Thrombocytopaenia in Pregnancy

1. Thrombocytopaenia in Pregnancy Dr Guan Yong Khee Hospital Melaka

2. Platelets Normal Platelet Giant Platelet Diameter of 1 – 4 μm Cell volume of 2 to 20 fL Young platelets being larger than the older ones No cell nucleus but has residual mRNA from the megakaryocytes

3. Approximately 70 to 80 % of platelets circulate in the blood 20 to 30 % are stored in the spleen Decomposition of platelets takes place in the spleen and partly in the liver Average life span is 5 to 12 days : mean 7 days

4. Normal Platelet Count What is the normal platelet count? ? 150-450 x 109/L ?150-300 x 109/L Are there racial differences? Western Vs Asian? Malays Vs Chinese?

5. Possible inaccuracies in platelet count • Methods of platelet counting • Separation by cell volume – the impedance measurement principle  problematic if platelet sizes are large or there are RBC fragmentations • RNA staining and flow cytometry(Optical method) Might only be available in some higher end analysers • Separation by detection of the membrane receptors CD61 and CD41 complicated and very expensive

6. What is thrombocytopaenia? Conventionally <150 x 109/L Might be more reasonable to consider it < 100x 109/L Should be confirmed with a peripheral blood film

7. Thrombocytopaenia • What is the minimum platelet number required for normal haemostasis? • Some studies say 5/mcl • Threshold for transfusion • If febrile, transfuse if platelets < 20/mcl • If afebrile, transfuse if platelets < 10/mcl • If bleeding, transfuse if < 50 or < 100(if CNS bleed)

8. Thrombocytopaenia • Bleeding might not be due to low platelet itself only • Usually must rule out other causes of bleeding • Concomitant peptic ulcer disease? Bladder pathology? Cervix or endometrial pathology?

9. Thrombocytopaenia • Problems with platelet transfusions • 1 random unit usually rises the platelet count by about 10/mcl • 1 apheresis unit usually rises the platelet count by 40-60/mcl • Platelet lifespan is short (7-10 days) • Transfused platelet’s lifespan is even shorter (1-2 days) • Transfusion might lead to platelet refractoriness

10. Thrombocytopaenia • Is there a threshold of platelet count to do a BMA? • No • However, I might want to transfuse platelets if it is < 20 to avoid a big haematoma if adequate pressure is not applied long enough post BMA at the BMA site

11. Thrombocytopaenia Other considerations • Low platelet is usually the earliest sign of DIC • Platelets numbers might be underestimated in TTP/ MAHA picture/ increase RBC fragmentation in certains Acute Leukaemias • Possible to be ITP? Unlikely if there is pancytopaenia

12. Diagnosis • FBP • BMA and Trephine biopsy and other investigations • Immunophenotyping • Cytogenetics/ FISH • Molecular/ PCR

13. Diagnosis Extremely important to guide further treatment Transfusing without investigating is like filling up a bucket which is leaking

14. Diagnosis • Possible diagnosis not to be missed • Aplastic Anaemia – Transplant emergency • Acute Leukaemias - ?APML, ?ALL, ?AML M7 • Myelodysplastic Syndrome • B12/Folic Deficiencies • Hypothyroidism

15. What about the platelet count in Pregnancy? • Normal physiology – platelet counts are lower in pregnancy!! • Cause for this drop in pregnancy is unknown – proposed theories include • dilution • decreased platelet production • increased platelet turnover during pregnancy

17. Thrombocytopaenia in Pregnancy • How common? • 6-10% of pregnant ladies • Pregnancy – specific causes of thrombocytopaenia • Gestational Thrombocytopaenia • Preeclampsia/ Eclampsia • HELLP Syndrome • Acute Fatty Liver

18. Thrombocytopaenia in Pregnancy • Other Non- Pregnancy specific causes

20. Gestational Thrombocytopaenia • MOST COMMON CAUSE OF LOW PLATELETS IN PREGNANCY • 70% of cases of low platelets • late 2nd or 3rd trimester • Usually mild • Unusual for platelets to be < 70 x109/L

21. Gestational Thrombocytopaenia Diagnosis of exclusion Might not be possible to differentiate with ITP Might make epidural anaesthesia troublesome – might need platelet transfusion Does not respond to ITP treatment(ie steroids/ IVIG) Resolved post delivery 1-2 months

22. ITP in Pregnancy • Rare – about 5% to 10% of causes of low platelets in pregnancy • compared to Gestational Thrombocytopaenia(70+%) and hypertensive disorders in pregnancies(20+%) • 1 in 1,000 to 1 in 10,000 pregnancies

23. Estimated Various Forms of ITP

24. ITP in Pregnancy Goal of treatment – Prevent Bleeding Treatment is generally not required if Platelets are > 20-30x109/L Might need to keep it higher if planned LCSC or for epidural anaesthesia

25. www.moh.gov.my/attachments/3911

26. ITP in Pregnancy • Diagnosis – • Diagnosis of exclusion • BMA usually unnecessary unless suspecting MDS/Leukaemia/ Lymphoma

27. ITP in Pregnancy • Management before term (36weeks) • Asymptomatic with Plt > 20 x 109/L • No treatment • To expect platelets to drop after 36 weeks • Symptomatic or Plt < 20 x 109/L • Corticosteroids • IVIG

28. ITP in Pregnancy • Management after 36 weeks • Plt > 30 x 109/L (Malaysian CPG) – safe for vaginal delivery • Mode of delivery is always based on Obstetrics indications (Malaysian CPG) and not platelet counts!!!

29. ITP in Pregnancy • Management after 36 weeks • If Caesarian section is required for obstetric indications • iv corticosteroids if platelet count 30-50 x 109/L • IVIG and iv corticosteroids if platelet count <30 x 109/L • IVIG and iv corticosteroids plus platelet transfusion if platelet count <10 x 109/L

30. ITP in Pregnancy • Management during labour • Platelet count above 50 x 109/L is safe for caesarian section under general anaesthesia • Epidural anaesthesia is best avoided • If platelet counts < 50 x 109/L and emergency LSCS is required: • Give – IVIG, IV Methylprednisolone immediately • Give platelet transfusion just prior to surgery

31. ITP in Pregnancy ‘Safe’ Platelet Thresholds for delivery • vaginal delivery: > 30 x 109/L • caesarean section: > 50 x 109/L • epidural anaesthesia: > 80 x 109/L

32. ITP in Pregnancy – What I would do…or what I have learned from my sifus • Determining if there are any unusual bleeding tendencies ( - deciding if the patient is a so called bleeder or non-bleeder) – careful history taking • If non- bleeder and no obstetric risks factors, I tend to monitor rather than give treatment

33. ITP in Pregnancy – What I would do…or what I have learned from my sifus • Determining if the patient is a responder to treatment or not (?full recovery, partial recovery of platelet counts) • Careful history and notes review • steroid responsiveness • IVIG responsiveness – bear in mind repeated IVIG might cause refractoriness to IVIG

34. ITP in Pregnancy – What I would do…or what I have learned from my sifus • If unsure of treat, I would give a trial of treatment especially for moderate to severe thrombocytopaenia, this is only if there is time to play with… • Early in pregnancy – trial of steroids • Still time but Limited – trial of IVIG

35. ITP in Pregnancy – What I would do…or what I have learned from my sifus • If treatment responsive and indeed platelet drops nearing term • I would start steroids and anticipate an increase from about 1-2 weeks • I would start IVIG and anticipate an increase in from 3-5 days but likely only lasts about 1-2 weeks

36. ITP in Pregnancy • Neonatal care • Neonatal thrombocytopaenia in pregnant ladies with ITP is unpredictable • NOT correlated to platelet count, maternal antibodies, or other factors • Only Consistently known risks factor is history of a sibling with neonatal thrombocytopaenia

37. ITP in Pregnancy • Neonatal care • Paediatrician/ Neonatologist should be alerted • Platelet count nadir might be 2-5 days post natal

38. ITP in Pregnancy • A note about other forms of treatment • No evidence about safety, efficacy and thus not recommended

39. References Platelet Analysis Overview, Sysmex Xtra Online, Volume No 2, December 2007 ASH Education Book 2010 - Immune Thrombocytopenia by Adam Cuker and Douglas B. Cines ASH Education Book 2010 - Thrombocytopenia in Pregnancy by Keith R. McCrae CLINICAL PRACTICE GUIDELINES – MANAGEMENT OF IMMUNE THROMBOCYTOPENIC PURPURA, August 2006, MOH/P/PAK/115.06 (GU)

40. Thank you