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HELLP syndrome is a clinical syndrome that develops in pregnancy characterized by the triad of:

Haemolysis, Elevated Liver enzymes, and a Low Platelet count

HELLP syndrome is a clinical syndrome that develops in pregnancy characterized by the triad of:

  • H       Haemolysis (with microangiopathic blood smear)
  • EL      Elevated Liver enzymes
  • LP      Low Platelets

Signs and symptoms typically develop between 28 and 36 weeks of gestation, however second trimester or postpartum onset can also occur.

There is no “typical” clinical presentation for patients with HELLP syndrome, and so its diagnosis is based upon the presence of all of the laboratory abnormalities comprising its name (hemolysis with a microangiopathic blood smear, elevated liver enzymes, and low platelet count) in a pregnant woman.

HELLP syndrome probably represents a severe form of preeclampsia however the exact relationship between the two disorders remains controversial.

As many as 15 – 20 % of patients with HELLP syndrome do not have antecedent hypertension or proteinuria, leading some authorities to believe that HELLP is a distinct disorder from preeclampsia.

Both preeclampsia with severe features and HELLP syndrome may be associated with serious complications including hepatic manifestations, such as infarction, hemorrhage, and rupture.

Following delivery, (the only definitive therapy) maternal symptoms and signs usually begin to improve within 48 hours, but a protracted course is possible.

The outcome for mothers with HELLP is generally good, however, serious complications are relatively common.

History

HELLP syndrome was first described as a distinct clinical entity (as opposed to severe pre-eclampsia) by Dr. Louis Weinstein in 1982 1

Epidemiology

HELLP Syndrome affects up to 1% pregnancies.

It is, however, seen in around 10 – 20 % of pregnancies with severe preeclampsia / eclampsia.

Mortality is around 1 – 2%

Pathophysiology

HELLP syndrome probably represents a severe form of preeclampsia however the exact relationship between the two disorders remains controversial.

As many as 15 – 20 % of patients with HELLP syndrome do not have antecedent hypertension or proteinuria, leading some authorities to believe that HELLP is a distinct disorder from preeclampsia.

The exact pathogenesis of HELLP syndrome is unknown.

If it is a form of severe preeclampsia, it likely originates from aberrant placental development and function.

As an independent entity, it has been attributed to abnormal placentation, similar to preeclampsia, but with greater hepatic inflammation and greater activation of the coagulation system than in preeclampsia

Risk Factors:
  1. A previous history of HELLP
  2. A previous history of preeclampsia
  3. Genetic variants

Note that in contrast to preeclampsia, nulliparity is not a risk factor for HELLP syndrome, as half or more of affected patients are multiparous.
Of those women who develop HELLP, in a subsequent pregnancy:

  • 7 % develop HELLP again.
  • 18 % develop preeclampsia
  • 18 % develop gestational hypertension.

Clinical features

There is no “typical” clinical presentation for patients with HELLP syndrome, and so the diagnosis of HELLP syndrome is based upon the presence of all of the laboratory abnormalities comprising its name (hemolysis with a microangiopathic blood smear, elevated liver enzymes, and low platelet count) in a pregnant woman.

Signs and symptoms typically develop between 28 and 36 weeks of gestation, however second trimester or postpartum onset can also occur.

In one illustrative series (of 442 patients) HELLP syndrome, occurred: 3

  1. Prior to delivery in 70 % of cases:
    • Of these patients, approximately 80 % were diagnosed prior to 37 weeks of gestation
    • Fewer than 3 % developed the disease between 17 – 20 weeks of gestation.
  2. Postpartum in 30 % of cases:
    • These cases were usually within 48 hours of delivery, but as long as 7 days after birth.
Clinical history:
  1. Headache (reported rates vary from 33 – 61 % of cases)
  2. Nausea / vomiting (reported rates vary from 29 – 84 % of cases)
  3. Malaise
  4. Visual disturbances (reported rates vary from 10 – 20 % of cases)
  5. Right upper quadrant pain / epigastric (reported rates vary from 40 – 90 % of cases)
Examination:
  1. Hypertension (reported rates vary from 82 – 88 % of cases)
  2. Right upper quadrant / epigastric tenderness (reported rates vary from 40 – 90 % of cases)
  3. Jaundice (reported rates are around 5 % of cases)
  4. Proteinuria (reported rates vary from 86 – 100 % of cases)

Diagnostic criteria

HELLP syndrome is a clinical syndrome that develops in pregnancy characterized by the triad of:

H:        Hemolysis: with a microangiopathic blood smear
EL:      Elevated Liver enzymes
LP:      Low Platelets

Specific diagnostic criteria are described by the Tennessee classification as follows:

  • Microangiopathic haemolytic anaemia
    • Blood film shows characteristic schistocytes.
    • Other signs suggestive of hemolysis include an elevated indirect bilirubin level and a low serum haptoglobin concentration (≤ 25 mg/dL).
  • Platelet count ≤ 100,000 cells/microL.
  • Total bilirubin ≥ 20.52 micromol/L (or  ≥ 1.2 mg/dL).
  • Serum AST > 2 times upper limit of normal for local laboratory (this is usually > 70 IU/L.)

Some clinicians use alanine aminotransferase (ALT) levels instead of, or in addition to, AST levels. An advantage of the AST is that it is a single test that reflects both hepatocellular necrosis and red cell hemolysis.

Note that women who do not meet all of the above laboratory abnormalities are considered to have partial HELLP syndrome. These patients may however progress to a complete expression of the HELLP syndrome.

Complications

Serious maternal morbidity may be present at initial presentation or may develop shortly thereafter.

The risk of serious morbidity correlates with increasing severity of maternal symptoms and laboratory abnormalities

Serious complications can include:

  1. Anaemia
  2. Disseminated intravascular coagulation (DIC) (around 20%)
  3. Abruptio placentae (around 16%)
  4. Acute renal failure (around 8%).
  5. Bleeding:
    • Subcapsular or intraparenchymal liver hematoma (around 1%).
    • Intracerebral hemorrhage
    • Bleeding related to thrombocytopenia, including severe postpartum haemorrhage
  6. Pulmonary edema/ ARDS (around 6%).
  7. Hepatic:
    • Liver impairment/ failure
    • Liver infarcts
    • Hepatic rupture / bleeding
  8. Retinopathy:
    • Retinal detachment (around 1%).
  9. Fetal:
    • Fetal/neonatal and long-term prognosis are most strongly associated with gestational age at delivery and birth weight.
    • Maternal laboratory parameters do not predict fetal mortality.
    • Adverse fetal effects include:
      • Premature delivery 
      • Intrauterine growth restriction / FDIU

Differential Diagnoses

The principle differential diagnoses will include: 

  1. Pre-eclampsia / eclampsia (assuming that HELLP syndrome is a distinct entity from these)
  2. Acute fatty liver of pregnancy:
    • Clinical presentation commonly includes nausea and vomiting, abdominal pain, malaise, polydipsia/polyuria, jaundice/dark urine, encephalopathy, and hypertension/preeclampsia.
    • Severe hypoglycaemia is also a characteristic feature
    • HELLP may be difficult to distinguish clinically from AFLP since both occur at the same time in gestation and share several clinical features. It is important to differentiate between the two disorders because women with AFLP can rapidly develop liver failure and encephalopathy.
    • Additional laboratory testing can be helpful: prolongation of the prothrombin (PT) and activated partial thromboplastin time (aPTT), severe hypoglycemia, and elevated creatinine concentration are more common in women with AFLP than in those with HELLP.
    • Hypertension is more common in HELLP than in AFLP
  3. Acute viral hepatitis
  4. Other liver disease unrelated to pregnancy.
  5. Haematological conditions: 
    • HUS:
      • Severe renal insufficiency is suggestive of haemolytic uremic syndrome (HUS), which may be caused by a Shiga toxin-producing organism, complement regulatory defect (inherited or acquired), or a drug effect.
    • TTP (rare in pregnancy):
      • A high LDH level with only modest elevation of AST is more consistent with TTP than HELLP.
      • The percentage of schistocytes on peripheral smear is often higher in TTP (2 – 5 %) than in HELLP (< 1 %).
    • DIC: prolongation of the PT and aPTT, and reductions in the plasma concentrations of factors V and VIII.
  6. Conditions causing Right upper quadrant / epigastric pain in general:
    • Right upper quadrant / epigastric pain may mimicmany common non- obstetric conditions such as biliary colic/ cholecystitis or lower lobe lung conditions (pneumonia or pulmonary embolism)
    • These can of course all occur in pregnancy, however in any pregnant patient there must always be high index of suspicion for a pregnancy related condition – such as abruption, splenic artery aneurysm rupture, preeclampsia / eclampsia or HELLP

A correct diagnosis is vital, as “empiric” treatments may be contraindicated and dangerous, anticoagulation for suspected PE for example is contraindicated and dangerous in all of these pregnancy related conditions.          

Investigations

Blood tests:

  1. FBE:
    • Anaemia (from hemolysis)hrombocytopenia
    • Typical blood smear: micro-angiopathic haemolytic anaemia, evidenced by RBC fragmentation, (schistocytes) which can be seen on the peripheral blood film.
  2. U&Es/ glucose
  3. LTTs
  4. Coagulation profile: normal PT and aPTT (unless there is a superimposed DIC)
  5. LDH: increased > 600 U/L (elevated LDH is a non-specific finding associated with both hemolysis and liver disease in general)
  6. Blood group and save (or cross match, as clinically indicated).

CXR:

For any respiratory symptoms

Ultrasound:

  • Fetal well being
  • Abruptio placentae
  • Abdominal free fluid: subcapsular or intraparenchymal liver hematoma/ liver hemorrhage

CTG Monitoring:

To assess fetal wellbeing.

CT / MRI Scan:

Computed tomography (or magnetic resonance imaging) may be necessary when significant complications such as hepatic infarction, hematoma, or rupture are suspected because of sudden severe right upper quadrant abdominal pain.  These may be associated with shoulder pain, neck pain, and/or hypotension.

CT (or MRI) is more reliable than ultrasonography for detecting these lesions

Management

In general terms, management is along similar lines as for pre-eclampsia/ eclampsia.

Following delivery, maternal symptoms and signs usually begin to improve within 48 hours, but a protracted course is possible.

The outcome for mothers with HELLP is generally good, however, serious complications are relatively common.

From an ED perspective the major immediate life threats are:

  • Hepatic hemorrhage / subcapsular hematoma / liver rupture
  • Multi-organ failure

In general terms management involves the following:

1.  Immediate attention to any ABC issues

2. Hypertension, (if present):

  • The approach to antihypertensive therapy is the same as that for preeclampsia
  • Oral antihypertensive drugs:
    • Oral antihypertensive drugs are mandatory for systolic blood pressure ≥ 170 mm Hg or diastolic pressure ≥ 110 mm Hg, although lower thresholds are advisable if signs or symptoms are present.
    • Options include:
      • Labetolol
      • Methyldopa
      • Nifedipine SR
      • The two most commonly used IV options are:
        • IV labetalol: Intravenous labetalol is now considered to be the primary drug of choice for the urgent control of severe hypertension in pregnancy.
        • IV hydralazine: may be considered for women with a contraindication to IV beta blockers such as a history of significant asthma or congestive heart failure. Classified as class C during pregnancy.

3. MgSO4 IV for eclamptic seizure prophylaxis

4. Corticosteroids (IV)

  • These have no clear benefit for HELLP syndrome itself.
  • They may be given for enhancing fetal lung maturity from 24 – 34 weeks:
    • 2 doses of 12 mg betamethasone 24 hours apart
      Or
    • 6 mg dexamethasone 12 hours apart before delivery.

5. Blood products:

  • Blood transfusion may be required for clinically significant anaemia or where there is intra-abdominal bleeding.   
  • Platelets:
    • Actively bleeding patients with thrombocytopenia should be transfused with platelets.
    • Platelet transfusion may be indicated to prevent excessive bleeding during delivery if the platelet count is less than 20,000 cells/microL, but the threshold for prophylactic platelet transfusion in this setting is controversial and there should be haematology consultation. 

6. Liver haemorrhage:

  • This is usually managed conservatively where possible.
  • Correct any coagulopathy
  • Surgical options include:
    • Drainage of the hematoma
    • Packing / oversewing of lacerations, or partial hepatectomy
  • Arterial embolisation may also be considered in patients who are who are relatively hemodynamically stable

7. Delivery:

Delivery (either by vaginal delivery or cesarean section) is indicated if the HELLP syndrome occurs after the 34th gestational week or the foetal and/or maternal condition deteriorates.

At 24 – 34 weeks’ gestation and a stable mother and fetus, administration of steroids and a wait of 24 – 48 hours may be considered. After this time a re-evaluation is made for delivery based on the maternal-fetal condition.

Prevention

There is no current evidence that any therapy prevents recurrent HELLP syndrome.

Disposition

As soon as the diagnosis is suspected consultation/ referral should be made urgently to the Obstetric Unit.

Frequently these will be also be need for consultation with:

  • Haematology Unit
  • ICU
  • Paediatrics

References

FOAMed

Publications

Fellowship Notes

Dr Jessica Hiller LITFL Author

Doctor at Sir Charles Gairdner Hospital in Western Australia. Graduated from Curtin University in 2023 with a Bachelor of Medicine, Bachelor of Surgery. I am passionate about Obstetrics and Gynaecology, with a special interest in rural health care.

Physician in training. German translator and lover of medical history.

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