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West Herts GP Consultant Forum (08/09/2010) Haematological Irritations Dr Anna Wood 1 Topics for discussion Polycythaemic indices Neutropaenia Lymphocytosis Platelet clumping Immunoglobulins Thrombophilia 2 Normal indices Female Hb 12-15g/dl Hct 0.36-0.44 Rbc 3.86-4.9 x Hb Hct Rbc Male 13-16g/dl 0.38-0.49 4.15-5.15 x Polycythaemic indices HCT > 0.48 HCT > 0.52 3 Polycythaemic indices When does it matter? What are the consequences? When to investigate and how far? When to refer? 4 1) When does it matter? Clinical Context Age Persistence or progression of abnormality VTE Arterial disease Abdominal mass Family history Drugs Smoker Alcohol Cyanotic heart disease Chronic respiratory disease Hypertension 5 Definition and Classification of Polycythaemia Hct > 0.52 men and > 0.48 women True Polycythaemia Primary (MPD) Secondary Congenital eg high o2 affinity Hb Erythropoetin- driven Drugs eg androgens Post renal transplant Relative Polycythaemia Reduction in plasma volume but no increase in red cell mass 6 2) What are the consequences? A Primary High risk VTE and stroke Pseudo/Apparent Unknown risk of VTE Secondary Less risk VTE B Underlying pathology 7 3) When to investigate and how far? History and Examination If no obvious cause repeat (uncuffed) Age if young (?) do renal / abdominal ultrasound Urate levels (a) well hydrated 87 year old man, non smoker (b) 37 year old female, non smoker, asthmatic on ventolin, normal renal USS 8 4) When to refer? No obvious cause (pseudo) and persistence of abnormality If white cells and platelets elevated as well If obvious cause AND VTE/ Arterial history If there is obvious cause but concern re necessity for venesection 9 Case 1 82 year old lady 3 episodes VTE and stroke/ now on indefinite warfarin GP referral with Hb 17.8 g/dl HCT 0.549 WCC 7.1 x109/L Platelets 268 x 109/L JAK 2 V617 mutation positive Primary proliferative polycythaemia 10 Case 2 59 year old male/ heavy smoker Went to GP as tired Progressively abnormal Hb and HCT 2007 Hb 16.2 g/dl HCT 0.47 2009 Hb 18.3 g/dl HCT 0.53 Haematology referral Epo levels 40iu/l (5-25) Renal cancer 11 Mild Neutropaenia Facts Normal Neutrophil count 1.9 – 7.0 x109/L Ethnic variant 0.8 x 109/L When does it matter? Clinical context ? Recent acute/ severe viral infection Drugs Other abnormal haematological indices History of recurrent bacterial infections Disease associations eg SLE Degree of neutropaenia Blood film appearance 12 Importance of blood film 13 Neutropaenia What are the consequences? Of neutropaenia < 0.5 x 109/L Of underlying condition 14 Case provided 68 year old man of Asian origin, negative viral screen, on no medication, well. Neutrophils 1.16 x 109/L How often should this be monitored? Request blood film and if normal recheck in 3-4 months 15 Lymphocytosis Normal 1.2 - 3.5x109/L Age Causes Clinical context 16 Causes isolated lymphocytosis in elderly CLL Low grade lymphoma Monoclonal B-cell Lymphocytosis (MBL) Splenectomised Smoking Endocrine 17 CLL Diagnosis of lymphocytes > 5 x109/L Median age 72 Stage A accounts for 80% cases Outcome for stage A 50% stable and never require treatment 50% progress and require treatment Median survival 9 years 20% Stage B and C require treatment 18 Case provided (CLL) 76 year old lady, IHD on various medications Lymphocytes 6 x 109/L How often to monitor? When to refer? 19 How often to monitor? First must request blood film. If no lymphadenopathy, organomegaly, B symptoms and otherwise normal blood count 6 monthly and there is an ‘assumption’of CLL 20 CLL blood film 21 Other lymphoproliferative disorder 22 When to refer If rapid rise in lymphocytes (LDT < 6 months) If at diagnosis presence of ‘B’ symptoms, hepatosplenomegaly or additional abnormality in blood count Patient choice ie would like a substantive diagnosis Blood film suggestive of other low grade lymphoproliferative disorder. Initial Lymphocytes > 30 x 109/L 23 Importance of Red blood cell count Raised RBC with Microcytosis Iron deficient primary Thalassaemia trait polycythaemia Hb 9 g/dl MCV 62 RBC 6.0 Hb 16 g/dl MCV 77 RBC 5 x x 109/L 109/L Compare Primary polycythaemia Hb 20 g/dl MCV 90 x 109/l RBC 6 x 109/L 24 Platelet clumping In vitro phenomenon Of no clinical consequence Lab should delete platelet count Citrated sample sometimes helps 25 Platelet clumping 26 Polyclonal increase immunoglobulins Connective tissue disease Chronic infections (HIV TB) Non haematological malignancies 27 Thrombophilia Young girl with family history VTE Prior to COCP Should we test for thrombophilia? 28 Why do thrombophilia tests? Predict the rate of recurrence in a patient with VTE Predict the risk of 1st VTE in family member 29 1) Predicting rate of recurrence VTE Recurrence rate Post op Minimal 15-20% First 2 years Other provoked Spontaneous 10% 20% No additional risk factor for recurrence if thrombophilia Single biggest risk factor for recurrence VTE is VTE 30 2) Prediction VTE in unselected cases Background incidence VTE women childbearing age 1 per 10,000 per year COCP 3x risk COCP + Factor V Leiden 30x risk Screening all women not economically viable 31 3) Selective screening of asymptomatic relatives Thrombotic family Defect identified Risk VTE asymptomatic family member is UNCERTAIN unless HIGH RISK antithrombin deficiency Protein C /S deficiency Thrombotic family Defect not identified Risk VTE asymptomatic family member is UNCERTAIN False reassurance 32 Testing females prior COCP with family history BSCH guidelines 2010 First degree relative VTE Tested positive Tested negative Not tested Thrombophilia testing not recommended Consider an alternative contraception or transdermal HRT 33 Thank you Any Questions 34