HELLP syndrome

What is HELLP syndrome

HELLP syndrome is a group of symptoms that occur in pregnant women who have:

  • HHemolysis. This is the breakdown of red blood cells. Red blood cells carry oxygen from your lungs to the rest of your body.
  • ELElevated liver enzymes. High levels of these chemicals can be a sign of liver problems.
  • LPLow platelet count. Platelets help the blood clot.

Some pregnant women with high blood pressure develop HELLP syndrome.

HELLP syndrome is rare but serious. HELLP syndrome happens in about 1 to 2 of 1,000 pregnancies. About 1-2 in 10 pregnant women (10-20 percent) with preeclampsia or eclampsia have HELLP syndrome. Preeclampsia is a condition that can happen after the 20th week of pregnancy or right after pregnancy. It’s when a pregnant woman has high blood pressure and signs that some of her organs, like her kidneys and liver, may not be working properly. Some of these signs include having protein in the urine, changes in vision and severe headache. Elcampsia is a condition that follows preeclampsia and causes seizures during pregnancy.

Most often HELLP develops during the third trimester of pregnancy (between 26 to 40 weeks gestation). Sometimes HELLP syndrome develops in the week after the baby is born.

Many women have high blood pressure and are diagnosed with preeclampsia before they develop HELLP syndrome. In some cases, HELLP symptoms are the first warning of preeclampsia.

HELLP syndrome is sometimes misdiagnosed as:

  • Flu or other viral illness
  • Gallbladder disease
  • Hepatitis
  • Idiopathic thrombocytopenic purpura (ITP)
  • Lupus flare
  • Thrombotic thrombocytopenic purpura

Some women who have HELLP syndrome get very sick. Rarely, HELLP syndrome can be fatal. Most women who have HELLP syndrome start to get better a couple of days after their babies are born.

The main treatment of HELLP syndrome is to deliver your baby as soon as possible, even if your baby is premature (before 37 weeks of pregnancy). Problems with the liver and other complications of HELLP syndrome can quickly get worse and be harmful to both the mother and child.

Your doctor may induce labor by giving you medicines to start labor, or may perform a C-section.

You may also receive:

  • A blood transfusion if bleeding problems become severe
  • Corticosteroid medicines to help the baby’s lungs develop faster
  • Medicines to treat high blood pressure
  • Magnesium sulfate infusion to prevent seizures

What is the chance for HELLP syndrome to recur?

Having a previous pregnancy affected by HELLP syndrome does increase the chance for it to recur in a subsequent pregnancy. However, estimates differ slightly depending on the source. For example, according to the Preeclampsia Foundation, the rate of recurrent HELLP syndrome ranges from 2% to 19%, depending upon the population studied 1. Others have estimated the risk to be up to 27% in subsequent pregnancies 2.

A 2015 meta-analysis of data from 512 women with HELLP syndrome who became pregnant again found that 7% of them (about 1 in 14) developed HELLP syndrome in a subsequent pregnancy. In addition, 18% of them developed preeclampsia, and 18% developed gestational hypertension 3.

Women who have had HELLP syndrome in a previous pregnancy should be monitored carefully throughout subsequent pregnancies in order to detect any signs of recurrence as early as possible 4.

What can I do to prevent recurrence of HELLP syndrome?

Currently there is no evidence that any therapy prevents HELLP syndrome from recurring, but data are limited 3.

Many different strategies to prevent preeclampsia (which can be associated with HELLP syndrome) have been studied; but, none have been found to be widely effective 5. Low-dose aspirin is the only drug for which there is some evidence of benefit in reducing the risk of preeclampsia 5. However, aspirin does not prevent progression to more severe disease and may exacerbate bleeding tendency in people with HELLP syndrome 5.

Early diagnosis and treatment allows for the best outcome for pregnancies affected by HELLP syndrome. Starting prenatal care early, and continuing prenatal care throughout pregnancy, can increase the chances that HELLP syndrome and other conditions are found and treated promptly 6. Women with a personal or family history of HELLP syndrome, preeclampsia, or other hypertensive disorders should inform their prenatal care providers, and should report any warning signs of these conditions immediately 7.

Is HELLP syndrome inherited?

A variety of genetic factors (both in the mother and fetus) have been found to play a role in the development of preeclampsia and HELLP syndrome 8. However, the condition is likely multifactorial. This means that several genetic and environmental factors likely interact to cause HELLP syndrome, and no one gene is thought to be responsible for the condition.

Some women may have a genetic predisposition to developing preeclampsia and related conditions, such as HELLP syndrome. This means that certain genetic factors increase a woman’s risk to develop HELLP syndrome. However, many women with a genetic predisposition will never develop HELLP syndrome.

If my mother had HELLP syndrome, am I at a high risk to develop it during my pregnancy?

While genetic factors are believed to be involved in the development of HELLP syndrome, their exact role is not fully understood. In addition, there are many other potential risk factors involved. Individuals interested in learning about their specific risks should discuss their family history and other concerns with an OB/GYN or a genetics professional.

How does family history contribute to the risk of preeclampsia, eclampsia and HELLP syndrome?

There are no specific genes known to cause an individual to have preeclampsia, eclampsia or HELLP syndrome. However, having a family history of one or more of these conditions may increase the risk for an individual to develop one or more of these conditions.

While there is limited information about familial recurrence of HELLP syndrome specifically, it is known that HELLP syndrome is more common in individuals who have preeclampsia or pregnancy induced hypertension 9. There is evidence that in studied populations severe preeclampsia (which is a risk factor for HELLP syndrome) is associated with having a family history of hypertension and/or hypercholesterolemia (high blood cholesterol and triglycerides), and that a family history of hypertensive disorders in general increases the risk of eclampsia and HELLP syndrome 10.

There have been a few examples of preeclampsia or eclampsia being present in 3- and 4-generations of families, and in one study (involving only an Icelandic population), the investigators suggested possible autosomal recessive or autosomal dominant inheritance among some of those families. Another study by Esplin et al. 11 in 2001 found that both men and women who were the product of a pregnancy complicated by preeclampsia were significantly more likely to have a child who was the product of a pregnancy complicated by preeclampsia. Authors of a 2004 study by Cnattingius et al. 12 concluded that genetic factors account for more than half of the risk of preeclampsia, and that maternal genes contribute more than fetal genes.

Individuals interested in learning about their personal risk to develop one or more of these conditions should speak with an OB/GYN or a genetics professional.

Are there any long term consequences involving the kidneys or liver in women who have had HELLP syndrome?

Long-term follow-up of women affected by HELLP syndrome is limited. A review of the current literature indicates that HELLP syndrome is not associated with long-term renal (kidney) complications 3. A similar review of the literature regarding liver function following HELLP syndrome indicates that in most cases, signs of liver damage resolve within a few days of delivery 13. In one long-term follow-up study of women with pregnancies affected by HELLP syndrome, there was a subset of women who experienced persistence of upper abdominal pain or fatigue following HELLP syndrome. The investigators set out to determine if these symptoms could be related to hepatic (liver) dysfunction. The results of this study showed that there was no biochemical evidence of impaired hepatocellular integrity, nor decreased synthesis of albumin (in other words, no evidence of long-term compromise to liver function). Some of the women studied did have elevated unconjugated bilirubin levels, a finding suggestive of Gilbert’s disease 13. More studies related to this association are needed.

Can the symptoms of HELLP syndrome be caused by a vitamin B12 deficiency?

A severe deficiency in folate and/or vitamin B12 vitamin can lead to features that are similar to those seen in HELLP syndrome. For this reason, these deficiencies should be considered as part of the differential diagnosis for HELLP syndrome 14.

HELLP syndrome effect on baby

The death rate among babies born to mothers with HELLP syndrome depends on the gestational age at delivery and birth weight and the development of the baby’s organs, especially the lungs (rather than the fact that HELLP syndrome was present, or the severity of signs and symptoms). Many babies are born prematurely (born before 37 weeks of pregnancy). This means that in many cases, the longer the pregnancy continues, the better the chance for survival and good health for the baby. Premature birth is common in mothers with HELLP syndrome 3. The rate of preterm delivery is 70%, with 15% occurring before 28 weeks of gestation 15. This is the leading cause of fetal or newborn death, with the overall risk of death ranging from 7 to 20 percent 15.

The mother’s laboratory abnormalities are not thought to be related to the chance of survival of a fetus or newborn. Additionally, HELLP syndrome does not affect liver function in the fetus or newborn 15. Unfortunately, there is very limited data available regarding the long-term follow-up of children born to mothers with HELLP syndrome.

HELLP syndrome vs Preeclampsia

Preeclampsia is a condition that affects some pregnant women, usually during the second half of pregnancy (from around 20 weeks) or soon after their baby is delivered.

Early signs of pre-eclampsia include having high blood pressure (hypertension) and protein in your urine (proteinuria).

Without immediate treatment, pre-eclampsia may lead to a number of serious complications, including:

  • convulsions (eclampsia)
  • HELLP syndrome (a combined liver and blood clotting disorder)
  • stroke

It’s unlikely that you’ll notice these signs, but they should be picked up during your routine antenatal appointments.

In some cases, further pre-eclampsia symptoms can develop, including:

  • swelling of the feet, ankles, face and hands caused by fluid retention (edema)
  • severe headache
  • vision problems
  • pain just below the ribs

If you notice any symptoms of pre-eclampsia, seek medical advice immediately by calling your doctor.

Although many cases are mild, pre-eclampsia can lead to serious complications for both mother and baby if it’s not monitored and treated.

The earlier pre-eclampsia is diagnosed and monitored, the better the outlook for mother and baby.

Mild preeclampsia affects up to 6% of pregnancies, and severe cases develop in about 1 to 2% of pregnancies.

There are a number of things that can increase your chances of developing preeclampsia, such as:

  • having diabetes, high blood pressure or kidney disease before starting pregnancy
  • having another condition, such as lupus or antiphospholipid syndrome
  • having developed the condition during a previous pregnancy

Other things that can slightly increase your chances of developing preeclampsia include:

  • having a family history of the condition
  • being over 40 years old
  • it having been at least 10 years since your last pregnancy
  • expecting multiple babies (twins or triplets)
  • having a body mass index (BMI) of 35 or over

If you have 2 or more of these together, your chances are higher.

If you’re thought to be at a high risk of developing pre-eclampsia, you may be advised to take a daily dose of low-dose aspirin from the 12th week of pregnancy until your baby is delivered.

Pre-eclampsia can only be cured by delivering the baby. If you have pre-eclampsia, you’ll be closely monitored until it’s possible to deliver the baby.

Once diagnosed, you’ll be referred to a hospital specialist for further assessment and any necessary treatment.

If you only have high blood pressure without any signs of pre-eclampsia, you can usually return home afterwards and attend regular (possibly daily) follow-up appointments.

If pre-eclampsia is confirmed, you’ll usually need to stay in hospital until your baby can be delivered.

Monitoring in hospital

While you’re in hospital, you and your baby will be monitored by:

  • having regular blood pressure checks to identify any abnormal increases
  • having regular urine samples taken to measure protein levels
  • having various blood tests – for example, to check your kidney and liver health
  • having ultrasound scans to check blood flow through the placenta, measure the growth of the baby, and observe the baby’s breathing and movements
  • electronically monitoring the baby’s heart rate using a process called cardiotocography, which can detect any stress or distress in the baby

Medication for high blood pressure

Medication is recommended to help lower your blood pressure. These medications reduce the likelihood of serious complications, such as stroke.

Some of the medications used regularly include labetalol, nifedipine or methyldopa.

Of these medications, only labetalol is specifically licensed for use in pregnant women with high blood pressure.

This means the medication has undergone clinical trials that have found it to be safe and effective for this purpose.

But while methyldopa and nifedipine aren’t licensed for use in pregnancy, they can be used “off-label” (outside their licence) if it’s felt the benefits of treatment are likely to outweigh the risks of harm to you or your baby.

These medications have been used by doctors for many years to treat pregnant women with high blood pressure.

They’re recommended as possible alternatives to labetalol in guidelines produced by the National Institute for Health and Care Excellence (NICE).

Your doctors may recommend one of them if they think it’s the most suitable medication for you.

If your doctors recommend treatment with one of these medications, you should be made aware that the medication is unlicensed in pregnancy and any risks should be explained before you agree to treatment, unless immediate treatment is needed in an emergency.

Other medications

Anticonvulsant medication may be prescribed to prevent fits if you have severe pre-eclampsia and your baby is due within 24 hours, or if you have had convulsions (fits).

They can also be used to treat fits if they occur.

Delivering your baby

In most cases of pre-eclampsia, having your baby at about the 37th to 38th week of pregnancy is recommended. This may mean that labor needs to be started artificially (known as induced labor) or you may need to have a caesarean section.

This is recommended because research suggests there’s no benefit in waiting for labor to start by itself after this point. Delivering the baby early can also reduce the risk of complications from pre-eclampsia.

If your condition becomes more severe before 37 weeks and there are serious concerns about the health of you or your baby, earlier delivery may be necessary.

Deliveries before 37 weeks are known as premature births and babies born before this point may not be fully developed.

You should be given information about the risks of both premature birth and pre-eclampsia so the best decision can be made about your treatment.

After the delivery

Although pre-eclampsia usually improves soon after your baby is born, complications can sometimes develop a few days later.

You may need to stay in hospital after the delivery so you can be monitored.

Your baby may also need to be monitored and stay in a hospital neonatal intensive care unit if they’re born prematurely.

These units have facilities that can replicate the functions of the womb and allow your baby to develop fully.

Once it’s safe to do so, you’ll be able to take your baby home.

You’ll usually need to have your blood pressure checked regularly after leaving hospital, and you may need to continue taking medication to lower your blood pressure for several weeks.

You should be offered a postnatal appointment 6 to 8 weeks after your baby is born to check your progress and decide if any treatment needs to continue. This appointment will usually be with your doctor.

HELLP syndrome cause

Experts don’t know what causes HELLP syndrome. Doctors also can’t predict who will get HELLP syndrome. Any pregnant woman may get HELLP syndrome. HELLP syndrome is considered to be a variant of preeclampsia. Sometimes the presence of HELLP syndrome is due to an underlying disease such as antiphospholipid syndrome. And if you’ve had HELLP syndrome before, you may have it again in 1 out of 4 future pregnancies (25 percent). HELLP syndrome is usually less severe the second time.

You’re more likely to get HELLP syndrome if you’re white and older than 25 years of age. You are at higher risk if you’ve had children before or if you had a problem with a past pregnancy.

You may be able to reduce your risk of having HELLP syndrome by getting prenatal care early and throughout your pregnancy. Getting regular prenatal care allows your provider to find and treat any problems like HELLP syndrome early.

A variety of genetic factors (both in the mother and fetus) have been found to play a role in the development of preeclampsia and HELLP syndrome 8. However, the condition is likely multifactorial. This means that several genetic and environmental factors likely interact to cause HELLP syndrome, and no one gene is thought to be responsible for the condition.

Some women may have a genetic predisposition to developing preeclampsia and related conditions, such as HELLP syndrome. This means that certain genetic factors increase a woman’s risk to develop HELLP syndrome. However, many women with a genetic predisposition will never develop HELLP syndrome.

Risk factors for HELLP syndrome

The following risk factors may increase a woman’s chance to develop HELLP syndrome 16:

  • Having a previous pregnancy with HELLP syndrome
  • Having preeclampsia or pregnancy induced hypertension
  • Being over age 25
  • Being Caucasian
  • Multiparous (given birth 2 or more times)

In less than 2 percent of women with HELLP syndrome, the underlying cause appears to be related to LCHAD deficiency in the fetus 17.

Can HELLP syndrome be prevented or avoided?

There is no known way to prevent HELLP syndrome. All pregnant women should start prenatal care early and continue it through the pregnancy. This allows your doctor to find and treat conditions such as HELLP syndrome right away. If you have HELLP syndrome during one pregnancy, you can have it again during your next pregnancy.

HELLP syndrome symptoms

Signs and symptoms can appear during pregnancy or after giving birth. Most women with HELLP syndrome have signs and symptoms before 37 weeks of pregnancy. But some women don’t have them until the week after they give birth.

HELLP syndrome signs and symptoms include:

  • Blurry vision
  • Fatigue (feeling really tired) or feeling unwell
  • Fluid retention, excess weight gain and swelling
  • Headache
  • Nausea or vomiting that continues to get worse
  • Nosebleed or other bleeding that doesn’t stop easily
  • Seizures or convulsions (rare)
  • Pain in the upper right or mid part of the abdomen

If you have any of these signs or symptoms, call the local emergency number or get to the hospital emergency room or labor and delivery unit immediately.

HELLP syndrome possible complications

There can be complications before and after the baby is delivered, including:

  • Disseminated intravascular coagulation (DIC). A clotting disorder that leads to excess bleeding (hemorrhage).
  • Fluid in the lungs (pulmonary edema)
  • Kidney failure
  • Liver hemorrhage and failure
  • Separation of the placenta from the uterine wall (placental abruption)

After the baby is born, HELLP syndrome goes away in most cases.

HELLP syndrome diagnosis

Your doctor will do a physical exam to check you for:

  • Belly pain or soreness, especially in the upper right side (your liver)
  • Enlarged liver
  • High blood pressure
  • Swelling in your legs

Your provider also may use a liver function test to check your liver enzyme levels or blood tests to check your platelet count. Excessive protein may be found in the urine. A CT scan can show bleeding into the liver. A CT scan is a test that uses X-rays and computers to take pictures of your body.

Tests of the baby’s health will be done. Tests include fetal non-stress test and ultrasound, among others.

Many women are diagnosed with preeclampsia before they have HELLP syndrome. Sometimes HELLP syndrome symptoms are the first sign of preeclampsia.

HELLP syndrome treatment

If you have HELLP syndrome, your doctor may give you medicine to control your blood pressure and prevent seizures. Sometimes women also need a blood transfusion. This is when you have new blood put into your body.

Women who have HELLP syndrome almost always need to give birth as soon as possible, even if the baby is born prematurely, before 37 weeks of pregnancy. Early birth is necessary because HELLP syndrome complications can get worse and harm both mom and baby.

If you aren’t too sick, your doctor may wait a few days before delivering your baby. Your doctor may give your corticosteroid medicines to help speed your baby’s lung growth before it is born. Your doctor also may induce your labor. This means he/she gives you medicines to make labor begin. Some women need a cesarean section (c-section). A c-section is surgery in which your baby is born through a cut that your doctor makes in your belly and uterus.

Without early treatment, 1 out of 4 women (25 percent) with HELLP syndrome has serious complications. Without any treatment, a small number of women die.

HELLP syndrome prognosis

Outcomes are most often good if HELLP syndrome is diagnosed early. It is very important to have regular prenatal checkups. You should also let your doctor know right away if you have symptoms of HELLP syndrome.

If you get diagnosed early, you will most likely be fine.

When HELLP syndrome is not treated early, up to 1 of 4 women develop serious complications. Without treatment, a small number of women die.

The death rate among babies born to mothers with HELLP syndrome depends on birth weight and the development of the baby’s organs, especially the lungs. Many babies are born prematurely (born before 37 weeks of pregnancy).

If you don’t get treatment early, you may develop complications that may occur before and after delivery. These include:

  • Clotting problems that can lead to hemorrhage (excessive bleeding). Disseminated intravsacular coagulation (DIC) – a clotting disorder that leads to excess bleeding (hemorrhage).
  • Fluid in your lungs (pulmonary edema).
  • Kidney failure.
  • Liver hemorrhage and failure.
  • Placental abruption (when the placenta separates from the wall of the uterus).

The risk of serious complications generally is higher for women with severe symptoms and for those with more severe laboratory abnormalities. Examples of complications include disseminated intravascular coagulation (DIC), placental abruption, acute kidney failure, and pulmonary edema. However, these complications are related. For example, placental abruption can cause disseminated intravascular coagulation (DIC), which then may cause acute kidney failure; acute kidney failure may lead to pulmonary edema. Of note, HELLP syndrome with or without kidney failure does not affect long-term kidney function. Other complications that have been reported include adult respiratory distress syndrome, sepsis, and stroke 3.

Once your baby is born, HELLP syndrome usually goes away within 2 days. If you have it once, you are more likely to have it again in future pregnancies. HELLP syndrome may return in up to 1 out of 4 future pregnancies.

References
  1. HELLP Syndrome. https://www.preeclampsia.org/health-information/hellp-syndrome
  2. HELLP Syndrome. https://emedicine.medscape.com/article/1394126-overview
  3. HELLP syndrome. https://www.uptodate.com/contents/hellp-syndrome
  4. HELLP Syndrome. https://action-on-pre-eclampsia.org.uk/public-area/pre-eclampsia-information/hellp/
  5. Phyllis August. Preeclampsia: Prevention. UpToDate. Waltham, MA: UpToDate; March, 2016
  6. HELLP syndrome. https://medlineplus.gov/ency/article/000890.htm
  7. HELLP syndrome. https://www.preeclampsia.org/health-information/hellp-syndrome
  8. Kjell Haram, Jan Helge Mortensen, and Bálint Nagy. Genetic Aspects of Preeclampsia and the HELLP Syndrome. Journal of Pregnancy. 2014
  9. HELLP Syndrome. http://americanpregnancy.org/pregnancy-complications/hellp-syndrome
  10. Family history of hypertension as an important risk factor for the development of severe preeclampsia. Acta Obstet Gynecol Scand. 2010 May;89(5):612-7. doi: 10.3109/00016341003623720. https://www.ncbi.nlm.nih.gov/pubmed/20423274
  11. Esplin, M. S., Fausett, M. B., Fraser, A., Kerber, R., Mineau, G., Carrillo, J., Varner, M. W. Paternal and maternal components of the predisposition to preeclampsia. New Eng. J. Med. 344: 867-872, 2001.
  12. Cnattingius, S., Reilly, M., Pawitan, Y., Lichtenstein, P. Maternal and fetal genetic factors account for most of familial aggregation of preeclampsia: a population-based Swedish cohort study. Am. J. Med. Genet. 130A: 365-371, 2004.
  13. Knapen MF, van Altena AM, Peters WH, Merkus HM, Jansen JB, Steegers EA. Liver function following pregnancy complicated by the HELLP syndrome. Br J Obstet Gynaecol. November 1998; 105(11):1208-10. https://www.ncbi.nlm.nih.gov/pubmed/?term=9853772
  14. Benali M, Bouassida M, Dhouib F, Bouzeidi K. Pseudo-HELLP syndrome par carence en folates et/ou en vitamine B12: à propos d’un cas[Pseudo-HELLP syndrome from folate and/or vitamin B12 deficiency: case report]. Pan Afr Med J. 2014;18:99. Published 2014 May 27. doi:10.11604/pamj.2014.18.99.2483 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232030/
  15. Cavaignac-Vitalis M, Vidal F, Simon-Toulza C, Boulot P, Guerby P, Chantalat E, Parant O. Conservative versus active management in HELLP syndrome: results from a cohort study. J Matern Fetal Neonatal Med. December, 2017; 21:1-7. https://www.ncbi.nlm.nih.gov/pubmed/29228827
  16. HELLP Syndrome. http://americanpregnancy.org/pregnancy-complications/hellp-syndrome/
  17. Sibai BM. HELLP syndrome. UpToDate. Waltham, MA: UpToDate; 2018
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