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Obstetrical Management of Women with HELLP

Obstetrical Management of Women with HELLP. Siri L. Kjos, MD Harbor-UCLA Medical Center Good Samaritan Hospital 2/16/2010. Learning Objectives. State definitions of hypertensive disorders of pregnancy State the risk factors for preeclampsia

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Obstetrical Management of Women with HELLP

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  1. Obstetrical Management of Women with HELLP Siri L. Kjos, MD Harbor-UCLA Medical Center Good Samaritan Hospital 2/16/2010

  2. Learning Objectives • State definitions of hypertensive disorders of pregnancy • State the risk factors for preeclampsia • Define pathologic changes which occur in preeclampsia • Define HELLP and severe preeclampsia • Give a management strategy for preeclampsia/HELLP based on severity and gestational age • Give the evidence for magnesium sulfate preventing seizures

  3. Background: Classification of Hypertensive Disorders in Pregnancy Chronic hypertension Preeclampsia-eclampsia Preeclampsia superimposed on chronic HTN Gestational hypertension Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy AJOG 2000;183:s1-22

  4. Classification: Chronic Hypertension • Hypertension: SBP ≥ 140 mmHg or DBP ≥ 90 mmHg • Chronic hypertension • HTN before pregnancy • HTN diagnosed before the 20th week of gestation • HTN diagnosed during pregnancy that does not resolve post partum Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy AJOG 2000;183:s1-22

  5. Classification: Preeclampsia • Hypertension: • SBP ≥ 140 mmHg or DBP ≥ 90 mmHg • which occurs after 20 weeks in a woman who was previously normotensive • Proteinuria • Urinary excretion > 300 mg protein/24H Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy AJOG 2000;183:s1-22

  6. Classification: Preeclampsia and Eclampsia Important Notes: “Edema occurs in too many women with normal pregnancies to be a discriminator and has been abandoned as a marker” Even without proteinuria, preeclampsia is highly suspected when HTN is accompanied by: headache, blurred vision, abdominal pain, low platelet counts and/or abnormal liver enzyme values Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy AJOG 2000;183:s1-22

  7. Key Changes in Classification 2000 Preeclampsia • Diagnostic criteria no longer used • SBP rise ≥ 30 mmHg • DBP rise ≥ 15 mmHg • Edema - not sufficiently specific • A BP rise 30/15 above baseline warrants “close supervision” Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy AJOG 2000;183:1-22

  8. Diagnostic Criteria of Severe Preeclampsia One or more of the following: • SBP > 160 mmHg or DBP > 110 mmHg on 2 occasions at least 6 hours apart while patient is on bedrest • Proteinuria > 5g/24H or random urine +3 or greater on 2 specimens at least 4 H apart • Oligouria < 500 ml/24H • Cerebral or visual disturbances • Pulmonary edema or cyanosis • Epigastric or RUQ patin • Impaired liver function • Thrombocytopenia • Fetal growth restriction

  9. Classification: “Superimposed Preeclampsia” Preeclampsia superimposed on Chronic Hypertension • Onset of proteinuria (≥ 0.3 gm/24 hr) beyond 20 weeks in previously non-proteinuric patient with CHTN • In a patient with CHTN and established proteinuria: • Sudden increase in proteinuria • Sudden rise in BP that was previously controlled • Thrombocytopenia (platelet count <100,000/mm3) • Rise in serum transaminases Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy AJOG 2000;183:1-22

  10. Classification: Gestational Hypertension* • HTN diagnosed beyond 20 weeks without proteinuria • If proteinuria develops, the diagnosis becomes preeclampsia-eclampsia • If proteinuria does not develop, definitive diagnosis must wait until 12 weeks postpartum • *Note that the diagnosis of “gestational hypertension” is used during pregnancy only until a more specific diagnosis can be assigned post partum Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy AJOG 2000;183:1-22

  11. Hypertension diagnosed beyond 20 weeks Preeclampsia Gestational Hypertension HTN persists beyond 12 weeks postpartum HTN resolves by 12 weeks postpartum “Transient hypertension of pregnancy” Chronic hypertension Hypertension in Pregnancy Gestational Hypertension Proteinuria No Proteinuria Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy AJOG 2000;183:1-22

  12. Chronic HypertensionTreatment algorithm SBP > 140 or DBP > 90 on multiple occasions  End organ involvement?   Yes No   SBP ≥ 150 OR DPB ≥ 100 SBP < 150 AND DPB < 100   Pharmacologic therapy Non-pharmacologic therapy

  13. Preeclampsia • Incidence 5-7% in US • Unique to human pregnancy • Genetic component? • Preeclampsia in the patient’s mother? • 3 categories of Risk factors • Hypertensive disorders • Abnormal placental size or function • Young primigravida

  14. Preeclampsia: Risk Factors • Hypertensive disorders • Chronic hypertension • Renal disease • Diabetes with vasculopathy • Collagen vascular disease • Thyroid disease • Age > 40

  15. Preeclampsia: Risk Factors Abnormal placental size or function • Diabetes with large placenta • Multiple gestation • Hydatidiform mole • Fetal hydrops with placentomegaly • APL syndrome with small placenta

  16. Endothelial cell dysfunction Endothelial cell damage Decreased production of PGI2 Exposure of collagen – tissue factor Platelet aggregation activation “Leaky” capillaries Reversed PGI2:TXA2 ratio Activation of clotting cascade Proteinuria Decreased COP Vasoconstriction -  SVR Hypertension Thrombocytopenia, DIC Edema

  17. Endothelial Damage Endothelial damage Serum from Fibronectin preeclamptic PDGF B patient VCAM-1 Endothelin EDRF (Nitric oxide) Decreased PGI2 Cultured endothelial cells Serum from same patient 6 wks postpartum does not have this effect Serum from pregnant non-preeclamptic at the same gestation age does not have this effect

  18. Any Evidence? Placental hypoxia?? Placental release of factor(s) that alter endothelial cell function

  19. Placental Hypoxia Cultured trophoblast Thromboxane Interleukin 1 Tumor necrosis factor Hypoxic Placenta Maternal Endothelium

  20. Hypertensive disorders • Chronic hypertension • Renal disease • Diabetes • Collagen vascular • Thyroid disease • Abnormal placenta • Diabetes • Multiple gestation • Hydatidiform mole • Placentomegaly • APL syndrome Young Primigravida???? No medical complications, no reason to have poor placental perfusion. How can we explain this risk category? Poor placental perfusion Placental hypoxia Placental release of factor(s) that alter endothelial cell function

  21. Placenta in Preeclampsia Abnormal "second wave" of endovascular trophoblast migration Cytotrophoblast invasion: histopathology 1st trimester Decidual segments of spiral arteries Degeneration of muscular layer Low-resistance, distended, funnel-shaped Early 2nd trimester Myometrial segments of spiral arteries Retain musculoelastic architecture, high resistance Endothelial injury, fibrin deposition, atherotic changes Responsive to endogenous vasoconstrictors Decreased uteroplacental blood flow - placental hypoxia

  22. TROPHOBLAST INVASION OF SPIRAL ARTERIES NORMAL PREGNANCY PREECLAMPTIC PREGNANCY

  23. Normally, invading trophoblasts convert surface antigens to resemble endothelial cells Retention of trophoblast antigens permits recognition by maternal decidual NK cells and limitation of depth of invasion What causes failure of normal trophoblast invasion? Trophoblasts of preeclamptics fail to make this conversion

  24. Management of Preeclampsia • Delivery is the only cure. • The decision for immediate delivery versus expectant management is based upon: • Disease Severity • Fetal Maturity • Maternal and fetal condition • Cervical status

  25. Induction of labor vs. expectant monitoring for Gestational HTN or Mild Preeclampsia after 36 weeks of gestation (HYPITAT): multicenter, RCT Study: RCT in Netherlands, 38 hospitals (2005-08), Inclusion: Singleton gestation 36/0-41/0 wks, n=756 with GHTN or Mild Preeclampsia randomized to induction (n= 377) vs. expectant management (n=397) 1 ⁰ Outcome: Composite maternal outcome (mortality, eclampsia, HELLP, Pulm edema, thromboembolicdz, abruption, progression to severe dz, PP hemorrhage >1000 cc) Koopmans CM, et. al.Induction of labor vs. expectant monitoring for Gestational HTN or Mild Preeclampsia after 36 weeks of gestation (HYPITAT): multicenter, RCT . Lancet 2009, 374:979-989.

  26. Induction of labor vs. expectant monitoring for Gestational HTN or Mild Preeclampsia after 36 weeks of gestation (HYPITAT) Koopmans CM, et. al.Induction of labor vs. expectant monitoring for Gestational HTN or Mild Preeclampsia after 36 weeks of gestation (HYPITAT): multicenter, RCT . Lancet 2009, 374:979-989.

  27. Induction of labor vs. expectant monitoring for Gestational HTN or Mild Preeclampsia after 36 weeks of gestation (HYPITAT) Koopmans CM, et. al.Induction of labor vs. expectant monitoring for Gestational HTN or Mild Preeclampsia after 36 weeks of gestation (HYPITAT): multicenter, RCT . Lancet 2009, 374:979-989.

  28. HYPITAT: Risk of Composite Poor Maternal Outcome Conclusion Induction of labor is associated with improved maternal outcome and should be advised for women with mild hypertensive disease (gestational hypertension and mild preeclampsia) beyond 37 weeks Women with unfavorable cervix (not dilated, effacement <25%,posterior cx position) had greatest benefit from induction: Paradox: If had an unfavorable cx and allocated to expectant management, had longer time to delivery and greater risk of deteriorating maternal condition! Koopmans CM, et. al.Induction of labor vs. expectant monitoring for Gestational HTN or Mild Preeclampsia after 36 weeks of gestation (HYPITAT): multicenter, RCT . Lancet 2009, 374:979-989.

  29. Mild Preeclampsia Hospitalize > 40 weeks 37-40 weeks < 37 weeks Unfavorable cervix Favorable cervix Cervical "ripening" agents MgSO4 + Expectant management Bedrest, regular diet Delivery Serial maternal and fetal evaluation

  30. Severe Preeclampsia Beyond 34 weeks or Evidence of pulmonary maturity or Fetal or maternal compromise Magnesium Sulfate Blood pressure control DELIVERY

  31. Deliver Expectant management Regardless of fetal maturity Corticosteroids Antihypertensives Frequent testing Deliver at 34-35 weeks Severe Preeclampsia < 34 weeks gestation CONTROVERSIAL Sibai, Preeclampsia Diagnosis and Management

  32. > 34 wks MgSO4+Deliver MgSO4 + Consider amniocentesis 32-34 wks Steroids if immature + Deliver after 24-48 hrs MgSO4+antihypertensives as needed Counsel regarding risks/benefits of expectant 24-32 wks* management Steroids + Close maternal/fetal surveillance Deliver for fetal or maternal indications <24 wks* Consider termination (PGE2, Cytotec, PGF2a) Severe Preeclampsia Gestational age Management - Hospitalization *Consultation with perinatology, neonatology, referral to tertiary center appropriate

  33. Treatment of Acute Severe Hypertension Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy AJOG 2000;183:1-22

  34. Intrapartum Management Eclampsia: 1:300-1,000 Seizures are usually self-limited (1-2 minutes) Prevent aspiration of gastric contents Diazepam or Ativan only if sustained Prolonged deceleration will recover after seizure If possible, allow time for full fetal recovery Cesarean only if vaginal birth not possible within a reasonable time frame

  35. HELLP Syndrome Complicates ~10% of cases of severe preeclampsia Complicates 30 to 50% of cases of eclampsia Blood pressure, proteinuria, uric acid may be normal Hemolysis Elevated liver enzymes Low Platelets

  36. HELLP Syndrome • 1-2 per 1000 pregnancies • 10-20% women with severe preeclampsia develop HELLP • 15-20% of patients with HELLP don't have HTN or proteinuria • Majority of cases diagnosed between 28-36 weeks gestation

  37. HELLP: Morbidity and Mortality • Isler et al (1999) • 54 materal deaths secondary to HELLP syndrome • Results • Cause of Death • Cerebral hemorrhage (45%) • Cardiopulmonary arrest (40%) • DIC (39%) • ARDS, renal failure, sepsis, hepatic hemorrhage • Mortality %: Platelet count • 60% : PLT < 50,000 • 35% : 50,000 < PLT < 100,000 • 4.4 %: PLT > 100,000

  38. HELLP Syndrome:Sibai criteria or “Tennessee Classification” 4 • Hemolysis: LDH  600 • Elevated liver enzymes: AST  70 U/L • Low platelets  100,000 • Occurs in approximately 20% of pt’s with severe preeclampsia • Associated with placental abruption, renal failure, subcapsular hepatic hematoma, preterm delivery, and fetal or maternal death 4. Sibai BM. The HELLP syndrome (hemolysis, elevated liver enzymes and low platelets): much ado about nothing? Am J Obstet Gynecol 1990; 162:311-16.

  39. Spectrum of disease: Severe preeclampsia and HELLP • Sibai proposed three entities: • Severe preeclampsia (no lab abnormalities) • Partial HELLP Syndrome (only 1-2 criteria met) • HELLP Syndrome (all 3 criteria met) • 1. Hemolysis: LDH > 600 IU/L • 2. Elevated liver enzymes: AST > 70 IU/L • 3. Low platelets  100,000 K

  40. HELLP Syndrome: Mississippi Classification 5 HELLP ClassPlateletsAST or ALTLDH I  50,000  70 IU/L  600 IU/L II 50-100,000  70 IU/L  600 IU/L III 100-150,000  40 IU/L  600 IU/L Most predictive symptom is epigastric pain or RUQ discomfort found in: Class I- 50% Class II- 33% Class III- 16% 5. Martin JN et al. The natural history of HELLP syndrome: patterns of disease progression and regression. Am J Obstet Gynecol. 1990; 76:737-41

  41. When should a woman with Partial or Class I HELLP be delivered when her fetus is premature? • Is the patient stable for steroid window? • Can pt be managed expectantly  48hrs?

  42. Severe Preeclampsia vs. HELLP Study: Case-control study of severe preeclampsia vs. HELLP syndrome < 34 wks GA Results: Found no difference in neonatal or maternal outcomes: Perinatal mortality 14.1% Conclusion: Temporizing measures, similar to those in severe preeclampsia, could be undertaken in women with HELLP, and could improve fetal, neonatal, and maternal outcome Visser et al. Temporizing management of severe preeclampsia with and without HELLP syndrome. Br J obstet Gynecol. 1995; 102:111-117

  43. HELLP: Maternal Complications * p<0.001; + DIC defined as plt<100k, fibrinogen <300mg/dl, and +FDP or elevated INR Audibert FA, Sibai BM, et al. Clinical utility of strict diagnostic criteria for the HELLP syndrome. Am J Obstet Gynecol 1996; 175: 460-64.

  44. HELLP: Maternal Complications * p<0.001; + DIC defined as plt<100k, fibrinogen <300mg/dl, and +FDP or elevated INR Audibert FA, Sibai BM, et al. Clinical utility of strict diagnostic criteria for the HELLP syndrome. Am J Obstet Gynecol 1996; 175: 460-64.

  45. Maternal Morbidity: based on HELLP Class • * Test for linear trend based on classification system; + includes Renal, CNS, and Hepatic/GI • Retrospective review of 777 pregnancies, at single institution Martin JN et al. The spectrum of severe preeclampsia: comparative analysis by HELLP syndrome classification. Am J Obstet Gynecol. 1999; 180:1373-84.

  46. Maternal indications for delivery  48hrs in women with severe preeclampsia • Uncontrolled severe HTN ( 160 systolic or  110 diastolic) despite maxium doses of at least two HTN meds • Eclampsia or Pulmonary edema • Placental Abruption • Oliguria, unresponsive to fluid challenge • Persistent severe headache or visual disturbance • Peristentepigastric pain or RUQ tenderness • HELLP syndrome or platelet <100K • Deterioration of renal function (Cr >1.4 mg/dl) Haddad B, Sibai BM. Expectant management of severe preeclampsia: proper candidates and pregnancy outcome. Clinical Obstet and Gynecol. 2005. Vol.48. No.2 430-440.

  47. Severe preeclampsia: Expectant Management >48hrs • Sibai (1994): Randomized trial, delivery @48hrs vs. expectant management @ 28-32 wks • Average latency 15.4 days, • Higher birthweight (1622 vs. 1233g) • Lower NICU admissions (76 vs. 100%), no perinatal death • Haddad (2004): Prospective cohort of expectant management • Average prolongation @24-29 wks GA: 6 days • 5.4% perinatal deaths (12/222 patients) • No maternal death or eclampsia Sibai BM et al. Aggressive versus expectant management of sever preeclampsia at 28-32 weeks gestation: a randomized control trial. Am J Obstet Gynecol. 1994; 171:818-822. Haddad B, et al. Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24-33 weeks gestation. Am J Obstet Gynecol. 2004. 190:1590-97.

  48. Summary: Expectant management with Severe Preeclampsia • Administer 48hr steroids and reassess status • Any fetal indication for delivery? (IUGR, antenatal testing) • Can meet maternal criteria for expectant management if: • - epigastric pain resolves • - headache and blurry vision resolves • - platelets stay >100K • - BP can be controlled <160/110 mmHg • - Creatinine stays <1.4 mg/dl

  49. Expectant Management Plan with Preterm Severe preeclampsia • Bedrest, Daily weight, strict I’s/O’s • Continuous FHM, Tocometry • Aggressive BP management • Magnesium Sulfate • Antenatal corticosteroids • Frequent HELLP labs, renal function • NICU and anesthesia consult • Counseling regarding risks and benefits of delaying delivery • Document plan and discussions

  50. HELLP: Medical Management Study Design: RCT Dexamethasone 10 mg IV q 12H vs. control • Outcome: Comparead to control, dexamethasone group had more rapid improvement in: • Urinary output • Mean arterial pressue • Platelet count • LDH and SGOT levels Magann AJOG 1994;171:1154-8, Magann Aust NZ J Obstet Gynaecol 1993:33;127

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