Thrombocytopenia & Seizures.pptx
- 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