 °C with continuous agitation for 5 days, fresh frozen plasma at minus 30 °C or below for a year, and cryoprecipitate likewise.
Components and their use: packed red cells for anaemia and blood loss (one unit raises the haemoglobin by about 1 g/dL), platelet concentrates for bleeding or a count below 10,000 to 20,000 (one random-donor unit raises the count by 5,000 to 10,000), fresh frozen plasma for coagulation factor deficiency and warfarin reversal (10 to 15 mL/kg), cryoprecipitate for fibrinogen, factor VIII and von Willebrand factor, granulocytes rarely, and albumin; irradiated components for the immunocompromised to prevent graft-versus-host disease, leucodepleted components to prevent febrile reactions and cytomegalovirus.
The transfusion procedure that prevents the fatal error: consent; a two-person check at the bedside of the patient's identity band against the unit's label, group, number and expiry; an 18-gauge cannula with a filtered blood set and normal saline only — never dextrose or Ringer's lactate, never a drug in the line; baseline vital signs, a slow start of about 2 mL a minute for the first 15 minutes with the nurse present, vital signs at 15 minutes and then hourly, the unit started within 30 minutes of leaving the refrigerator and completed within 4 hours, and the empty bag and the reaction form kept if anything goes wrong.
Reactions: acute haemolytic (ABO incompatibility, usually a bedside identification error — fever, chills, back or flank pain, chest tightness, hypotension, haemoglobinuria, disseminated intravascular coagulation and renal failure within minutes: stop, keep the line open with saline, send the unit and fresh samples, and maintain the urine output above 100 mL an hour), febrile non-haemolytic (the commonest — antibodies to donor leucocytes, a rise of 1 °C or more within 4 hours: stop, antipyretic, leucodepleted units next time), allergic urticaria (plasma proteins — antihistamine, may resume slowly) and anaphylaxis (IgA deficiency — adrenaline), transfusion-related acute lung injury (non-cardiogenic pulmonary oedema within 6 hours from donor antibodies — the leading cause of transfusion death), circulatory overload in the elderly and the failing heart (slow rate, diuretic), bacterial contamination (platelets), citrate hypocalcaemia and hyperkalaemia in massive transfusion, hypothermia from cold blood; delayed reactions are delayed haemolysis at 3 to 14 days, alloimmunisation, graft-versus-host disease, post-transfusion purpura, iron overload after many units and the transmitted infections.

Free today: the 10-question daily quiz · the NORCET 11 recall paper · what ₹999 unlocks — once, no auto-renewal.