syndrome HELLP

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.

Étiologie

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

Épidémiologie³

• 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).

Facteurs de risque^{1 2}

• Age >35.

• Nulliparité.

• Previous gestational hypertension.

• Grossesse multiple.

• Previous HELLP syndrome.

• Caucasian racial origin.

• Antiphospholipid syndrome (APS) - 10.5% of patients with HELLP syndrome have APS.⁴

Présentation³

• 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.

Enquêtes³

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.

Diagnostic différentiel

• Acute fatty liver of pregnancy.

• Thrombotic thrombocytopenic purpura (TTP).

• Immune thrombocytopenia (ITP).

• Syndrome hémolytique et urémique.

• Acute exacerbation of lupus érythémateux systémique.

• Viral hepatitis.

• Cholangitis.

Gestion³

• 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 pour plus de détails.

• 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.

Pronostic

• If HELLP syndrome is not treated early, up to 25% of women may develop serious complications.

• Without treatment there is a significant mortality.

• The mortality rate among babies born to mothers with HELLP syndrome varies and depends mainly on gestation and birth weight.

Complications³

Maternelle :

• Eclampsia - 4-9%.

• Décollement placentaire- 9-20%.

• Coagulation intravasculaire disséminée (CID) - 5-56%.

• Lésion rénale aiguë - 7-36%.

• Severe ascites - 4-11%.

• Cerebral oedema - 1-8%.

• Œdème pulmonaire - 3-10%.

• Wound infection (after caesarean) - 7-14%.

• Liver rupture.

• Décollement de la rétine and other eye problems may occur.

• Cerebral haemorrhage or stroke.

• Death - 1-25%.

Fetal:

• Perinatal death - 7-34% depending on gestational age.

• Retard de croissance intra-utérin - 38-61%.

• Preterm delivery - 70% (15% <28 weeks of gestation).

• Neonatal thrombocytopenia - 15-38%.

Prévention

• 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.