Thrombocytopenia Dr S W Bokhari Consultant Haematologist

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

4. Peripheral blood film

5. Platelet clumping

6. History 40 year old man • Symptoms: Bleeding history – severity and duration • 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 • Autoimmune disease • Liver disease • Malignancy Occasional backpain Road traffic accident 5 years ago following which he received blood transfusion

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

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

12. Social History • Occupation - ? Exposure to toxic agents • Dietary history • Recent travel abroad – infections • 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 • Anaemia • Clubbing/jaundice (other features of CLD) • Lymphadenopathy • Signs of malignancy • Hepatomegaly • Splenomegaly • Features associated with congenital causes esp. Fanconi anaemia

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

15. Investigations • FBC Pancytopenia or isolated thrombocytopenia MCV • 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 • Liver function • B12 and folate • 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 • Antiphospholipid antibodies Lupus anticoagulant Anticardiolipin antibodies Autoantibodies screen negative Antiphospholipid antibodies positive

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

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

25. Failure of production • 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 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 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 Idiopathic: 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 Microangiopathic haemolytic anaemia (MAHA) DIC HUS TTP – idiopathic or 2º e.g. pregnancy, infection, metastatic carcinoma, drugs, BMT, AI disease • Pregnancy related Gestational thrombocytopenia Preeclampsia HELLP

31. Management • Few spontaneous bleeding problems if plts > 30 Unless: 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 would want platelets > 50 for minor op and >80/100 for major op. • 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 • Stop any possible implicated drugs • In general if failure of production: Platelet transfusions Treat underlying cause e.g. B12/folate replacement

33. Management • 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 HPA1A neg plts