West Herts GP Consultant Forum (08/09/2010)

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. Female Hb 12-15g/dl Hct 0.36-0.44 Rbc 3.86-4.9 x Male Hb 13-16g/dl Hct 0.38-0.49 Rbc 4.15-5.15 x Normal indices 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. Age Persistence or progression of abnormality VTE Arterial disease Abdominal mass Family history Drugs Smoker Alcohol Cyanotic heart disease Chronic respiratory disease Hypertension When does it matter?Clinical Context

6. Definition and Classification of PolycythaemiaHct > 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

7. 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

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 0.549 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 • 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

12. 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

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 1.2 - 3.5x109/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 count 6 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. 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 Importance of Red blood cell countRaised RBC with Microcytosis

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 1st VTE in family member

30. 1) Predicting rate of recurrence VTE • Recurrence rate 15-20% First 2 years Post op Other provoked Spontaneous Minimal 10% 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 • COCP 3x risk • COCP + Factor V Leiden 30x risk • Screening all women not economically viable

32. 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 3) Selective screening of asymptomatic relatives

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

34. Thank youAny Questions