Preeclampsia

Question 1

Different types of hypertension in pregnancy

Answer 1

• Chronic/preexisting hypertension - hypertension that precedes pregnancy or presents before 20th week gestation
• Gestational hypertension - hypertension without proteinuria or other signs/symptoms of preeclampsia-related end-prgan dysfunction that develops after 20 weeks of gestation
• Preeclampsia - onset of hypertension and either proteinuria or end-organ dysfunction after 20 weeks gestation
• Preeclampsia superimposed upon chronic/preexisting hypertension - new onset proteinuria, significant end-organ dysfunction, or both after 20 weeks gestation in women with preexiting hypertension

Question 2

Pathogenesis Preeclampsia

Answer 2

• Abnormal development of the placenta plays a criterial role in the development of preeclampsia. In normal placental development the cytotrophoblast of the developing placenta migrate through the decidua and myometrium, invading the endothelium and tunica media of spiral arteries (terminal branches of uterine artery that supply the placental). With the invasion, the small arterioles turn into large capacitance vessels with low resistance, encouraging a lot of blood flow to the palcenta. This process is generally completed by 18-20 weeks.
• In preeclampsia the cytotrophoblast do not penetrate the myometria. Thus, the sprial arteries stay narrow, and the placenta is underperfused. This also results in endothelial dysfunction where vasconstrictive substances (endothelin and thromboxane A₂) dominates over vasodilators.

Question 3

Screening for Preeclampsia

Answer 3

• Universal routine blood pressure measurement in pregnancy - all women should be screened and blood pressure taken at each visit. Eventhough preeclampsia can’t be diagnosed before 20 weeks, it is good to get a baseline.
• Identifying women at high risk (should be given aspirin to reduce risk)
  
  • High risk: previous preeclampsia, multifetal gestation, chronic hypetension, DM 1 or 2, renal diseasem autoimmune disease (antiphopholipid syndrome, systemic lupus erythematosus), CKD
  • Moderate risk: Nulliparity, obesity, family history of preeclampsia, age ≥ 35 years, Aferican American, low SES
• Women should get urinalysis for proteinuria at first prenatal visit to establish baseline and repeat once in normotensive patients. In hypertensive patients, presence of proteinuria changes the diagnossi to preeclampsia

Question 4

Diagnostic Criteria of Preeclampsia

Answer 4

• Diagnosis should be made when previously normotensive women has new onset hypertension (systolic ≥ 140 or diastolic ≥ 90) on two separate occasions at least four hours apart and either proteinuria or signs or symptoms of significant end organ dysfunction after 20 weeks gestation (persistant and/or severe headaches, visual abnormalities, upper abdominal or epigastric pain, altered mental status, dyspnea, retrosternal chest pain).

Question 5

Potential Lab Findings in Preeclampsia

Answer 5

• Proteinuria ≥ 0.3g protein in 24hr urine specimen
• Elevated creatinine - during pregnacy there is an increase in GFR resulting in decrease serum creatinine concentration. In preeclampsia GFR remains at this level or slightly elevated creatinine indicated severe preeclampsia (Preeclampsia is msot common cause of AKI in pregnancy).
• Decreased platelet count - platelet count is normal unless patient has severe preeclampsia (<100, 000 platelets/micro/L)
• Hemolysis - schistocytes suggest microangiopathic hemolysis, which is a finding of severe disease
• Coagulation studies - PTT, INR, and fibrinogen concentration are not affected by preeclampsia unless there are other complications (abruptio placenta, severe bleeding, or severe liver dysfunction).
• Liver chemistries - liver function tests are normal, expect at severe end of disease spectrum, characterized by elevated transaminase levels
• Hyperuricemia - due to reduction in GFR
• Follow up - if diagnosed with preeclampsia, weekly tests for platelet count, serum creatinine, and liver enzymes should be done to test for disease progression

Question 6

Diagnostic Criteria of Preeclampsia with Severe Features

Answer 6

• Diagnosis is made after 20th weeks gestation in previously normotensive women who develop
  
  • Systolic ≥ 160 or diastolic ≥ 110 and proteinuria (with or without signs and symptoms of significant end-organ dysfunction).
  • Systolic ≥ 140 or diastolic ≥ 90 (with or without proteinuria) and one or more of the following signs and symptoms of significant end-organ dysfunction
    
    • New onset cerebral or visual disturbances (photopsia, severe headaches, altered mental status)
    • Severe, persistant RUQ or epigastric pain unresponsive to meds
    • < 100,000 platelets/microL
    • progessive renal insufficiency (serum creatinine >1.1mg/dL)
    • Pulmonary edema

Question 7

Potential Sonographic Findings in Preeclampsia

Answer 7

• Fetal ultrasound - may be associated with suboptimal fetal growth due to reduced uteroplacental perfusion
• Fetal growth restriction may be associated with olgiohydramnios due to redistribution of fetal circulation away from kidney and towards more vital organs
• Uterine and umbilical artery doppler - increase impedance to flow in uterine arteries due to uteroplacental maldevelopment is shown by elevated of pulsating index and uterine artery nothcing on uterine artery Doppler velocimetry.

Question 8

Management for preeclampsia

Answer 8

• The definitive treatment is delivery to prevent development of maternal or fetal complications from disease preogession. Timing of the delivery depends on severity, maternal and fetal and conidition, and gestational age.

1. Preeclampsia with severe disease
   
   • Delivery - preeclampsia with severe disease is an indication for delivery as it reduces the risks of serious maternal and fetal complications like cerebral hemorrhage, hepatic rupture, renal failure, pulmonary edema, seizure, abruptio placenta, or fetal growth restriction.
   • Conservative management - reasonable if pregnancy is preterm to reduce neonatal morbidity from preterm delivery. This should be considered for pregnancies ≥ 24 weeks and < 34 weeks. In these cases mother should be hospitalized and closely monitored.
2. Preeclampsia without severe disease
   
   • Delivery - recommended that women with preeclampsia deliver at ≥ 37 weeks
   • Conservative management - at preterm gestational ages the risk from progression needs to be balanced with risk of preterm. If the mother and fetus are stable without signs of serious end-organ dysfunction it is reasonable to just monitor. However, evidence of maternal end-organ dysfunction or indications of poor fetal well-being are indications for delivery.

Question 9

Antihypertensive therapy in preeclampsia

Answer 9

• Do not prescribe medications for mild hypertension in preeclampsia (BP <150/100). In these cases the benefits (reduction in risk of developing severe hypertension) does not outweight the risks (fetus exposure).
  
  • Lower BP does not affect course of preeclampsia becaus it is due to placenta vascular abnormalities
• If patient BP is >150/100 can give acute doses of various antihypertensive agents (labetalol, hydralazine, or Ca²⁺ channel blockers) to prevent stroke

Question 10

Antenatal corticosteriods in preeclampsia

Answer 10

• Should be given to all women with preeclampsia <34 weeks since they are at increased risk of progression to severe disease and preterm delivery. Course of steriods should be administered when it is believed delivery will be in the next 7 days (used to accelerate fetal lung maturation).

Question 11

Seizure prophylaxis in preeclampsia

Answer 11

• Eclampsia - occurance of new-onset, generalized, tonic-clonic (rigid-jerky) seizures or coma in a women with preeclampsia.
• Magnesium sulfate can be given to women intrapartum and postpartum to reduce risk of seizure

Question 12

HELLP Syndrome

Answer 12

• Hemolysis with mircoangiopathic blood smear, elevated liver enzymes, and low platelet count.
• Likely represents a severe from of preeclampsia

Question 13

Pathogenesis of HELLP syndrome

Answer 13

• Pathogenesis is unclear. Howevere, if it is a severe form of preeclampsia, it is likely due to abnormal placental development, but with greater hepatic inflammation and greater activation of the coagulation system.

Question 14

HELLP Presentation

Answer 14

• Proteinuria, hypertension, RUQ/epigastric pain, nausea/vomiting, headache, vision changes, jaundice
• Signs and symptoms typically develop between 29-36 weeks gestation, but second trimester or postpartum onset is also common

Question 15

Diagnosis of HELLP

Answer 15

• Hemolysis with microangiopathic blood smear
• Elevated liver enzymes (AST > 2 times upper limit of normal)
• Low platelet count ( ≤100, 000 cell/microL)
  
  • In severe cases may have DIC with prolongation of INR and PTT
• Total bilirubin >1.2mg/dL

Question 16

Management of HELLP

Answer 16

1. Stabilize mother, assess fetal condition, and determine whether prompt delivery is indicated
2. Antiyhypertensive drugs (labetalol) can be given to treat severe hypertension
3. Magesium sulfate - given to patients in labour to prevent convulsion and for fetal neuroprotection in pregnancies between 24-32 weeks
4. Delivery - Delivery is curative and only effective treatment. Delivery is indicated after maternal stabilization in any of the following:
   
   • Pregnancy ≥ 34 gestation or < 23 gestation
   • Fetal death
   • Nonreassuring tests or fetal status
   • Severe maternal disease: multiorgan dysfunction, DIC, liver infaraction or hemorrhage, pulminary edema, renal failure, or abruptio placenta.

• Pregnacy between ≥ 23 weeks and < 34 weeks - if both maternal and fetal status are reassuring, administer course of corticosteriods before delivery. Not advised to delay delivery beyond 48hrs due to potential for severe disease progression. Antihypertensive is given and mangesium sulfate for fetal neuroprotection.
  5. Indications for platelet transfusion - actively bleeding patients with thrombocytopenia should be transfused. If C-section is planned a transfusion can be done to have preoperative count > 40, 000 - 50, 000 cells/micrL
  6. Route of delivery - vaginal delivery is desirable if women is in labour or with ruptured membranes regardless of gestational age. C-section should be done if gestational age is less then 30-32 weeks and cervix is unfavourable for induction.

Question 17

Maternal Outcome in HELLP

Answer 17

• Following delivery mother generally improves with 48hrs. However, serious complications are not uncommon
  
  • DIC, abruptio plaentae, acute renal failure, pulmonary edema, liver hematoma, retinal detachment.

Question 18

Fetal Outcome if HELLP

Answer 18

• Very dependent on gestational age at delivery
• May have complications due to intrauterine growth restricition and affects from abruptio placenta

Question 19

Neuroprotective effects in utero exposure to magnesium sulfate

Answer 19

• Cerebral palsy is a leading cause of neurologic impairment - prematurity and low birth weight are leading cause
• In utero exposure to magnesium sulfate before preterm delivery decreases incidence and severity of cerebral palsy
• Mechanism for why this works is not well understood - may be due to stabilization of cerebral circulation, stabilization of neuronal membrane, protection against oxidative injury, and/or protective against inflammatory injury
• Canadiates - women at high risk of imminent (within 24hrs) preterm birth
• Contraindications - can’t be used in women with myasthenia gravis because it can cause a myasthenic crisis.

Question 20

DIC (Disseminated intravascular coagulation) in Pregnancy

Answer 20

• A disruption of balanced process of hemostasis. It is a secondary manifestation of an underlying primary cause of uncontrolled activation of coagulation.
• Characterized by systemic activation of blood coagulation, resulting in generation of fibrin and thrombi in the small vessels of the body, leading to organ dysfunction + excessive bleeding due to platelets and clotting factors being “used up”

Question 21

Pathophysiology of DIC

Answer 21

• Normal pregnacy is prothromobtic state with an increase in coagulation factors, impaired endogenous anticoagulation, redued firbrinolysis, and increased platelet activity. The reason for this is to prevent excessive hemorrhage during placental separation.
• Normally, there is a balance between fibrin formation and breakdown - DIC occurs when this balance fails
• In DIC, widespread activation of the clotting cascade causes intravascular fibrin deposition, fibrinolysis, depletion of coagulation factors and platelets, production of degradation products and D-dimers (interfere with platelet function and uterine contractility), and depletion of natural anticoagulants. Ultimately, this results in uncontrolled hemorrhage, microvascular thrombosis, and mutliorgan failure.

Question 22

Underlying causes of DIC in Pregnancy

Answer 22

• Abruptio placenta
• Post partum hemorrhage
• Preeclampsia/eclampsia/ HELLP
• Acute fatty liver of pregancy
• Amniotic fluid embolism
• Pregnancy related sepsis

Question 23

Presentation of DIC in pregnancy

Answer 23

• Patients may present with severe uterine bleeding and/or diffuse oozing of blood from skin or mucosa (uterine bleeding may be hidden if blood if retained behind placenta).
• Signs of shock - tachycardia, hypotension, weak peripheral pulses, altered mental status, cool extremities, narrow pulse oressure (<25mmHg)
• Organ dysfunction - acute kindey injury, hepatic dysfunction, acute lung injury, neurologic dysfunction.

Question 24

Laboratory Findings in DIC

Answer 24

• Thromobocytopenia - platelet count is usually mildly to moderately reduced in DIC
• Prolongation of PTT or INR - PTT and INR are prolonged in DIC. In normal pregnacy, PTT and InR may be slightly lower, this can result in delay of recognizition of coagulopathy
• Hypofibrinogenemia - fibrinogen levels fall in DIC. In normal pregnancy fibrogen levels are elevated. Reduction of fibrinogen from baseline is a late finding in DIC.
• Increased D-dimer - D-dimer is already elevated in pregnancy, but is even more so in DIC
• WBC - may be normal, increased, or decreased (due to infection) in DIC

Question 25

Criteria for DIC diagnosis

Answer 25

• Diagnosis is made when clinical setting is appropriate (ex. abruptio plaentae, aminotic fluid embolism, acute fatty liver, sepsis) + lab evidence of thrombocytopenia, coagulation factor consumption (increase INR, increase PTT, low fibrinogen), and fibrinolysis (increase D-dimer).

Question 26

Maternal Management of DIC in pregnancy

Answer 26

• Key to identify and treat the underlying cause
• Fluid resuscitation - infused crystalloid and/or blood products when available
• Electrolytes should be managed with nay massive transfusion - most common are hyperkalemia and hypocalcemia, both of which can lead to cardiac arrest.
• Assess fetal status - if fetus is dead or previable entire focus becomes optimal care of the mother. If fetus is alive and viable, maternal hemodynamic instability results in poor placental perfusion, and it is important to weigh maternal and fetal risks and benefits).
• Maintain oxygenation and perfusion - mechanical ventilation may be necessary

Question 27

Management of Delivery in DIC

Answer 27

• Hemodynamically stable mother with a viable fetus and reassuring fetal status - if mother is being resuscitated and is responding well and FHR tracing is normal, there is no need for deliver. In these cases, focus should be on treating the underlying cause.
• Hemodynamically stable mother with dead or unviable fetus - if fetus is dead or has poor prognosis (previable, kethal congenital abnormality, etc), then the goal is to reduce maternal morbidity and mortality risk. In most cases, this means avoiding C-section due to risk of uncontrollable hemorrhade.
  
  • Mother is supported with crystalloid, O₂, and blood products
  • Delivery is initiated since removal of conception products removes DIC trigger and causes myometrium to contract
• Hemodynamically unstable mother or fetal distress or contraindication to vaginal delivery
  
  • C-section is indicated. Depends on clincial judgement whether or not to try to improve clotting abnormality prior to c-section.

Question 28

Prognosis for Pregnancy DIC

Answer 28

• Maternal - most patients recover after delivery and treatment of coagulopathy
  
  • If due to acute fatty liver pregnancy resolution of DIC can take 4-5 days postpartum, since the liver is the source of most coagulation factors and site for D-dimer clearance.
  • Hsterectomy rates are high with 1/5 requiring hysterectomy to control bleeding
• Fetal/neonatal - survival depends on stage of pregnancy and placental function