1. Haematology laboratory test result interpretation and an approach to anaemia diagnosis Dr. Andy Hughes Consultant Haematologist

2. Case study 1 25 year old female Cypriot. c/o tiredness -> FBC Hb = 10.5 MCV = 65 (82-96) RBC = 5.5 (3.9-5.0) MCHC = 32 (32-35) RDW = 12 (10-14) 3. Case study 1 Microcytic anaemia Possible diagnoses? Iron deficiency Thalassaemia trait Additional tests? Ferritin 50; iron deficiency unlikely Hb A2 5% - raised Confirms thalassaemia trait 4. Case study 2 70 year old Caucasian male c/o recurrent mouth ulcers Hb = 10 MCV = 105 WCC = 2.1 (>4.0) Neutros = 0.5 (>2.0) Platelets = 120 (>150) 5. Case study 2 Macrocytic anaemia with a pancytopenia Further investigations? B12 = 180 (>240) Serum folate = 5.5 LFTs - normal TSH - normal Retics = 25 (50 makes iron deficiency less likely In early deficiency or with mixed deficiencies MCV may be normal Causes Diet Young and old Malabsorption Coeliac (tTG) Chronic blood loss GIT Uterine UGT 14. Failure to respond to iron Inadequate treatment Dose and/or duration Avoid slow release preparations Continued cause Bleeding Malabsorption Poor compliance Intolerance due to side effects Incorrect diagnosis 15. Parenteral iron Indications: Genuine intolerance Malabsorption Gastric/upper GI surgery Inflammatory bowel disease IM CosmoFer Z-track technique IV Venofer as repeated small volume injections CosmoFer as TDI Problem with allergy/anaphylaxis Avoid if h/o Drug reaction(s) Allergy Asthma 16. Increased Ferritin Infection/inflammation Chronic liver disease; esp. alcohol related Malignancy Repeated transfusions Hereditary haemochromatosis >1000 is risk of organ damage Porphyria Cutanea Tarda Prolonged iron therapy without iron deficiency 17. Case study 3 65 year old Caucasian male. Known stable, mild CLL; no treatment. c/o increasing fatigue and breathlessness. o/e jaundiced. No enlarged lymph nodes or spleen. 18. Case study 3 Initial tests Hb = 8. MCV = 102. WCC = 30 (prev. 15). Lymphs = 25 (prev. 12). Platelets = 300. Bilirubin = 60 (115 Patient may not be anaemic. May be neurological symptoms only, including dementia. Levels can fall in pregnancy. Autoantibody tests are useful (IFA/GPC). Schilling test of limited use. Trial of B12. 28. B12 levels >250 ng/L normal. 4 genuine deficiency unlikely. 120) Methotrexate Azathioprine 31. Case study 4 60 year old Caucasian male. c/o breathlessness. Hb= 9.0. MCV = 88. WCC and platelets normal. 32. Case study 4 Investigations: Haematinics normal. TSH normal. LFTs normal. ESR 30. Creatinine 250. Possible cause of anaemia? 2o to renal impairment Additional tests: EPO level = 15. Ferritin Retics 30 (18.5/HCT >52% Women Hb >16.5/Hct >48% Persistent. Always repeat the FBC. 38. Polycythaemia - causes Primary (PRV/PV) Itching (bath/shower) Splenomegaly Raised WCC/platelets Raised uric acid/gout Secondary Heavy smoking/COPD Oxygen saturation At rest and post exercise Sleep apnoea/obesity h/o snoring Day time sleepiness Renal lesions esp. Ca Abdominal USS 39. Polycythaemia new tests Erythropoietin Low with PRV Raised with: COPD Renal tumours Not always clear cut. JAK2 mutations Janus Kinase Associated with cell signaling pathways Mutations associated with increased cell proliferation ~95% of PRV ~50% PT/MF Normal with other causes of polycythaemia 40. Neutrophilia Infection/inflammation Malignancy Myeloproliferative diseases: PRV/1o Thrombocythaemia/Myelofibrosis Raised Hct or platelets; splenomegaly Steroid treatment Chronic myeloid leukaemia 41. Neutrophila blood films Reactive neutrophilia Chronic myeloid leukaemia 42. Eosinophilia Common Drugs Allergy Asthma; eczema; urticaria Parasitic infection Less common CTDs esp. PAN Some skin diseases: Pemphigus; DH Malignancy: Hodgkins disease Sarcoidosis Eosinophil 43. Case study 5 75 year old Caucasian male Routine FBC Hb =14 WCC =20 Neutros = 5 Lymphs = 15 Platelets = 300 Blood film: Mature lymphocytes Smear cells 44. Case study 5 Likely diagnosis? Chronic lymphatic leukaemia. What physical signs would you look for? Enlarged lymph nodes or spleen. Additional tests Immunoglobulins Direct Antiglobulin Test 2microglobulin Immunophenotyping Cytogenetics Bone marrow -no 45. Lymphocytosis Infections; esp. viral Age of patient Blood film Lymphoproliferative diseases: CLL Age; enlarged lymph nodes or spleen; blood film Lymphomas Hairy cell leukaemia 46. Lymphocytosis blood films (1) Reactive lymphocytes CLL 47. Lymphocytosis blood films (2) Lymphoma cells Hairy cells 48. Case study 6 40 year old Afro- Caribbean male Routine FBC for HT. Hb = 14 WCC = 2.8 Neutros = 1.0 Platelets = 300 Relevant history/exam? Recurrent infection or mouth ulcers no. Drugs Losartan for HT. Rheumatological symptoms no. Enlarged spleen no. Likely diagnosis? Benign ethnic neutropenia. 49. Neutropenia Benign-ethnic (Afro-Caribbean). Infections; esp. viral. ?age. Drugs/recent chemotherapy. Bone marrow disease (Hb; platelets). Megaloblastic anaemia (Hb/MCV). Immune: Autoimmune SLE RA (Feltys syndrome; associated splenomegaly). 50. Lymphopenia SLE/RA HIV Chemotherapy Malignancies eg Hodgkins disease Sarcoidosis 51. Case study 7 35 year old Caucasian female c/o joint pains Hb = 12 WBC = 4 Neutros = 2 Platelets = 80 MPV = 12 No h/o excess bleeding Possible diagnoses: Rheumatological SLE Immune ITP Drugs HIV 52. Thrombocytopenia Isolated: Drugs Autoimmune ITP Immune secondary to: SLE; LPDs. HIV and other immunodeficiency syndromes Ch. Liver disease with portal HT Alcohol (?MCV) Antiphospholipid syndrome Other cytopenias: Megaloblastic anaemias Hb and MCV Bone marrow disease MDS Leukaemias Aplastic anaemia 53. Thrombocytopenia - investigations ANA Antiphospholipid tests: Anticardiolipin antibodies Lupus anticoagulant tests HIV test; esp. in at risk individuals LFTs B12 and folate 54. Thrombocytopenia in pregnancy Gestational Mild 2nd and 3rd trimester Associated with PIH syndromes Autoimmune (ITP) Often seen in 1st trimester HIV 55. Thrombocytosis Reactive: ?recent change Infection/inflammation ESR/CRP Malignancy Iron deficiency/bleeding Post splenectomy Primary (MPDs): Persistent increase 1o Thrombocythaemia PRV Myelofibrosis Enlarged spleen CML Low Hb Raised WCC Splenomegaly 56. Case study 8 70 year Caucasian female c/o back pain FBC - normal U and E normal LFTS - raised globulins 42 Protein electrophoresis showed IgG paraprotein 5 Other Igs (A and M) normal Possible diagnoses: Myeloma? benign? MGUS Further investigations: Urine for BJP - negative X-rays OA changes only Calcium normal Likely diagnosis? MGUS. 57. Raised globulins Often a non-specific reaction to infection or inflammation. Protein electrophoresis usually shows a diffuse increase in gamma globulins. Think of HIV in risk groups. Electrophoresis may show a paraprotein. 58. Protein electrophoresis Paraproteins: Myeloma (IgG or A). Lymphoproliferative diseases (IgM, G or A): NHL Waldenstrms (IgM) CLL Amyloidosis. MGUS. 1 = Normal 2 = Diffuse increase in globulins 3 & 4 = paraproteins 59. Myeloma Vs. MGUS Myeloma New bone pain End organ failure Anaemia Increased creatinine Hypercalcaemia Higher concentration paraprotein Immune paresis Bence Jones protein Lytic lesions on X-rays Typical bone marrow findings MGUS Asymptomatic No end organ failure Low concentration paraprotein No immune paresis No/minimal BJP No skeletal lytic lesions Bone marrow not always necessary 60. Myeloma bone lesions 61. Myeloma bone marrow 62. THANKS! ANY QUESTIONS?