1 / 55

Haematology

Haematology. Chris Mayo & Henry Greenslade. Aims of this lecture. Recap of blood physiology A look at common blood cancers Have a structure for looking at anaemia Odd bits and bobs e.g. haemoglobinopathies /bleeding disorders.

barneyt
Télécharger la présentation

Haematology

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Haematology Chris Mayo & Henry Greenslade

  2. Aims of this lecture • Recap of blood physiology • A look at common blood cancers • Have a structure for looking at anaemia • Odd bits and bobs e.g. haemoglobinopathies/bleeding disorders The Peer Teaching Society is not liable for false or misleading information…

  3. Physiology recap • Blood components – production and function of • WBC, RBC, Platelets • Bleeding and coagulation • platelet plug, secondary coagulation. Wikipedia.org The Peer Teaching Society is not liable for false or misleading information…

  4. RBC Recap • Precursor to erythrocytes? • Structure of haemoglobin ? • Life span of a RBC = 120 days • RBC’s are mopped up in spleen, liver, bone marrow – what is released ? The Peer Teaching Society is not liable for false or misleading information…

  5. More haemoglobin physiology! The Peer Teaching Society is not liable for false or misleading information…

  6. White blood cell recap • WBC’s consist of granulocytes, monocytes, lymphocytes • The majority of WBCs are from CFU- GM (granulocyte, monocyte) – these are committed stem cells that produce the majority of WBCs. • Lymphoid stem cells produce B cells and T cells separately The Peer Teaching Society is not liable for false or misleading information…

  7. Origins of blood cells Wikipedia.org The Peer Teaching Society is not liable for false or misleading information…

  8. Neutrophils • Neutrophils are constantly moving in + out of circulation • Most common WBC • ↑ in inflammation, infection, acute illness, steroid therapy, myeloid leukaemia • ↓ in viral infection (e.g. influenza, measles, EBV), bone marrow failure, sepsis, drugs (e.g. chemotherapy), decreased B12/folate The Peer Teaching Society is not liable for false or misleading information…

  9. Eosinophils, Basophils • Eosinophils – 5% of circulating white cells. These cells are bi-lobed in appearance. Raised in allergy, parasitic infections, lymphoma • Basophils – 1% of WBC , typically associated with hypersensitivity reactions. Raised in most chronic inflammatory conditions. The Peer Teaching Society is not liable for false or misleading information…

  10. Neutrophils • Neutrophils are constantly moving in + out of circulation • Most common WBC • ↑ in inflammation, infection, acute illness, steroid therapy, myeloid leukaemia • ↓ in viral infection (e.g. influenza, measles, EBV), bone marrow failure, sepsis, drugs (e.g. chemotherapy), decreased B12/folate The Peer Teaching Society is not liable for false or misleading information…

  11. Lymphocytes • Broken into T cells and B cells • T lymphocytes (80%) mediate cellular immunity • B lymphocytes mediate humoral immunity (antibody-mediated immunity) • Raised in viral infection, inflammation, lymphocytic leukaemia • Depleted in HIV, chemotherapy etc. The Peer Teaching Society is not liable for false or misleading information…

  12. T cells + B cells • Cytotoxic T cells (CD8+) – directly kill targets (body’s own infected cells/cancer cells) via enzymes. These require activation via… • T helper cells (CD4+) – when activated – stimulate both B cell and CD8+ T cell activation. • NK cells – these are lymphocytes – target virus infected cells and cancer cells. These do not need activation • B cells – once stimulated – differentiate into plasma cells and begin churning out antibodies The Peer Teaching Society is not liable for false or misleading information…

  13. Platelets and clotting • Platelets originate from megakaryocytes – they bud off into the circulation • They play a major role in clotting • There are two main steps to clotting • 1. The formation of a platelet plug – this is temporary and helps to stabilise the injury • 2. The clotting cascade then strengthens the platelet plug by causing coagulation – ultimately by producing fibrin at the end of two long complex pathways. The Peer Teaching Society is not liable for false or misleading information…

  14. Coagulation factors • There are several – some more important than others • Almost all of them (except V) are synthesised in the liver • Haemophilia A and B caused by deficiency (8 + 9) • 2, 7, 9, and 10 are clotting factors that depend on vitamin K – why is this important? The Peer Teaching Society is not liable for false or misleading information…

  15. Case Scenario #1 • Logan is a 10 year old boy who is brought into the GP's by his mum. He is complaining of a limp that has been present for 2 weeks now. You notice he appears unwell and pale, and when you check his records you notice he has attended the practice a couple of times in the last few weeks with recurrent URTI's. The Peer Teaching Society is not liable for false or misleading information…

  16. Questions • What is the diagnosis? • What is the pathology behind his symptoms ? • What investigations do you want to do ? (3) The Peer Teaching Society is not liable for false or misleading information…

  17. The acute leukaemias • ALL – mainly a childhood disease • AML – typically older adults • Both present in similar ways – e.g. patients that rapidly become unwell, with dramatic symptoms e.g. bone marrow failure • Don't worry about treatment too much The Peer Teaching Society is not liable for false or misleading information…

  18. Investigations • FBC – important to assess bone marrow function, response to treatment • Blood film • U+E, LFT’s – need baseline prior to starting chemotherapy • Clotting! • Bone marrow biopsy The Peer Teaching Society is not liable for false or misleading information…

  19. Basics of treatment • Induction – this aims to remove 99% of leukaemic cells and restore previous bone marrow function • Consolidation – Lower intensity treatment aimed at removing that 1% • Maintenance – Background therapy taken for 2-3 years to maintain remission • (ALSO CNS Prophylaxis) The Peer Teaching Society is not liable for false or misleading information…

  20. Chronic leukaemias • CML and CLL – these are mature cells • The medical school like to ask about CML – so will focus on this • These are generally more slow-growing cancers vs. acute but different grades exist The Peer Teaching Society is not liable for false or misleading information…

  21. CML – things to know • Most patients will have the Philadelphia chromosome! • Accumulation of myeloid cells • CML is often picked up incidentally e.g. random FBC • Other symptoms are quite vague • Chronic  accelerated  blast crisis Treat with Imatinib – a tyrosine kinase inhibitor The Peer Teaching Society is not liable for false or misleading information…

  22. CLL – quick recap • CLL is associated with mature B cell accumulation. • It is the most common leukaemia • Seen as lymphocytosis on blood film. • Associated with enlarged rubbery non-tender nodes. • 1/3 stable, 1/3 slow progression, 1/3 active progression of disease. • Treatment is with chemotherapy/radiotherapy/stem-cell transplant. The Peer Teaching Society is not liable for false or misleading information…

  23. Hodgkin’s lymphoma • What makes a Hodgkin’s lymphoma different from a NHL? – Reed-Steinberg Cells • Typically seen in younger people e.g. 20-40 year olds • Most commonly – lymph node enlargement with systemic symptoms. • EBV is a possible cause • Classified according to Ann Arbor system • Treatment with chemotherapy The Peer Teaching Society is not liable for false or misleading information…

  24. Ann Arbor system http://www.physio-pedia.com/Hodgkin%27s_Lymphoma_Case_Study The Peer Teaching Society is not liable for false or misleading information…

  25. Case study #2 • Charles is a 72 year old man who is brought into hospital by ambulance. This morning he had difficulty getting out of bed and had been incontinent of urine. On examination he has weak power in his legs. He has been complaining of back pain for several months but has not seen his GP. His ESR and Calcium are markedly raised. The Peer Teaching Society is not liable for false or misleading information…

  26. Questions • What is the likely diagnosis? • What do you think his U+E’s might show? • How do you confirm the diagnosis? • What is the characteristic protein found in the urine of some patients? The Peer Teaching Society is not liable for false or misleading information…

  27. Multiple myeloma • Malignant proliferation of plasma cells • Typically causes bone pain, tiredness, night sweats etc. • Hyperviscosity – causes strokes, confusion, blurred vision, bleeding. • Acute kidney injury due to light chain deposition. • Investigate – as above. • Treatment – analgesia, bisphosphonates, chemotherapy. The Peer Teaching Society is not liable for false or misleading information…

  28. Emergencies in Haematology • Don’t worry too much about specifics • Spinal cord compression – 5% of all myeloma patients • SVC obstruction – might see this in lymphoma • Neutropenic sepsis – dangerous - leukaemia/chemotherapy side effects  • Tumour lysis syndrome – typically at the start of chemotherapy • Hypercalcaemia – typically due to lytic lesions.  The Peer Teaching Society is not liable for false or misleading information…

  29. How to look at anaemias • ↓Hb • Pathophysiology: • ↓ RBC production • ↑ RBC destruction • ↑ RBC loss • General signs and symptoms • Lethargy, SOB, Reduced exercise tolerance, headache pallor • Severe disease: Angina, tachycardia, systolic flow murmur The Peer Teaching Society is not liable for false or misleading information…

  30. Relevant haematology investigations • Hb: 13-17.5g/L in men, 11.5-16g/L in women • MCV: 75-95 fL • Haematocrit: 0.4-0.52 in men, 0.36-0.47 in women • Ferritin: 10-120g/uL **STORAGE** • Transferrin saturation: 20-45% **TRANSport** • TIBC: 49-78mmol/L **Ability of ferritin to take iron** • Film to assess morphology of RBCs The Peer Teaching Society is not liable for false or misleading information…

  31. Classes of anaemia • Microcytic - <76fl – Due to reduced Hb production • Iron deficiency • Thalassaemia • Haemaglobinopathies • (Sideroblastic anaemia) • Normocytic – 77-95fl • Acute blood loss • Haemolysis • Renal failure • Chronic disease • Cancer The Peer Teaching Society is not liable for false or misleading information…

  32. Classes of anaemia • Macrocytic - >96fl – Due to reduced synthesis of RBCs • B12 deficiency • Folate deficiency • Alcohol excess • Liver/ thyroid disease • Anti folate medication The Peer Teaching Society is not liable for false or misleading information…

  33. Chris’s Case #1 A 44-year-old Asian female presents with a two-month history of shortness ofbreath and lethargy. She denies any intolerance to the cold or any changes in her weight and on examination appears slightly pale. She states that she has recently become a vegetarian. She complains of a sore tongue and on inspection she has kolionychia. A blood film shows the presence of elliptocytes and blood results show the following: Haemoglobin: 9.9 g/dLMean cell volume (MCV): 75 fLFerritin: Low What is kolionychia? What is the diagnosis? What would the TIBC be? What is the likely cause? The Peer Teaching Society is not liable for false or misleading information…

  34. Iron deficiency anaemia Specific Si/Sy: Konlionchia; Glossitis; Angular stomitis Film: • Normal • Anaemic • Microcytic, Hypochromic with anisocytosis and polikocytosis The Peer Teaching Society is not liable for false or misleading information…

  35. Iron deficiency anaemia • Ix: FBCs, Film ?Malignancy – OGD, Colonsocopy, Barium enema • Mx: • Treat underlying condition if there is one • Iron replacement e.g. ferrous sulphate for ~3/12 (check response in 2-4/52) • Transfuse if v. low (<70g/L) or earlier with significant cardiac morbidity e.g. severe heart failure The Peer Teaching Society is not liable for false or misleading information…

  36. Alpha and Beta Thalassaemia 2 main types of haemoglobin • HbA (adult haemoglobin A2B2) • HbF (Foetal haemoglobin (A2G2) Thalaessaemia is due to an autosomal recessively inherited gene mutation. Most common in the Mediterranean, Middle east and Asia. 4 genes produce the production of alpha, 2 genes produce the production of beta Severity of the disease is dependent on the genotype. Homo = Severe disease – severe anaemia, jaundice, splenomegaly, bone hypertrophy Hetero = Usually asymptomatic and mildly anaemic. Mx: MMay not require treatment depending on genotype. If symptomatic, transfuse Potential side effect of repeat transfusions? The Peer Teaching Society is not liable for false or misleading information…

  37. Sickle Cell • AR disease due to HbS mutation. Commoner in Afro-Carribean. • Infective trigger? Advantage to being hetrozygote? • HbS has a tendency to become rigid and sickle when deoxygenated. Precipitated by infection, dehydration, hypoxia and cold • Crises: Haemolytic, Occlusive, Aplastic and Sequesteration • Symptoms: Bone/pleuritic/abdo pain; Priapism; Avascular necrosis; Priapism The Peer Teaching Society is not liable for false or misleading information…

  38. Sickle Cell • Ix: Film (reticulocytes), Hb electrophoresis, G+S+crossmatch • Mx: • Supportive: Aggressive analgesia (i.e. opiates), treat underlying cause (e.g. antibiotics); Fluids; Folic acid; Transfuse with falling Hb • Chronic: Hydroxycarbamide (for freq crises) • If hyposplenic: Penicillin LY, Pneumococcal and meningococcal vaccination • Cx: Gallstones, leg ulcers, AVN of femoral head, splenic infarction, CKD The Peer Teaching Society is not liable for false or misleading information…

  39. Chris’s case #2 A 47-year-old teacher complains of difficulty maintaining her concentration at work teaching secondary school children. She states that over the last four months she has become increasingly tired and easily fatigued. She has noticed it has become more difficult for her to lift books, rise from her chair and she has also noticed a tingling sensation in her fingers. Examination shows a positive Babinski sign and absent reflexes. A blood test reveals the following:Haemoglobin 10 g/dLMCV 103 fL What neurological complication has she developed? What other tests would you like to order? What is your diagnosis? The Peer Teaching Society is not liable for false or misleading information…

  40. B12 deficiency Weakness due to b12 deficiency leading to subacute degeneration of the cord Causes of b12 deficiency Pernicious anaemia, Malabsorption, Dietary The Peer Teaching Society is not liable for false or misleading information…

  41. PernicousAnaemia • Absorption of vit B12 in terminal ileum, needs intrinsic factor from gastric parietal cells • Pernicious anaemia is an autoimmune condtion here antibodies are produced agaist parietal cells – associated with oither autoimmune conditions e.g. Addison’s • Symptoms: Anaemia, paraesthesia, numbness (legs> hands), cognitive changes, altered vision, Sore mouth (glossitis, angular cheliosis) • Ix: FBC (Raised MCV), Reduced b12, reduced platelets, CHECK FOLATE, IF antibodies, Shilling’s test, Film (Hypersegmented polymorphs and Megaloblasts) • Tx- IM hydroxocobalamin The Peer Teaching Society is not liable for false or misleading information…

  42. Folate Deficency • Found in green veg, liver, nuts and yeast. • CONTRAST to b12 – short term stores (weeks) and absorbed in the upper SI • Causes: Dietary, malabsorption, Increased req (e.g. pregnancy); Folate antagonists • Ix: Low folate, low Hb, Film (Hypersegmented polymorphs and Megaloblasts), ?malabsorption • Mx: Folic acid supplements The Peer Teaching Society is not liable for false or misleading information…

  43. HaemoltyicAnaemia • Causes: • Congential: Heriditary spherocytosis/ elliptocytois, Thallasaemia, Sickle Cell, G6PD • Acquired: Autoimmune haemolytic anaemia, Microangiopathic haemolytic anaemia • Si/Sy: • Pallor, Jaunidce; Splenomegaly • Ix: ↑Unconjugated bilirubin, ↑LDH, Coombs test +ve, Reduced reticulocytes The Peer Teaching Society is not liable for false or misleading information…

  44. Coagulation Disorders • Causes: • Congenital (haemophilia, VW disease) • Acquired (anticoagulants, liver disease, Vit K deficiency) The Peer Teaching Society is not liable for false or misleading information…

  45. Relevant blood tests PT – marker of the extrinsic pathway: 912 seconds APTT – marker of the intrinsic pathway: 2229 seconds Von Willebrand Factor (absent in von Willebrand disease) Platelets – usually 150-400 x109/L Bleeding time – objective measure of how long it takes the patient to coagulate (not used commonly) The Peer Teaching Society is not liable for false or misleading information…

  46. Anti-coagulation Warfarin Mech: Antagonises vit K dependant clotting factors – 2,7,9,10. Increases INR to therapeutic level. Requires regular monitoring Potential for overcoagulation/ reaction with other medication. If INR raised, withhold until reduced, consider giving vit K. If bleeding consider replacing missing factors and FFP Heparin Mech: Inactivates factor Xa Risk of bleeding and inducing thrombocytopenia Revers: Omit heparin and give protamine sulphate The Peer Teaching Society is not liable for false or misleading information…

  47. Hemophilia A+B • X linked-recessive disorder of coagulation. Symptoms are dependent on the level of deficiency • Haemophilia A: Deficiency of factor VIII • Haemophilia B: Deficiency of factor IX • Sy/Si: Haemoarthrosis, secondary arthritis, spontaneous soft tissue bleeds, GI bleed, haematuria • Ix: Raised APTT, Normal PT, Normal vWF, Normal Platelets. CT/USS for suspected bleeds • Mx: • Avoid NSAIDs and IM injections • Minor bleed: Elevate and pressurise • Major bleed: Replace missing factor to help correct clotting factors and improve haemostasis The Peer Teaching Society is not liable for false or misleading information…

  48. Von Willebrand’s Disease Von Willebrand factor acts to prevent factor VIII from destruction Autosomal dominant condtion leading to mucocutanoeus bleeds and easy bruising Ix: FBC; ↑APTT; -PT; ↓vWF; ↑bleeding time Large bleed Mx: Tranexamic acid DDAVP (vasopressin) vWF concentrate Cryoprecipitate FFP The Peer Teaching Society is not liable for false or misleading information…

  49. Chris’s Case #3 A 45-year-old man collapses at home and is brought to accident and emergency. He has a fever at 39.5°C and blood pressure is 90/60 mmHg, although he is in a lucid state. Bruises can be seen on his skin which he remembers being present before hefell. Blood tests show the patient to have a normocytic anaemia with a low platelet count and increased fibrin split products. What is the most likely diagnosis? What has triggered it? The Peer Teaching Society is not liable for false or misleading information…

  50. Disseminated Intravascular Coagulation • Pathological activation of the coagulation cascade  formation of microvascular thrombi and multi organ failure. Consumption of fibrinogen, platelets and clotting factors  haemorrhage • Causes: Sepsis, haematological cancers, eclampsia, anaphylaxis, severe trauma/burns. Severe liver disease • Ix: ↑PT ; ↑APPT; ↓Fibrinogen; ↑FDP; ↓Plt • Mx: Treat underlying; FFP; Cryoprecipitate • Cx: Massive haemorrhage; End organ failure; Death The Peer Teaching Society is not liable for false or misleading information…

More Related