Question 28

A 20-year-old primigravida presents at 37 weeks gestation with jaundice, headache, blurred vision and hypertension (140/90 mmHg). The antenatal period was otherwise unremarkable. She is febrile, drowsy, pale, icteric and has pedal oedema. The uterus is palpated as for a full term pregnancy with a normal CTG trace. Examination is otherwise normal.

The following are her early blood results:

Parameter	Patient Value	Normal Adult Range
Hb	80 G/L*	115 – 160
Platelets	52 x 109/L*	140 – 400
International Normalised Ratio	1.8*	0.9 – 1.3
Activated Partial Thromboplastin Time	55 seconds*	25 – 38
Lactate Dehydrogenase	654 U/L*	110 – 250
Fibrinogen	1.0 G/L*	1.5 – 4.0
Total Bilirubin	51 micromol/L*	< 20
Urea	30 mmol/L*	3 – 8
Creatinine	298 micromol/L*	70 – 120
Potassium	5.1 mmol/L*	3.2 – 4.5

a) List four likely diagnoses for this clinical presentation.

b) For each of your differential diagnoses:

List the important management interventions.
List one additional diagnostic test.

[Click here to toggle visibility of the answers]

College Answer

Pre-eclampsia
HELLP Syndrome
Sepsis with DIC
HUS-TTP
Acute fatty liver of pregnancy

b)
Pre-eclampsia

Deliver baby
Control BP
- Hydralazine, beta blockers
- SNP/GTN if intravenous agent required.
Prevention of seizures
Magnesium sulphate
Urinalysis – protein, WBCs, RBCs, casts
Evidence of infection or proteinuria (pre-eclampsia)
Renal US

HELLP Syndrome

Deliver baby
Regular monitoring of platelet count and liver function
Supportive measures whilst observing in HDU for dangerous complications
- hepatic haemorrhage/rupture, progressive renal failure, pulmonary oedema.
Peripheral blood film smear
Reticulocyte count, haptoglobins, conjugated/unconjugated bilirubin
Haemolysis screen
Full liver function tests

Sepsis with DIC

Timely delivery of baby in consultation with obstetrician.
Early broad-spectrum antibiotics.
Cardiovascular support – adequate volume resuscitation and establish MAP > 65mmHg.
Blood, sputum, urine and vaginal swab for MC&S
Septic screen

HUS-TTP

Deliver the baby.
Fresh frozen plasma
Therapeutic plasma exchange
Corticosteroid therapy
Monoclonal antibody therapy – Rituximab
Evidence of haemolysis or MAHA
Reticulocyte count, haptoglobins, conjugated/unconjugated bilirubin
Haemolysis screen
ADAMTS 13

Acute fatty liver of pregnancy

Timely delivery of baby once mother stabilised
Correction of DIC
Supportive therapy
Monitoring and treatment of complications post delivery e.g. pancreatitis
Consideration for liver transplantation in with irreversible severe liver failure despite delivery and aggressive supportive care
Full set liver function tests
BSL
Liver US
Evidence of haemolysis or MAHA
Reticulocyte count, haptoglobins, conjugated/unconjugated bilirubin
Haemolysis screen

Discussion

This question closely resembles Question 6 from the first paper of 2010.

The college has yielded five differentials, each of which deserve a whole chapter dedicated to them.

Pre-eclampsia
HELLP Syndrome
Sepsis with DIC
HUS-TTP
Acute fatty liver of pregnancy

There is little to add to the sufficently detailed yet concise college answer.

One must remember that in most of these conditions, the key step is to deliver the baby.

The one critical investigations for each differential would be...

Pre-eclampsia - urinary protein
HELLP Syndrome - hemolytic screen
Sepsis with DIC - septic screen
HUS-TTP - ADAMTS13 test
Acute fatty liver of pregnancy - ultrasound to rule out hepatic rupture

A more complete list:

Acute Liver Failure in Pregnancy
Cause	Diagnostic features	Notes and management options
Causes of liver failure which are unrelated to pregnancy
Drug-induced hepatitis	Paracetamol level	N-acetylcysteine crosses the placenta and has a protective effect in the foetus (Horowitz et al, 1997)
Shock, haemorrhage	Ultrasound: structurally normal liver	The LFT derangement which follows resuscitation for severe postpartum haemorrhage Should improve after the shock state has resolved
Decompensation of pre-existing liver disease	Ultrasound: cirrhosis	Risk of preterm delivery and peripartum complications is increased (Aggarwal et al, 1999) Normal management of the cirrhotic patient applies
Causes of liver failure which are exacerbated by pregnancy
Viral hepatitis	Hep B and C serology	Most common cause of LFT derangement in pregnancy B and C are the most common usually, BP is normal (in contrast with HELLP) Ribavirin is contraindicated (a teratogen) Other antiviral drugs may still be useful to decrease the viral load preior to delivery (to protect the baby from vertical transmission)
Portal vein thrombosis	Ultrasound: portal vein occlusion on Doppler	Due to hypercoagulable state of pregnancy Heparin infusion is the standard of care Generally, TIPS procedure is too technically difficult in pregnancy - but that is another option
Hepatic venous thrombosis	Ultrasound: hepatic vein occlusion on Doppler
Cholecystitis	Ultrasound: thickened gall bladder wall, stones LFTs: cholestatic picture	Conservative antibiotic therapy is best Non-emergency surgery has better outcomes, i.e. it pays to delay until the acute flare has passed (Casey et al, 1996)
Pregnancy-related causes of liver failure
Hyperemesis gravidarum	LFTs: "transaminitis"	Unlike the others, this is a feature mainly of the first trimester It is associated with raised transaminases, as opposed to liver failure per se - synthetic function is preserved (Outlaw et al, 2000) Antiemetics and supportive care are the only options
Intrahepatic cholestasis of pregnancy (icterus gravidarum)	History of jaundice and pruritis LFTs: cholestatic picture Ultrasound: gall bladder looks normal	Pruritis is usually the patient's greatest concern. Can be managed with ursodeoxycholic acid. Resolves rapidly with delivery Will occur again in the next pregnancy in 60%
Pre-eclampsia	Proteinuria, hypertension, oedema, visual disturbance, etc. See the local chapter.	LFT derangement is due to fibrin deposition and endothelial dysfunction in the sinusoids. Typically, this is also not "liver failure" but rather an LFt derangement of unclear significance (Munazza et al, 2013) Standard therapy applies: antihypertensives, magnesium sulfate, and urgent delivery
HELLP	Thrombocytopenia Low haptoglobin Raised LDH, Uncojugated bilirubin Blood film features of haemolysis See the local chapter.	Delivery is the treatment Some authors recommend corticosteroids (Guntupalli et al, 2005) but only as a means of helping foetal lung maturation Thrombocytopenia and LFT derangement will continue for up to 48 hours postpartum Standard therapy applies: antihypertensives, magnesium sulfate, urgent delivery, correction of coagulopathy
Acute fatty liver of pregnancy	Presents with abdominal pain, vomiting, hypoglycaemia, coagulopathy Characteristic ultrasound findings of the liver parenchyma	18% maternal mortality, 2% foetal mortality (Guntupalli et al, 2005) Liver failure is present, not just LFT derangement Delivery fixes everything, as in HELLP Fulminant liver failure may be present by then, and liver transplant may be the only option
Acute hepatic rupture	Ultrasound: haematoma Haemodynamic instability and haemorrhagic shock Abdominal pain (RUQ) Haemoperitoneum	Maternal mortality is around 30% (Manas et al, 1985) If it has not ruptured (i.e. only a subcapsular haematoma) then conservative management and urgent dleivery are probably safe Surgical packing and/or angioembolisation may be the only options
Other causes of febrile jaundiced coma with thrombocytopenia
TTP/HUS	Pentad: thrombocytopenia, microangiopathic haemolytic anemia, neurologic abnormalities, renal failure, and fever. See local chapter. Low ADAMTS-13 levels are found.	The SAQs often give a picture which could be consistent with TTP. It actually does occur often in pregnancy and the postpartum period (McMinn et al, 2001) "How is this not HELLP?" one might ask. Well: HELLP is never in the first trimester HELLP always resolves following delivery I.e. if after delivery the abnormalities persist, plasmapheresis becomes a serious option.
Sepsis with DIC	Bacteraemia Haemodynamic instability, hypotension	read all about the difficulties of making the diagnosis of sepsis in pregnancy

References

The UpToDate links for the college's differentials are here:

[Submit a comment or correction]