1. Thrombocytopenia Dr S W Bokhari Consultant Haematologist University Hospital Coventry and Warwickshire

2. Thrombocytopenia You are the Surgical HO asked to clerk patient on ward pre- operatively prior to hernia repair. You notice from results on CRRS that his platelet count one week earlier was 25. No previous results. How do you approach this problem?

3. Repeat FBC Repeat FBC Hb 13g/dL WCC 8 Neuts 2.5 Plts 28 MCV 102 Ask for blood film to be reviewed Ask for blood film to be reviewed Film comment – confirmed thrombocytopenia, normal platelet morphology; mild macrocytosis; no other abnormal features Inform surgeons/theatres etc Inform surgeons/theatres etc

4. Peripheral blood film

5. Platelet clumping

6. History 40 year old man Symptoms: Symptoms: Bleeding history – severity and duration Recent illness – including infections esp. viral Recent illness – including infections esp. viral Patient had noticed easy bruising for previous 2 months. Fit and well with no recent illness

7. Mucosal bleeding

8. Purpura

9. Past Medical History Infections – bacterial, viral, fungal Infections – bacterial, viral, fungal Autoimmune disease Autoimmune disease Liver disease Liver disease Malignancy Malignancy Occasional backpain Road traffic accident 5 years ago following which he received blood transfusion

10. Family History Congenital causes of thrombocytopenia Congenital causes of thrombocytopenia Autoimmune disease Autoimmune disease Mother – IDDM Sister recently diagnosed with SLE

11. Drug History Long list to consider! Long list to consider!-immune-mediated -direct effect on BM or MK Alcohol intake Alcohol intake Takes diclofenac for backpain 30 units alcohol per week – spirits Smokes 15/day

12. Social History Occupation - ? Exposure to toxic agents Occupation - ? Exposure to toxic agents Dietary history Dietary history Recent travel abroad – infections Recent travel abroad – infections Risk factors for HIV Risk factors for HIV Recently made redundant having previously worked in motor industry No recent travel abroad No risk factors for HIV

13. Examination Bleeding/bruising Bleeding/bruising Anaemia Anaemia Clubbing/jaundice (other features of CLD) Clubbing/jaundice (other features of CLD) Lymphadenopathy Lymphadenopathy Signs of malignancy Signs of malignancy Hepatomegaly Hepatomegaly Splenomegaly Splenomegaly Features associated with congenital causes esp. Fanconi Features associated with congenital causes esp. Fanconianaemia

14. Bruising over arms and legs ? Yellow sclera Liver palpable 3cm No other findings

15. Investigations FBC FBC Pancytopenia or isolated thrombocytopenia MCV Blood film Blood film Confirm thrombocytopenia Platelet size and morphology Red cell fragments Red cell abnormalities e.g. target cells WBC features

16. Giant platelets

17. Red cell fragments

18. Target cells

19. Hypersegmented neutrophil

20. Hb 13g/dL WCC 5 Neuts 2.0 Plts 28 MCV 102 Target cells and stomatocytes

21. Renal function Renal function Liver function Liver function B12 and folate B12 and folate Full clotting screen Full clotting screen Normal renal function AST 160 Alk phos 170 ALT 130 Bili 60 γGT 100 B12 110 Folate 1.4 PT ratio 1.6 APTT ratio 1.4 Normal fibrinogen and TT

22. Autoantibody screen + specific autoantibodies as indicated Autoantibody screen + specific autoantibodies as indicated Antiphospholipid antibodies Antiphospholipid antibodies Lupus anticoagulant Anticardiolipin antibodies Autoantibodies screen negative Antiphospholipid antibodies positive

23. Virology testing Virology testing EBV, CMV, toxoplasma Hep B, C HIV Hepatitis C positive Presumed secondary to blood transfusion

24. Causes of thrombocytopenia Failure of production Failure of production Increased consumption/destruction Increased consumption/destruction Abnormal pooling - splenomegaly Abnormal pooling - splenomegaly

25. Failure of production Congenital: Congenital: Fanconi anaemia, TAR (thrombocytopenia with absent radii), Wiskott-Aldrich syndrome, Bernard-Soulier synd.*, May-Hegglin anomaly*, Alport synd. variant*, Grey platelet synd.* Acquired: – specific thrombocytopenia Acquired: – specific thrombocytopenia Infection esp. viral Nutritional deficiency – B12/folate Toxic effect of drugs (more often immune) or alcohol

26. Failure of production Acquired: – as part of bone marrow failure Acquired: – as part of bone marrow failure Drugs including chemotherapy Radiotherapy Marrow infiltration – malignant/non-malignant Aplastic anaemia

27. Bone marrow aspirate

28. Bone marrow trephine

29. Increased destruction of platelets Immune ImmuneIdiopathic: ITP (acute and chronic) Secondary: Autoimmune disease e.g. SLE Infections e.g. HIV, Hepatitis C Drugs e.g. heparin (HIT), quinine, quinidine, gold salts Lymphoproliferative disease e.g. CLL Neonatal alloimmune thrombocytopenia Post-transfusion purpura

30. Increased destruction of platelets Non-immune Non-immune Microangiopathic haemolytic anaemia (MAHA) DICHUS TTP – idiopathic or 2º e.g. pregnancy, infection, metastatic carcinoma, drugs, BMT, AI disease Pregnancy related Pregnancy related Gestational thrombocytopenia PreeclampsiaHELLP

31. Management Few spontaneous bleeding problems if plts > 30 Few spontaneous bleeding problems if plts > 30Unless: Abnormal platelet function Associated coagulopathy In general patients need treatment if symptomatic or increased risk of bleeding e.g. peri/post-operatively, trauma, obstetric In general patients need treatment if symptomatic or increased risk of bleeding e.g. peri/post-operatively, trauma, obstetric In general would want platelets > 50 for minor op and >80/100 for major op. In general would want platelets > 50 for minor op and >80/100 for major op. May need to transfuse plts if count higher but abnormal function May need to transfuse plts if count higher but abnormal function

32. Management May need bone marrow to determine whether cause of thrombocytopenia is failure of production or increased destruction May need bone marrow to determine whether cause of thrombocytopenia is failure of production or increased destruction Stop any possible implicated drugs Stop any possible implicated drugs In general if failure of production: In general if failure of production: Platelet transfusions Treat underlying cause e.g. B12/folate replacement

33. Management In general if increased destruction: In general if increased destruction: Avoid platelet transfusions as these are often ineffective and can make clinical situation worse e.g. TTP, HIT Exception - DIC May be required if life-threatening bleeding e.g. ITP Treat underlying cause e.g. CLL ITP: Immunosuppression – steroids, IVIG, other immunosuppressive agents Splenectomy

34. Management TTP-HUS may require plasma exchange/FFP NAIT/PTP may require HPA1 A neg plts