Thrombocytopenia with seizures in pregnancy can indicate serious conditions like preeclampsia/eclampsia, HELLP syndrome, TTP, or HUS. Preeclampsia is the most common cause, resulting from endothelial cell damage leading to platelet activation and coagulation. Management involves blood pressure control, seizure prevention with magnesium sulfate, and timely delivery. Differentiating these microangiopathies can be difficult but is important for targeting appropriate treatment like plasma exchange for TTP. A multidisciplinary approach and delivery optimization are crucial for improving maternal and neonatal outcomes.

1. Thrombocytopenia & Seizures
in
Pregnancy
Dr.Madura Jayawardane(MBBS,MD,MRCOG)
Senior Lecturer
University of Sri Jayawardenapura

2. Platelets
Non nucleated cells
Originates from megakaryocytes
Half life of 8-10 days in peripheral blood
Critical for initiation of haemostasis when activated
Normally levels vary between 150-400×109/L

3. Physiological changes to platelets in pregnancy
• Number of circulating platelets declines (as POG advances) to lower
normal level-150×109 /L.
• Platelet aggregation ability increases
• Platelet lifespan declines
• Platelet volume minimally increase

4. Reasons for physiological changes to platelets
• Increased consumption of platelets in the utero-placental circulation
• Hemodilution

5. Thrombocytopenia in pregnancy
• A platelet count of less than 150×10 9/L is known as
thrombocytopenia
• A platelet count below the normal range is found in 8–10% of
pregnancies
• Most cases are mild and have no significance for mother or foetus
• Occasionally complex pathologies with severe morbidity and
mortality can be seen

6. Causes for thrombocytopenia in pregnancy

7. Is every thrombocytopenia bad?
• 75% of cases are due to a benign process of gestational
thrombocytopenia
• 15–20% related to hypertensive disorders in pregnancy
• 3-4% related to immunological disorders
• 1-2% of all due to infections, malignancies or rare platelet disorders

8. Causes for thrombocytopenia with seizures
• Unless no ICH or infective origin causes very few pregnancy related
events can cause this presentation.
• Pre-eclampsia/Eclampsia
• HELLP
• TTP
• HUS
• AFLP & Encephalopathy

9. Eclampsia/Pre-eclampsia
• Eclampsia - convulsive condition associated with pre-eclampsia.
• Pre-eclampsia- de novo hypertension(140/90mmHg) after POG 20
weeks with 1 or more following conditions
Proteinuria-UPCR>30 or ACR>8 or Dipstick +2 (>1g/L)
Utero-placenta insufficiency
Maternal organ dysfunction (blood-low platelets, CNS-fits, liver or
renal problems)

10. Pathogenesis
• Women with preeclampsia have lower platelet counts than normal
• Approximately 15% within the thrombocytopenic range
• This is related to increased endothelial cell activation leading to the
activation of platelets and the coagulation cascade
• Seizures occurs as a result of cerebral oedema and vasospasm

11. • Severe thrombocytopenia occurs among 5% of women with pre-
eclampsia
• Unless very severe illness, condition recover following delivery
• But recurrence for next pregnancy is high as 2-5 times that is
approximately 16%

14. Why condition resolves after delivery?
• The utero-placental ischemia causes the release of various vasoactive
molecules (Endoglin, Soluble FMS like tyrosine kinases)
• After placenta is expulsed, abrupt decline of molecules cease
pathology and platelets recover over about next 7-10 days.

15. Management of pre-eclampsia/eclampsia
• 1-Blood pressure control-Oral/IV anti-hypertensives (current first line
is Labetolol)
• 2-Seizure prevention –Drug of choice IV Magnesium sulphate
• 3-Consider delivery depend on degree of severity and foetal condition
in liaise with neonatology team
• 4-Steriods for foetal lung maturity

16. • 5-Multi disciplinary team involvement for maternal condition
optimization
Eg-those who have DIC need to be optimized with haematologists and
transfusion specialists input in a ICU. Those patients require blood and
blood products.

17. HELLP Syndrome
• This is a combination of haemolysis, elevated liver enzyme levels and
low platelet counts
• HELLP syndrome occurs in approximately 0.2 to 0.6 percent of all
pregnancies
• Complicate severe pre-eclampsia in about 10% of cases
• It occurs most frequently in the third trimester
• Can occur without hypertension or proteinuria (which makes delay in
diagnosis)
• The presenting symptoms can be very vague, with nausea, malaise
and epigastric or right upper quadrant pain

18. Pathophysiology

19. • Pathogenesis of HELLP syndrome is not well understood
• This multisystem disease is attributed to abnormal vascular tone,
vasospasm and coagulation defects
• Syndrome seems to be the final manifestation of an insult that leads to
micro vascular endothelial damage and intravascular platelet activation
• All patients with HELLP syndrome may have an underlying coagulopathy
that is usually undetectable. Most patients show no abnormalities on
coagulation studies.

20. • The haemolysis in HELLP syndrome is a microangiopathic haemolytic
anaemia
• Red blood cells become fragmented as they pass through small blood
vessels with endothelial damage and fibrin deposits
• The elevated liver enzyme levels is due to obstruction of hepatic
blood flow by fibrin deposits in the sinusoids
• The thrombocytopenia has been attributed to increased consumption
and/or destruction of platelets.

21. • Disseminated intravascular coagulation may be present in
approximately 20% of cases
• Abruption occurs in approximately 16%
• The central nervous and renal systems are usually unaffected by this
condition, in contrast to TTP

22. • Depend on liver enzymes and platelet levels, incomplete forms of
HELLP syndrome has been described.

23. Management
• Delivery is the treatment for the mother
• Steroids should be given (only to help mature the baby’s lungs)-but NICE
guideline do not support high dose steroids to mother in order to improve
HELLP syndrome.
• The platelet count should be maintained at >50 and MDT approach is often
improve care
• condition usually improves quite quickly after delivery, although it may
worsen during the first 24–48 hours postpartum

24. Thrombotic thrombocytopenic purpura-TTP
• A microangiopathic condition
• Rare (1/25000 pregnancies) and life-threatening
• Pentad of symptoms and signs
• The time of onset in pregnancy is variable
• Mostly occurs in 2nd trimester
• Highest mortality is when condition starts de novo in pregnancy and
co-exist with pre-eclampsia

25. Fever

26. Pathogenesis

27. • Due to a severe deficiency of von Willebrand’s factor-cleaving protein
(ADAMTS 13)
• leads to persistence of ultra-large multimers of von Willebrand’s
factor that unfold and react with platelet receptors
• Generates microthrombi in many organs,particularly in the kidneys,
brain and heart, and causing microangiopathic hemolytic anemia and
thrombocytopenia
• Condition is difficult to diagnose

28. • Most commonly an acquired deficiency caused by an autoantibody
• rarely, a primary congenital deficiency caused by a genetic defect
• The two types can be distinguished by measurement of ADAMTS 13
antigen activity and inhibitor
• Inhibitor is absent in the congenital form.

29. Management
• Plasmaparesis-to remove antibodies is the cornerstone of
management
• 1–1.5 l fresh frozen plasma containing the absent enzyme is infused
daily until the platelet count & LDH normalize.
• Number of treatment cycle is variable
• Immune suppression with high dose steroids or use of Rituximab
against CD20 cells are known alternative options when condition
resists.

30. • Recurrence for subsequent pregnancy is high as 1 in 4 (25%)
• When the condition is congenital, Plasmaparesis is not effective as
there is no specific antibody forms to remove
• These patients are best treated with plasma infusion only
• Platelet transfusion is contraindicated as it aggravates CNS
symptoms

31. • The risk of bleeding is low in this condition
• Relapses can be predicted by previous clinical manifestation pattern
and low level of ADAMTS 13 during remission

32. HUS-Haemolytic uremic syndrome
• Similar to TTP-microangiopathic condition
• Triad of symptoms and signs
• Renal failure is marked
Non-immune,
MAHA

33. • Typical HUS-associated to shiga toxin and seen in children
• Atypical HUS-seen in adults and related to complement dysregulation
• Pregnancy is linked to Atypical-HUS
• High morbidity and mortality

34. Pathogenesis
• Acquired or constitutional complement alternative pathway
dysregulation
• leading to complement-induced endothelial cell damage in atypical
HUS
• Various patterns of endothelial cell lesions in the heterogeneous
group of secondary HUS associated with autoimmune diseases, drugs,
infections, and pregnancy.

36. AKI is frequently encountered in most
types of pregnancy-associated TMA,
except TTP

37. Laboratory findings common to thrombotic
micro-angiopathies
• Platelet count <100
• Hemoglobin level <10
• LDH level >1.5 upper limit of normal
• Undetectable serum haptoglobin
• Coomb test negative
• Schistocytes on blood smear (MAHA favoring smear)

38. HUS-Management
• Plasma exchange or infusion are the traditional methods
• But effective in 50% cases
• The humanized monoclonal anti-C5 antibody (Eculizumab) has
radically improved the prognosis and safe in pregnancy
• MDT approach and optimization to delivery of foetus is important

39. Microangiopathies and neonatal issues
• prognosis for the baby in all the Microangiopathies described is poor
because of extensive placental ischemia

40. How to differentiate these pathologies?

41. References
• 1) D L W Dasanayake, Y Costa, A Weerawardana.Management of thrombocytopenia in
pregnancy.Sri Lanka Journal of Obstetrics and Gynaecology 2021; 43: 259-
268(DOI:http://doi.org/10.4038/sljog.v43i3.8020)
• 2) Mayers B.Thrombocytopenia in pregnancy.TOG;2009;11:177–183.
• 3) Paddon MO. HELLP Syndrome: Recognition and Perinatal Management. Am Fam Physician.
1999;60(3):829-836
• 4) Management of thrombotic microangiopathy in pregnancy and postpartum: report from an
international working group. https://doi.org/10.1182/blood.2020005221
• 5) Gernsheimer T, James AH, Stasi R. How I treat thrombocytopenia in pregnancy. Blood. 2013 Jan
03;121(1):38-47
• 6) George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med. 2014 Nov
06;371(19):1847-8

42. In summery
• Not all thrombocytopenia's are bad or fatal
• When it coexist with seizures-need to rule out pregnancy related
unique conditions
• Chronic epilepsy with low platelet causing medical conditions to be
considered as well
• Microangiopathies make diagnosis more complicated
• MDT approach and optimization for delivery is often safe for mother
and baby