HELLP syndrome

HELLP syndrome is a complication of pregnancy which usually presents in women

who have pre-eclampsia or eclampsia. Affected women also show signs of liver
damage and abnormalities in blood clotting.
It is characterised by:
 Haemolysis (H)
 Elevated Liver enzymes (EL)
 Low Platelet count (LP)
NB: most isolated cases of thrombocytopenia in pregnancy are due to gestational
thrombocytopenia, where the platelet count falls to 7-150 x 109/L, often late in the
second or in the third trimester, rather than due to HELLP syndrome.
Aetiology
The cause of HELLP syndrome is unknown but it is a disorder of the placenta that
shares histopathological, placental morphological features and changes in gene
expression with early-onset pre-eclampsia.[1] There is still debate as to whether it is a
severe form of pre-eclampsia or a separate disease entity. An incomplete form, where
there is no haemolysis, is also described (ELLP syndrome).[2]
Epidemiology[3]
 HELLP syndrome occurs in 0.5 to 0.9% of all pregnancies and in 10-20% of
cases with severe pre-eclampsia.
 HELLP syndrome may occur after pre-eclampsia is diagnosed (the norm) or
be the first warning of pre-eclampsia when misdiagnosed as, for example,
hepatitis or thrombotic thrombocytopenic purpura (TTP).
Risk factors[1, 2]
 Age >35.
 Nulliparity.
 Previous gestational hypertension.
 Multiple pregnancy.
 Previous HELLP syndrome.
 Caucasian racial origin.
 Antiphospholipid syndrome (APS) - 10.5% of patients with HELLP syndrome
have APS.[4]

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Presentation[3]
 HELLP syndrome is a serious complication of pregnancy and may present at
any time in the last half of pregnancy.
 70% of cases present before delivery, peaking between 27 and 37 weeks of
gestation but it can occur earlier or later.
 30% of women with HELLP syndrome present postpartum, usually within 48
hours of delivery.
 Symptoms of HELLP syndrome are usually nonspecific.
 Onset is usually rapid.
 Headache is reported in up to 30-60% of women and visual symptoms in 20%.
 Initially, women may report nonspecific symptoms including malaise, fatigue,
right upper quadrant or epigastric pain, nausea, vomiting, or flu-like
symptoms.
 The symptoms of HELLP syndrome are characterised by exacerbation of
symptoms at night and relief during the day.
 Hepatomegaly can occur.
 Some women may have easy bruising/purpura.
 On examination, oedema, hypertension and proteinuria are present.
 Tenderness over the liver can occur.
Investigations[3]
There needs to be a high index of clinical suspicion in order to avoid diagnostic delay
and improve outcome.
 Haemolysis with fragmented red cells on the blood film, due to
microangiopathic haemolytic anaemia.
 Raised LDH >600 IU/L with a raised bilirubin, due to the destruction of red
blood cells.
 Liver enzymes are raised with an AST or ALT level of >70 IU/L, due to liver
injury.
 Platelets <100 x 109/L due to activation and increased consumption.
 Levels associated with increased maternal morbidity and mortality are:
 AST or ALT >150 IU/L.
 LDH >1400 U/L.
 Uric acid >7.8 mg/100 ml (>460 µmol/L).
 Plasma glutathione S-transferase-a1 (α-GST or GST-a1) is a very sensitive
marker for early liver damage but is not widely available.

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Differential diagnosis
 Acute fatty liver of pregnancy.
 Thrombotic thrombocytopenic purpura (TTP).
 Immune thrombocytopenia (ITP).
 Haemolytic uraemic syndrome.
 Acute exacerbation of systemic lupus erythematosus.
 Viral hepatitis.
 Cholangitis.
Management[3]
 Definitive treatment of HELLP syndrome requires delivery of the fetus and is
advised after 34 weeks of gestation if multisystem disease is present.
 A case control study which included 129 women with HELLP, showed no
differences in severe maternal morbidity or major neonatal complications
between those women who had their delivery planned within 48 hours and
those with a planned immediate delivery, suggesting that a short delay in
delivery can be considered.[2]
 There is no clear evidence of any effect of giving corticosteroids on clinical
outcomes for women with HELLP syndrome.[5]
 If the fetus is less than 34 weeks of gestation and delivery can be deferred,
corticosteroids should be given to promote fetal lung maturation. See
separate Premature Labour article for more details.
 In the UK the National Institute for Health and Care Excellence (NICE)
recommends that magnesium sulfate should be considered but that neither
dexamethasone nor betamethasone should be used in the treatment of HELLP.
[6]

 Transfusion of red cells, platelets, fresh frozen plasma and cryoprecipitate or

fibrinogen concentrate are required as indicated clinically and by blood and
coagulation tests.
 Postpartum HELLP syndrome may be treated with plasma exchange.
 Blood pressure control is essential.
 Women with severe liver damage may need liver transplantation.
Prognosis
 If HELLP syndrome is not treated early, up to 25% of women may develop
serious complications.
 Without treatment there is a significant mortality.

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Complications[3]
Maternal:
 Eclampsia - 4-9%.
 Placental abruption- 9-20%.
 Disseminated intravascular coagulation (DIC) - 5-56%.
 Acute kidney injury - 7-36%.
 Severe ascites - 4-11%.
 Cerebral oedema - 1-8%.
 Pulmonary oedema - 3-10%.
 Wound infection (after caesarean) - 7-14%.
 Liver rupture.
 Retinal detachment and other eye problems may occur.
 Cerebral haemorrhage or stroke.
 Death - 1-25%.
Fetal:
 Perinatal death - 7-34% depending on gestational age.
 Intrauterine growth restriction - 38-61%.
 Preterm delivery - 70% (15% <28 weeks of gestation).
 Neonatal thrombocytopenia - 15-38%.
Prevention
 No studies have been specifically designed to assess the ability of aspirin to
prevent HELLP syndrome.
 There is no proven treatment or prophylaxis for HELLP syndrome. However,
due to its high morbidity and mortality, being able to predict those women at
highest risk of developing it could have an impact on outcomes.
 There is some evidence that using a combination of biochemical and
biophysical markers and risk factors in the first trimester can predict HELLP
syndrome.[1]
 Any woman who has had HELLP syndrome should be screened for
antiphospholipid syndrome.
 Oral contraceptives are safe in women who have previously had HELLP
syndrome, although more effective forms of contraception may be indicated.

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References
1. Oliveira N, Poon LC, Nicolaides KH, et al; First trimester prediction of
HELLP syndrome. Prenat Diagn. 2016 Jan36(1):29-33. doi: 10.1002/pd.4694.
Epub 2015 Nov 22.
2. Fitzpatrick KE, Hinshaw K, Kurinczuk JJ, et al; Risk factors, management,
and outcomes of hemolysis, elevated liver enzymes, and low platelets
syndrome and elevated liver enzymes, low platelets syndrome. Obstet
Gynecol. 2014 Mar123(3):618-27. doi: 10.1097/AOG.0000000000000140.
3. Haram K, Svendsen E, Abildgaard U; The HELLP syndrome: clinical issues
and management. A Review. BMC Pregnancy Childbirth. 2009 Feb 269:8.
4. Tufano A, Coppola A, Maruotti GM, et al; HELLP syndrome and its relation
with the antiphospholipid syndrome. Blood Transfus. 2014 Jan12(1):114-8.
doi: 10.2450/2013.0154-13. Epub 2013 Nov 15.
5. Woudstra DM, Chandra S, Hofmeyr GJ, et al; Corticosteroids for HELLP
(hemolysis, elevated liver enzymes, low platelets) syndrome in pregnancy.
Cochrane Database Syst Rev. 2010 Sep 8(9):CD008148. doi:
10.1002/14651858.CD008148.pub2.
6. Hypertension in pregnancy; NICE Clinical Guideline (August 2010, updated
2011)