1. Rheumatology Complex Case Discussion session
Medical Education Centre
Southend University Hospital
NHS Foundation Trust
14th February 2017
Dr Amin Islam MB MRCP UK, FRCPath UK
Consultant Haematologist

3. Reviewed in haematology clinic 7/9/16
Problem List
Thrombocytopenia ?cause
Neutropenia resolved
Anaemia (? Anaemia of chronic disease ACD)

4. Past Medical History
Sjogren's disease, 2010 but long H/O dry eyes 15 years back
Guillain-Barre syndrome with full recovery, 2010
Raynaud’s
Stable nodular, right thyroid lobe, 2013
Under investigation by urology team for microscopic haematuria

5. Medication
No know drugs allergies
intermittent natural tear eye drop

6. History and examinations
First noticed some bruising in lower limbs in July
Has progressively increased with time
Apart from bruising on legs had 2 episodes of blood spots on pillow
Had one episode of pink-tinged sputum earlier this week
Does not report any gum bleeding, blood blisters or an other mucosal bleeds.
No B symptoms
On examination today there was no lymphadenopathy or organomegaly.

7. Blood count: 06/09/16 Hb102 , MCV 91.7 WCC 2.9 Neut 1.87 Plt 35
Ferritin/B12/Folate - normal
Total protein 94 Globulin 53 (previously investigated, no paraprotein)
Normal bone profile.
UES: normal
Polyclonally raised immunoglobulin's

8. Plans and Follow up
Explained that we are investigating her thrombocytopenia to look for-
Either a bone marrow disorder or an immune mediated process.
As symptoms are currently bruising, she is fine to go away on her holiday to France tomorrow return and have a bone marrow test on 20th September, 2016
To be seen back in clinic in 6 weeks' time with the results of the investigations.

9. HB trend

10. Neutrophils trend

11. PLT trend

12. Further tests done Borderline B12 deficiency corrected orally
Immunoglobulins: polyclonally raised
BJP :Negative
SFLC ratio: Normal
DAT: Negative
Complement C g/L ( )
Complement C4 * 0.10 g/L ( )
TSH mu/L
Free T pmol/L

13. Bone marrow tests

14. Bone marrow aspirate flow

15. MRI, marrow signal changes, 2010
Cause?

16. ANTI DS DNA (EIA)
Anti ds DNA (EIA) * 14.0 IU/mL
ENA PROFILE
Anti RNP Not Tested.
Anti RNP/Sm Negative
Anti Sm Negative
Anti SSa (Ro60) Positive
Anti Ro Positive
Anti SSb (La) Positive
Anti Scl Negative
Anti Centromere B Negative
Anti Jo Negative

17. Pernicious anaemia and Coeliac screen Negative
TPMT activity 81 Normal
CARDIOLIPIN ANTIBODIES
Anti cardiolipin (IgG) GPLU/mL
Anti cardiolipin (IgM) MPLU/mL
Virology : Negative

18. 22nd September rheumatology clinic

19. 7th October 2016 PLT 16 Prednisolone 40 mg started
19th October 2 weeks on prednisolone
PLT 18
Prednisolone increased to 60 mg

20. 15th November 2016

21. Admitted 1/12/16
Admitted with a platelet count of 7 and a 2 day history of epistaxis.
No recent symptoms suggestive of infection. This is on a background of newly diagnosed ITP/?lupus cytopenia
Not responding to prednisolone. She has recently been started on azathioprine (completed 2 weeks at admission).
Admitted for platelet transfusion and IV Immunoglobulins. .

22. platelet count increased to 22 after 24 hours, however, Hb had dropped further and received 1 unit of blood transfusion
platelets were hours after immunoglobulin treatment.
Initiated eltrombopag 25 mg OD

23. Haematology review 21st December 2016
No bleeding
Tapering prednisolone to 5mg
Still on AZATHIOPRINE 75mg
Eltrombopag 50mg for 2 weeks
PLT 10
Discussed option of Rituximab

24. 5th January 2016 PLT 7, HB 77 Admitted for 1st dose of Rituxamab 1gm
Had 2 units of RCC
Eltrombopag continued
AZATHIOPRINE STOPPED

25. Haematology 11th January 2016
PLT 8, HB 87, wcc 1.5, neut 0.82, lymp .70
Eltrombopag 50 mg continued
Tranexamic Acid continued

26. 19th January 2017 HB 66 , WCC* 1.8 , neut 0.87, PLT 9
Had 1 pool PLT, 2 RCC
2nd dose of RITUXMAB 1g

27. 1st February 2017 PLT 6, HB 79, WCC 3.4 Neut 2.39, lymp 0.75
Nose bleeding
Transfused 1 pool platelets
Long discussion
Next line o try Romoplostin (SC TPO agonist)
Response 15% may be
Wait few more weeks?
?delay response from Rituximab
Second opinion?

28. 9th February 2017

29. 10th February 2017 Reviewed at UCLH Under went second marrow
Repeat re staging bloods
Impression
Likely to be bone marrow failure secondary to multiple antibodies or strong immune destruction

30. What next? And ideas ITP most unlikely here
Peripheral destruction Secondary to multiple antibodies
But LOW HB with DAT negative
Bone marrow failure?
But her marrow was hyperactive 5 months ago
Might needs combinations of drugs?
MMF/Cyclophospahmide/Vincristine?
Pasmapheresis?
ASCT?
CT CNAP?
TCR to exclude T Cell lymphoma?
PNH screen?

31. Learning point
Immune cytopenia can be frightening for patient and the physicians
Only in refractory ITP with bleeding mortality is about 30 % yearly
Every effort should be taken to reach a diagnosis
Try combinations
Ask a friend early