HELLP Syndrome

OVERVIEW

• HELLP Syndrome: haemolysis, elevated liver enzymes, and a low platelet count
• there is clear overlap between pre-eclampsia and HELLP syndrome, and it is unclear whether the latter is a primary or secondary disease process.
• typically a third trimester condition, which may occur up to 7 days after delivery
• affects 05-1% pregnancies
• 1-2% mortality

DIAGNOSTIC CRITERIA

Tennessee Classification System diagnostic criteria for HELLP are:

• haemolysis
• increased LDH (> 600 U/L)
• increased AST (>or= 70 U/L)
• low platelets < 100 x 10(9)/L.

The HELLP syndrome may be complete or incomplete.

The Mississippi Triple-class HELLP System further classifies the disorder by the nadir platelet counts.

PATHOPHYSIOLOGY

Generalized endothelial and microvascular injury from

• activation of the complement and coagulation cascades
• increased vascular tone
• platelet aggregation

This results in areas of hemorrhage and necrosis within the liver and may evolve to large haematomas, capsular tears, and intraperitoneal bleeding.

CLINICAL FEATURES

History

• no ‘typical’ clinical symptoms
• epigastric or RUQ pain
• weight gain (oedema)

Examination

• hypertension
• tender RUQ
• oedema
• polyuria from nephrogenic DI

INVESTIGATIONS

• microangiopathic haemolytic anaemia (MAHA)
• elevated LFT’s – bilirubin, AST, ALT, LDH
• low platelets
• normal PT, APTT and coag screen
• haemolysis on blood film
• haptoglobins: low

COMPLICATIONS

Haemorrhage

• Abruptio placentae
• Severe postpartum haemorrhage
• Subcapsular liver haematoma
• Intracerebral or brainstem haemorrhage
• DIC

Infarction

• Liver infarct
• Cerebral infarct

Pregnancy

• overlap with pre-eclampsia
• preterm delivery
• foetal demise in utero

Other

• Visual impairment due to retinopathy
• Pulmonary oedema – higher risk in postpartum onset of HELLP
• Acute kidney injury – higher risk in postpartum onset of HELLP

DIFFERENTIAL DIAGNOSIS

• Pre-eclampsia / eclampsia
• Acute fatty liver of pregnancy
• Acute hepatitis
• HUS
• TTP (rare in pregnancy)
• ITP
• DIC (e.g. from PPH or amniotic fluid embolism)
• other causes of haemolysis (e.g. AIHA, sepsis)
• other causes of acute abdomen

MANAGEMENT

Resuscitation

• prepare for major haemorrhage
• major life threats are hepatic hemorrhage, subcapsular hematoma, liver rupture, and multi-organ failure

Specific treatment

• Delivery is indicated if the HELLP syndrome occurs after the 34th gestational week or the foetal and/or maternal conditions deteriorate.
• Seek and treat complications (e.g. APO, DIC, MODS)
• anti-hypertensives to keep BP below 155/105 mmHg
  — Labetolol or hydralazine or nifedipine
• MgSO4 IV for eclamptic seizure prophylaxis
• corticosteroids (IV)
  — no clear benefit for HELLP per se
  — given for fetal lung maturity from 24 to 34 weeks: either 2 doses of 12 mg betamethasone 24 hours apart or 6 mg dexamethasone 12 hours apart before delivery.
• Liver haemorrhage
  — manage conservatively where possible
  — correct coagulopathy
  — surgery includes drainage of the hematoma, packing, over-sewing of lacerations, or partial hepatectomy
  — consider arterial embolisation
• Exchange transfusion
  – considered in situations of progressive elevation of bilirubin or falling Hb or PLTs and ongoing deterioration in maternal condition.
• Novel therapies:
  — Antithrombin and glutathione  – have been trialed with some benefit demonstrated, but has not yet been subjected to any high quality trial
  — Octreotide – no role in HELLP syndrome
  — there are case reports of liver transplantation

Supportive care and monitoring

• consider invasive monitoring

Disposition

• OT or HDU/ ICU setting
• consider transfer to a liver transplant center

References and  Links

FOAM and web resources

• ICN — Hot Case #14 – I’m pregnant … HELLP!

Journal articles

• Haram K, Svendsen E, Abildgaard U. The HELLP syndrome: clinical issues and management. A Review. BMC Pregnancy Childbirth. 2009 Feb 26;9:8. PMC2654858.
• Lee NM, Brady CW. Liver disease in pregnancy. World J Gastroenterol. 2009 Feb 28;15(8):897-906. PMC2653411.
• McCrae KR. Thrombocytopenia in pregnancy. Hematology Am Soc Hematol Educ Program. 2010;2010:397-402. PMID: 21239825.
• Neligan PJ, Laffey JG. Clinical review: Special populations–critical illness and pregnancy. Crit Care. 2011 Aug 12;15(4):227. PMC3387584.
• Shames BD, Fernandez LA, Sollinger HW, Chin LT, D’Alessandro AM, Knechtle SJ, Lucey MR, Hafez R, Musat AI, Kalayoglu M. Liver transplantation for HELLP syndrome. Liver Transpl. 2005 Feb;11(2):224-8. PMID: 15666378.