1 West Herts GP Consultant Forum (08/09/2010) Haematological Irritations Dr Anna Wood

2 Topics for discussion Polycythaemic indices Neutropaenia Lymphocytosis Platelet clumping Immunoglobulins Thrombophilia

3 Normal indices Female Hb12-15g/dl Hct Rbc x Male Hb13-16g/dl Hct Rbc x Polycythaemic indices HCT > 0.48HCT > 0.52

4 Polycythaemic indices When does it matter? What are the consequences? When to investigate and how far? When to refer?

5 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

6 Definition and Classification of Polycythaemia Hct > 0.52 men and > 0.48 women True Polycythaemia Primary (MPD) Secondary Congenital eg high o 2 affinity Hb Erythropoetin- driven Drugs eg androgens Post renal transplant Relative Polycythaemia Reduction in plasma volume but no increase in red cell mass

7 2) What are the consequences? A Primary High risk VTE and stroke Pseudo/ApparentUnknown risk of VTE SecondaryLess risk VTE BUnderlying pathology

8 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

9 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

10 Case 1 82 year old lady 3 episodes VTE and stroke/ now on indefinite warfarin GP referral with Hb 17.8 g/dl HCT WCC 7.1 x109/L Platelets 268 x 109/L JAK 2 V617 mutation positive Primary proliferative polycythaemia

11 Case 2 59 year old male/ heavy smoker Went to GP as tired Progressively abnormal Hb and HCT 2007Hb 16.2 g/dl HCT Hb 18.3 g/dl HCT 0.53 Haematology referral Epo levels 40iu/l (5-25) Renal cancer

12 Mild Neutropaenia Facts Normal Neutrophil count1.9 – 7.0 x109/L Ethnic variant0.8 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

13 Importance of blood film

14 Neutropaenia What are the consequences? Of neutropaenia< 0.5 x 109/L Of underlying condition

15 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

16 Lymphocytosis Normal x109/L Age Causes Clinical context

17 Causes isolated lymphocytosis in elderly CLL Low grade lymphoma Monoclonal B-cell Lymphocytosis (MBL) Splenectomised Smoking Endocrine

18 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

19 Case provided (CLL) 76 year old lady, IHD on various medications Lymphocytes 6 x 109/L How often to monitor? When to refer?

20 How often to monitor? First must request blood film. If no lymphadenopathy, organomegaly, B symptoms and otherwise normal blood count6 monthly and there is an ‘assumption’of CLL

21 CLL blood film

22 Other lymphoproliferative disorder

23 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

24 Importance of Red blood cell count Raised RBC with Microcytosis Thalassaemia trait Hb 9 g/dl MCV 62 RBC 6.0 x 109/L Iron deficient primary polycythaemia Hb 16 g/dl MCV 77 RBC 5 x 109/L Compare Primary polycythaemia Hb 20 g/dl MCV 90 x 109/l RBC 6 x 109/L

25 Platelet clumping In vitro phenomenon Of no clinical consequence Lab should delete platelet count Citrated sample sometimes helps

26 Platelet clumping

27 Polyclonal increase immunoglobulins Connective tissue disease Chronic infections (HIV TB) Non haematological malignancies

28 Thrombophilia Young girl with family history VTE Prior to COCP Should we test for thrombophilia?

29 Why do thrombophilia tests? Predict the rate of recurrence in a patient with VTE Predict the risk of 1 st VTE in family member

30 1) Predicting rate of recurrence VTE Recurrence rate15-20%First 2 years Post opOther provoked Spontaneous Minimal10%20% No additional risk factor for recurrence if thrombophilia Single biggest risk factor for recurrence VTE is VTE

31 2) Prediction VTE in unselected cases Background incidence VTE women childbearing age 1 per 10,000 per year COCP3x risk COCP + Factor V Leiden30x risk Screening all women not economically viable

32 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

33 Testing females prior COCP with family history BSCH guidelines 2010 First degree relative VTE Tested positive Tested negative Not tested Consider an alternative contraception or transdermal HRT Thrombophilia testing not recommended

34 Thank you Any Questions