Hypertensive Disorders in Pregnancy… HELLP!

Context

Pre-eclampsia is defined as:

• New onset hypertension after 20 weeks of gestation (systolic blood pressure > 140 and/or diastolic blood pressure > 90)

And either

• Proteinuria (urine protein:creatinine ratio 30mg/mmol)

Or

• Other features of pre-eclampsia¹:
  • AKI (creatinine 90)
  • Liver dysfunction (ALT>40)/epigastric/RUQ pain
  • New severe persistent headache without an alternative diagnosis
  • Persistent visual disturbance
  • Haematological complications (platelets <150/DIC/haemolysis)
  • Neurological complications (clonus/stroke/seizures(eclampsia))
  • Pulmonary oedema
  • Uteroplacental dysfunction (fetal growth restriction/placental abruption/intrauterine death)

Onset is usually after 20 weeks of gestation, but it can also occur up to a few weeks postpartum.

Eclampsia:

• This is pre-eclampsia that has progressed to cause seizure(s)

Learning bite

If new onset hypertension is associated with other features of pre-eclampsia, proteinuria does not necessarily need to be present.

Classification of Hypertensive Disorders of Pregnancy

Gestational hypertension:

This is new onset hypertension in pregnancy but where there is an absence of significant proteinuria and any other features of pre-eclampsia. Patients with gestational hypertension are at risk of going on to develop pre-eclampsia.

Chronic hypertension:

This may be previously diagnosed or recognised at the patients booking appointment. These patients are also at risk of going on to develop pre-eclampsia.

Learning bite

Both chronic hypertension and gestational hypertension increase the risk of pre-eclampsia.

• Pre-eclampsia is a pregnancy-specific multi-system disorder with unpredictable, variable and widespread clinical manifestations
• The pathophysiology is not clearly understood but the cause is thought to be multifactorial including genetic and immunological factors.
• It has been suggested that it originates in the placenta. It is thought to be associated with a failure of normal invasion of trophoblast cells, leading to maladaptation of maternal spiral arterioles (the source of blood supply to the fetus). This would explain why it can result in placental insufficiency and fetal growth restriction.
• It has also been suggested that a systemic maternal response causes vasoconstriction and increased capillary permeability, leading to hypertension and the other complications associated with pre-eclampsia.

Risk factors

There are multiple risk factors for pre-eclampsia²:

• Nulliparity
• Previous pre-eclampsia
• Family history pre-eclampsia
• Obesity (risk increases with increasing BMI)
• Extremes of maternal age (especially age > 40)
• Multiple pregnancy (e.g. twins)
• Subfertility
• Gestational hypertension
• Pre-existing diabetes mellitus
• Migraine
• Polycystic ovary syndrome (PCOS)
• Autoimmune disease (e.g. SLE or anti-phospholipid syndrome)
• Pre-existing renal disease
• Pre-existing cardiovascular disease and chronic hypertension
• Long interval between pregnancies (> 10 years)

Patients at risk of pre-eclampsia may be prescribed low dose aspirin from 12 weeks until delivery if they have a high-risk factor or more than 1 moderate risk factor for pre-eclampsia³:

Learning bite

Patients with hypertension in a previous pregnancy, chronic hypertension, chronic kidney disease, SLE/antiphospholipid syndrome, or diabetes mellitus are considered high risk of developing pre-eclampsia.

Clinical features

Clinical features of pre-eclampsia:

• Asymptomatic hypertension (picked up on screening or incidentally when presenting with another issue)
• Headache (usually frontal)
• RUQ or epigastric pain (also a symptom of HELLP syndrome)
• Nausea and vomiting
• Oedema (common but not specific). Especially if rapidly increasing and involving face and hands.
• Visual disturbance (flashing lights in the visual fields or scotomata)
• Shortness of breath (uncommon but can occur due to pulmonary oedema)
• Hyper-reflexia and/or clonus

Clinical features of eclampsia:

• Tonic-clonic seizures
  • often in the setting of known pre-eclampsia
  • can be at first presentation particularly if not engaged in antenatal care (only one third of women in the UK experiencing their first eclamptic seizure have established hypertension and proteinuria in the preceding week)

Learning bite

Many of the symptoms of pre-eclampsia are non-specific. Pregnant patients presenting with headache or gastritis-like symptoms should have pre-eclampsia considered in the differential.

Crises in pre-eclampsia:

• Acute kidney injury
• HELLP syndrome
• Placental abruption
• Pulmonary oedema (may be sudden onset and catastrophic)
• Transient left ventricular systolic or diastolic dysfunction
• Eclampsia
• Hepatic rupture
• DIC
• Haemorrhagic stroke
• Cortical blindness

Clinical features of HELLP syndrome: HELLP syndrome is a variant of severe pre-eclampsia characterised by haemolysis, elevated liver enzymes and low platelets.⁴

Symptoms and signs are similar to those of pre-eclampsia but also include jaundice and bleeding.

1. Haemolysis (H):
   • anaemia
   • dark urine
   • raised LDH (>600), raised bilirubin, schistocytes on blood film
2. Elevated liver enzymes (EL):
   • Epigastric/RUQ pain/tenderness
   • raised transaminases
   • abnormal clotting (prolonged PT)
3. Low platelets (LP):
   • Platelets < 100

Learning bite

HELLP syndrome is characterised by haemolysis, elevated liver enzymes and low platelets.

It would not be appropriate for all the recommended investigations for pre-eclampsia to be carried out within the emergency department, however there are some simple bedside tests and blood tests that can help to diagnose pre-eclampsia and assess for complications. Referral should be made to obstetrics for specialist management.

• Blood pressure monitoring repeated to confirm (with correct BP cuff size)
• Blood tests
• Full blood count (looking specifically at platelets)
• Renal function (risk of AKI)
• Liver function tests (risk of HELLP syndrome – haemolysis, elevated liver enzymes, low platelets)

Also consider:

• blood film (risk of haemolysis and micro-angiopathic haemolytic anaemia)
• clotting screen (if thrombocytopaenic)

• Urine
• Urinalysis looking for protein (preferably use an automated reader as this is more accurate); 1+ or more of protein is significant.
• If 1+ or more of protein is present on urinalysis, send urine for protein:creatinine ratio (30mg/mmol confirms proteinuria) or albumin creatinine ratio (>8mg/mmol significant)

After referral to obstetrics, further tests will be arranged to assess fetal wellbeing:

• Cardiotocography (CTG)
• Ultrasound (for fetal growth, umbilical artery doppler and amniotic fluid index)

Learning bite

Initial investigations in the ED for possible pre-eclampsia include blood pressure measurement, urinalysis and blood tests (FBC, U+E, and LFTs).

Recognition of Severe Features of Pre-eclampsia

Severe features of pre-eclampsia include severe hypertension with significant proteinuria or hypertension with other severe features of pre-eclampsia.

Severe hypertension:

• SBP 160 and/or DBP 110 (with significant proteinuria)

Other severe clinical features of pre-eclampsia³:

• Ongoing or recurring severe headaches
• Visual scotomata
• Nausea or vomiting
• Epigastric pain
• Oliguria and severe hypertension

Other features:

• Abnormal blood tests (e.g. rising creatinine, transaminases or falling platelets)
• Abnormal ultrasound (fetal growth restriction or abnormal umbilical artery doppler)

Learning bite

Severe pre-eclampsia is diagnosed when there is persistent hypertension above 160 systolic and/or 110 diastolic associated with significant proteinuria or other features of severe pre-eclampsia. Severe hypertension requires immediate antihypertensive treatment to reduce the risk of haemorrhagic stroke.

The differential diagnosis will differ depending on the presenting symptoms/signs.²

Learning bite

There is a wide differential diagnosis for pre-eclampsia that needs to be considered to prevent other serious diagnoses being missed.

ED Management of Pre-eclampsia:

• Contact obstetrics early
• Severe hypertension in pregnancy SBP 160 or DBP 110 requires urgent antihypertensive therapy in a monitored setting
• BP management:
  • Labetalol first line unless unsuitable or contraindicated³ (e.g. asthma)
  • Nifedipine MR second line
  • Methyldopa third line (not used postpartum due to risk of depression)
• Careful fluid balance monitoring
  • Fluid restriction to reduce the risk of pulmonary oedema
  • Monitor urine output if severe
• Consider IV magnesium sulphate for eclampsia prophylaxis if severe features of pre-eclampsia

Definitive management:

Definitive management of pre-eclampsia is ultimately delivery of the fetus. Timing of delivery will be decided by senior members of the obstetric team according to the severity of pre-eclampsia, the current gestation and in consultation with the patient. Following diagnosis of pre-eclampsia, the majority of women are managed as inpatients until delivery.

Learning bite

For management of severe hypertension in pregnancy, follow local guidelines. An oral antihypertensive may be given initially (nifedipine MR 10mg or labetalol 200mg) followed by IV labetalol or IV hydralazine if adequate BP control is not achieved.¹

ED Management of Eclampsia:

• Ask for help early from ITU and obstetric teams
• ABC approach, manage in left lateral position
• Airway and breathing assessment with high flow oxygen
• If inadequate ventilation, consider early intubation (laryngeal oedema in pre-eclampsia and increased risk of aspiration in pregnancy)
• Magnesium sulphate IV is treatment of choice for seizures 4g loading dose over 5-10 mins then 1g/hr infusion for 24 hours
• Further 2g boluses of magnesium sulphate can be given if further seizures occur after initial loading.³
• Patients will need to be managed in HDU/ITU to stabilise blood pressure prior to delivery

Pitfall

If a patient is presumed to have eclampsia but is not responding to repeated boluses of magnesium sulphate, commence an anti-epileptic and consider alternative diagnoses. If not known to have epilepsy and no strong evidence that seizure is eclamptic, will need neuroimaging with CT head and/or MRV to look for other diagnoses including venous sinus thrombosis.

Learning bite

Eclampsia should be considered in all women presenting with a seizure after 20 weeks gestation or in the postpartum period. Unless a seizure can be clearly attributed to epilepsy, magnesium sulphate should be commenced.

References

1. Magee LA, Brown MA, et al. The 2021 International Society for the Study of Hypertension in Pregnancy classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2022 Mar;27:148-169.
2. BMJ Best Practice, Pre-eclampsia. Last updated: 21 Mar 2024
3. National Institute for Health and Care Excellence (NICE) Hypertension in pregnancy: diagnosis and management. NG [133] 2019. Last updated: 17 April 2023
4. BMJ Best Practice, HELLP Syndrome. Last updated: 08 Feb 2024

Additional resources

Impey L, Child T. Obstetrics and Gynaecology, 4Th Edition. John Wiley & Sons, 2012. p.166.