Haematology Update for General Practice Dr Naim Akhtar Consultant Haematologist Barts Health/ Whipps Cross University Hospital 13th November 2013 Haematology Update for General Practice  The use of the laboratory and interpretation of blood tests in common haematological conditions  The Myeloproliferative disorders  Iron Overload  Sickle cell disorders  Thrombophilia & Anticoagulation  Malignant Haematology Normal Ranges          Haemoglobin (Hb) Red cell count (RBC) Haematocrit (Hct) Mean Cell Volume (MCV) Platelet count (PLT) Total White Blood Count (WBC) Neutrophil count Lymphocyte count Erythrocyte Sedimentation Rate (ESR) 115 – 180 g/L 4.7 – 6.1 x 10 /L 0.42 – 0.52 80 – 95 fL 130 – 400 x 10 /L 4 – 11 x 10 /L 2 – 6 x 10 /L 1 – 3 x 10 /L 0 – 20 mm/H Normal blood film Anaemia – MCV as a determinant of cause  Low MCV - iron studies/blood loss/thalassaemia  Normal MCV – chronic disease (CRF, RA, DM, Liver)  High MCV – B12/Folate/alcohol/TFTs/MDS/Retics/ Haemolytic screen direct coomb’s test Initial approach to anaemia       History & examination Hb, MCV Haematinics - B12 & Folate assays - serum Fe/TIBC & Ferritin Reticulocyte count ESR Miscellaneous (FOBs, TFTs, Biochem etc) Macrocytic anaemia WBC changes  Blood film essential (machine differential is unreliable)  Reactive secondary to infection/inflammation  MPD or inderterminant  Leukaemia – usually obvious, unless pancytopenic WBC changes       Neutropenia (Infections, Drug-induced, Racial, myelodysplasia) – concern < 1.0 or persistent Lymphopenia (Infections, HIV) Neutrophilia (Infections, Inflammation, chronic myeloproliferative disorders) Lymphocytosis (Infections, Leukaemia) Eosinophilia (allergy, drugs, asthma) Monocytosis (Infections, myelodysplasia) Reactive lymphs Platelet changes  Factitious (clots in tube/ blood film, difficult venepuncture)  Thrombocytopenia  Thrombocytosis (Reactive, Primary)  Functional platelet disorders (inherited and acquired) Platelet changes  Thrombocytopenia (Immune, consumption, bone marrow disorders) concern < 50  Thrombocytosis (Reactive, myeloproliferative disorder) concern >600 & persistent  Platelet function defects (Aspirin, hereditary, renal, liver disease) The Myeloproliferative Disorders (MPDs aka MPNs): Recent Advances Essential thrombocythaemia Overview of the MPDs BCR-ABL mutation – CML – TKIs  BCR-ABL negative MPDs (PRV, ET, IMF)  JAK-2 V617F mutation - >95% PRV - 50-60% ET, IMF - prognostic value - indication for cytoreductive therapy - excludes secondary/reactive states  Other mutations (e.g. MPL)  Iron Overload Type 1 haemochromatosis       Most common genetic condition (AR) in Northern Europeans 1:8 carriers, 1:200 homozygous C282Y mutation of HFE gene. >95% C282Y & H63D mutations. Chronic iron accumulation in homozygotes lead to tissue damage (cirrhosis, diabetes, hypogonadism, arthritis) Ferritin > 1000 associated with hepatic cirrhosis Age 40-60 Clinical penetrance is low HFE & iron status  Clinical suspicion or incidental finding  Raised transferrin saturation (>50-55%)  Raised ferritin (>200-300 mcg/l)  Liver biopsy to assess tissue damage  Phlebotomy (weekly to normal ferritin)  Family testing (1st degree)  Population screening Type 2 or secondary iron overload  Chronic transfusion therapy (e.g. Thalassaemia major, myelodysplasia)  Iron overload & organ damage  Ferritin > 1000  IV & SC iron chelation (desferrioxamine)  Deferiprone – second line  Deferasirox – first & second line Sickle cell disorders Sickle cell disease  Chronic haemolytic anaemia  At risk population  Genotypes (SS, SC, S-thal, AS trait)  Types of anaemia  Acute painful crises  Infections & asplenia  Common complications Sickle cell disorders: Recent recommendations  Universal screening  Pain relief and symptom control  Cranial doppler scanning & stroke prevention  Hydroxycarbamide for severe/recurrent sickle cell crises  Blood transfusion & exchange  Bone marrow transplantation Thrombosis & Anticoagulation Inherited thrombophilia  Heritable - ATIII, PC, PS - FVL, PTG 20210A  Acquired - Antiphospholipid syndromes  Mixed - High Clotting Factors (VIII, XI, X) - Hyperhomocyteinaemia Prevalence of heritable thrombophilias      ATIII PC PS FVL PTG pop. 0.02% 0.2% ? 2-15% 1-4% VTE 0.5-1% 3.0% 1.0% 20-50% 6% NB: Pregnancy 1:1000 risk of VTE VTE preg. 4-8% 2% ? 8% 9% Acquired VTE (venous thrombo-embolism)  Inevitable - age, pregnancy, immobility, dehydration  Iatrogenic - post-op., indwelling devices, OCP, chemo.  Disease-related - APS, Cancer, Inflammatory, IV drug abuse, Haematological (PNH, TTP, SCD) APS (The antiphospholipid syndromes)  Clinical - arterial, venous or microvascular VTE - pregnancy complications (IUD, miscarriages, pre/eclampsia & prematurity  Laboratory - Lupus AC - IgG and/or IgM aCL high titres Anticoagulation         Low molecular weight heparins (LMWH) Oral anticoagulation - Warfarin Thrombo-prophylaxis with LMWH or UH Traditional Hospital clinics POCT & self-testing Reversal & bleeding Risks & benefits Direct Anti-IIa & Xa inhibitors Direct thrombin inhibitor        Dabigatran etexilate Oral, renal excretion, limited license 220 or 110 mg once daily Non-inferior to enoxaparin in prevention of VTE in knee/hip surgery, Warfarin in non-valvular AF No excess bleeding or adverse events No specific antidote Cost comparable to enoxaparin (LMWH) Direct anti-Xa inhibitors  Rivaroxaban in AF (20 mg daily) and DVT/ PE (15 mg BD x 3 weeks, then 20 mg daily)  Rivaroxaban dual mode of excretion  Alternative to conventional heparin/ Warfarin for treatment of VTE  Apixaban licensed for AF, less incidence of GI bleeding Malignant Haematology Urgent referrals        2 week cancer target referral form Abnormal blood results (e.g. lymphocytosis, pancytopenia, neutropenia) Acute & Chronic Leukaemia Lymphadenopathy Splenomegaly Iron deficiency & weight loss Miscellaneous (e.g. drenching night sweats, abnormal CT or MRI scans) Questions? Thank you for your attention