HELLP Syndrome

What is HELLP Syndrome?

HELLP syndrome is a condition indicated by three specific issues: breakdown of red blood cells (hemolysis), high liver enzyme levels showing liver damage, and low platelets that are needed for clotting. It is typically seen in pregnant women or those who have just given birth. Some people think HELLP syndrome might be a severe type of preeclampsia, a pregnancy complication, but this notion is under debate. Not everyone with HELLP syndrome shows risks signs of preeclampsia such as high blood pressure or protein in the urine. In fact, about 15-20% of HELLP syndrome patients don’t display these signs. If a woman has had either preeclampsia or HELLP syndrome before, she could possibly get it again in future pregnancies.

The risk for getting HELLP syndrome may increase with age and with the number of times a woman has been pregnant. There may also be a genetic component involved, making some people more likely to develop the condition. Recent reports also suggest that pregnant women with a SARS-CoV-2 infection (the virus causing COVID-19) might be at a higher risk for developing both preeclampsia and HELLP syndrome.

What Causes HELLP Syndrome?

The exact cause of HELLP syndrome, a life-threatening pregnancy complication, remains unknown. However, it’s believed to be a disorder caused by excessive inflammation in the body, triggered by a series of reactions known as the complement cascade.

Some medical professionals believe HELLP syndrome and preeclampsia (another pregnancy complication) may have similar causes. Both are thought to stem from poor placental development, but in HELLP syndrome, the complement system, or immune system reactions, become excessively activated, causing inflammation especially in the liver.

In some cases, HELLP syndrome results from a disorder known as complement dysregulation. This is a condition linked to tiny blood clots in the blood vessels, also referred to as thrombotic microangiopathy, and can manifest as pregnancy-related hemolytic uremic syndrome (HUS), a serious condition characterized by destruction of red blood cells and kidney failure.

One additional theory points to fetal long-chain 3-hydroxy acyl CoA dehydrogenase deficiency (LCHAD) as a contributing factor to the cause of HELLP syndrome, though this hasn’t been definitively proven. LCHAD is a genetic disorder affecting how the body breaks down certain fats to produce energy. However, testing for these genetic variants isn’t necessary as it doesn’t play a role in managing the condition.

Risk Factors and Frequency for HELLP Syndrome

HELLP syndrome is a condition that occurs in about 0.5% to 0.9% of pregnant women. Roughly 70% of these cases happen during the third trimester, or the last three months, of pregnancy. The rest of the cases usually occur within 48 hours after the baby is delivered. It’s important to note that HELLP syndrome can be very serious. The death rate for women with this condition can be as high as 24%. Additionally, there can be a death rate of up to 37% for newborns when the mother has this condition.

Signs and Symptoms of HELLP Syndrome

HELLP syndrome typically affects women who have had multiple pregnancies and are over 35 years of age. It commonly occurs between the 28th to 37th weeks of pregnancy (third trimester) or within a week after delivery. Symptoms can vary but often include:

• Abdominal pain in the middle or upper right side
• Nausea
• Vomiting
• Fatigue
• Yellow skin (jaundice)
• Increased abdominal size
• Swollen legs
• Headaches
• Changes in vision

Some women may experience severe bleeding, placental abruption, sudden kidney problems, liver hematoma (blood-filled swelling), or retinal detachment. During a physical examination, the patient usually has high blood pressure (over 140/90 mmHg), and might have fluid accumulation in the abdomen (ascites) or swollen feet and ankles (pedal edema). Tenderness may be felt in the upper right quadrant or middle of the abdomen, and there may be jaundice or visual disturbances. Detailed physical examination should be conducted if any of the mentioned complications are suspected.

Testing for HELLP Syndrome

When a pregnant woman in her third trimester, or within 7 days after giving birth, shows signs of HELLP syndrome and has newly detected high blood pressure or protein in the urine, certain lab tests are required to confirm the diagnosis of HELLP syndrome. These include:

* A complete blood count, which is a measurement of the cells that make up your blood.
* A peripheral smear, which checks the appearance of your blood cells under a microscope.
* Liver function tests. These measure levels of substances like aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin to gauge how well your liver is working.
* Creatinine test, which measures kidney function.

If the liver function tests come back abnormal, additional tests are needed. These include haptoglobin, lactate dehydrogenase (LDH), and coagulation studies like fibrinogen, prothrombin (PT), and activated partial thromboplastin time (PTT).

Doctors typically use the Tennessee classification to diagnose HELLP syndrome. This requires that all three of the following criteria are met:

1) Evidence of hemolysis. This means your red blood cells are being destroyed too quickly. This can be shown through at least two of the following signs:

* A peripheral smear that shows unusual-looking red blood cells.
* A serum bilirubin level higher than 1.2 mg/dl.
* Low serum haptoglobin (less than 25mg/dl) or LDH greater than twice the upper normal limit.
* Severe anemia (low red blood cell count) with hemoglobin less than 8 to 10 g/dl, depending on the pregnancy stage, unrelated to blood loss.

2) Elevated liver enzymes. AST or ALT should be over two times the upper normal level.

3) Low platelets. Blood should contain less than 100,000 cells/microL.

Sometimes, the Mississippi classification is used alongside the Tennessee classification to further classify patients with HELLP syndrome. It’s based on the platelet count, LDH, and AST or ALT levels.

When a patient meets some, but not all of the criteria, they are considered to have partial HELLP syndrome, which could potentially progress to full HELLP syndrome. Therefore, these patients should be monitored carefully.

Interestingly, in HELLP syndrome, platelet activity increases, but there is no effect on clotting factors. Therefore, PT, PTT, and fibrinogen are usually normal. However, if PT and PTT are prolonged or fibrinogen levels are low, it may suggest that DIC (a condition affecting blood clotting) may also be present.

Treatment Options for HELLP Syndrome

When a patient becomes seriously ill, the primary focus of medical treatment is generally supportive. This might include help with breathing using a ventilator, ensuring the heart and blood pressure are stable, controlling pain, monitoring fluid levels within the body, and providing suitable nutrition. Seriously ill patients can decline rapidly; therefore, they’re best looked after in well-resourced hospitals, which offer high levels of care for both mother and baby. If this level of care is not available, it might be necessary to move them to a facility that can provide such support once they are stable.

One of the first things doctors will do in this situation is to stabilize the patient and ensure the baby is ok. This typically involves a type of test called a non-stress test, and an ultrasound check called a biophysical profile.

Several medical specialists might be involved in the treatment process, depending on the patient’s needs, including doctors who specialize in the care of patients in intensive care (intensivists), liver disorders (hepatologists), kidneys disorders (nephrologists), blood disorders (hematologists), surgeries (surgeons), women’s health (gynecologists), and newborn care (neonatologists).

If the patient’s blood pressure is extremely high, medication – such as labetalol, hydralazine, or nifedipine – can be given to lower it. And if the patient is experiencing severe pain in the upper-right side of the abdomen and there are signs their liver might not be working properly, doctors may order an ultrasound, CT scan or MRI to check for serious liver problems, like a liver rupture, severe liver failure or liver bleeding. In some cases, a liver transplant may be necessary. Less severe cases might be treated using a less invasive procedure to block blood vessels supplying the liver (hepatic artery embolization).

Patients with conditions like Disseminated Intravascular Coagulation (DIC), a condition that affects the blood’s ability to clot, pulmonary edema, a condition that leads to fluid build up in the lungs, acute respiratory failure, and acute kidney injury need mainly supportive treatment and the appropriate management according to standard clinical guidelines.

There may be circumstances where the patient needs a large number of blood transfusions. These include cases where the patient’s hemoglobin levels are less than 7gm/dl, there’s severe bruising, severe blood in the urine, or suspected separation of the placenta from the uterus wall (placental abruption). In situations where there is active bleeding and low platelet counts, doctors might give a transfusion of platelets. If the patient also has DIC, doctors might provide fresh frozen plasma and cryoprecipitate, both of which are blood products.

In cases where the patient has a syndrome called HELLP, which consists of break down of red blood cells, elevated liver enzymes and low platelet count, and a condition called Thrombotic Thrombocytopenic Purpura (TTP) – a disorder that causes blood clots to form in small blood vessels throughout the body – doctors might use a treatment called therapeutic plasma exchange. This procedure essentially replaces the plasma in the patient’s blood.

Patients should be quickly referred to an obstetrician/gynecologist, a doctor who specializes in women’s health and pregnancy, to consider delivery of the baby, as it is the most effective treatment. If the baby is less than 34 weeks old, a medication called betamethasone might be given to help the baby’s lungs develop more quickly. To prevent seizures in the mother and help protect the baby’s brain, doctors might start magnesium sulfate soon after the patient arrives at the hospital. However, a medication called dexamethasone, previously thought to improve the outcomes of patients with HELLP syndrome, was found not to be beneficial in improving the outcomes for mothers or babies in two large clinical trials.

What else can HELLP Syndrome be?

HELLP syndrome, a condition that can occur in pregnancy, can have symptoms that look like other health issues. It’s key to distinguish HELLP syndrome from other conditions, particularly the following:

• Pre-eclampsia with DIC: This typically arises in the 3rd trimester like HELLP syndrome. The condition involves clotting factors and leads to increased PT and PTT, a difference from HELLP syndrome. Both conditions involve high blood pressure and protein in urine.
• Acute fatty liver of pregnancy (AFL): Like HELLP syndrome, AFL presents in the third trimester, but here, the liver is mainly injured. Direct bilirubin and ammonia levels are elevated, in contrast to HELLP syndrome, where these markers are unaffected. Also, individuals with AFL often show low blood sugar levels, unlike those with HELLP.
• Thrombotic thrombocytopenic purpura (TTP): This mainly occurs in the first trimester, unlike HELLP syndrome. TTP is characterised by fever, mental status change, kidney injury or blood in urine, hemolytic anemia, and low platelet count. Clotting is not affected and blood pressure is usually normal. TTP is also distinguished by reduced ADAMTS-13 levels and elevated VWF multimers.
• Systemic Lupus erythematosus flare-up: This condition, often simply called lupus, may share some symptoms with HELLP syndrome, such as low platelet count, hemolytic anemia, high blood pressure, and proteinuria. However, liver function tests usually come back normal, and symptoms specific to lupus like skin rashes, chest pain, arthritis, and fluid around the heart should indicate its presence.
• Antiphospholipid syndrome (APS): In this syndrome, liver function tests are normal, but hemolysis (breakdown of red blood cells) and thrombocytopenia (low platelet count) may occur. They might also show symptoms identical to those of HELLP syndrome, such as high blood pressure and proteinuria. But APS is mainly recognized by recurrent clotting incidents in blood vessels and repeated spontaneous abortions before 10 weeks gestation or fetal loss.
• Fulminant Viral hepatitis: This is another condition that shows up in the differential list for HELLP, which can be identified with the right tests and medical history.

It is essential for health care providers to correctly identify these conditions as they form a specific approach to treatment and care.

What to expect with HELLP Syndrome

HELLP syndrome is a very serious health condition. It has a mortality rate for women that varies greatly, from 0% to 24%, and it can also lead to perinatal death (death around the time of childbirth) in up to 37% of cases. The main reasons for death among women with HELLP syndrome include complications like uncontrolled bleeding or clotting in the blood vessels (known as disseminated intravascular coagulation), separation of the placenta from the uterus (placental abruption), severe bleeding after childbirth (postpartum haemorrhage), or severe kidney failure.

Disseminated intravascular coagulation is seen in 15% to 62.5% of patients. Placental abruption occurs in 11% to 25% of women with HELLP syndrome. Postpartum haemorrhage is experienced by 12.5% to 40% of women, and acute kidney failure happens in 36% to 50% of patients. The condition also significantly affects the health of the unborn child, leading to complications like placental abruption, less oxygen for the baby in the womb (intrauterine hypoxia), difficulty breathing at birth (asphyxia), being born too early (prematurity), and having low birth weight.

Once a woman has had HELLP syndrome, there is a 19% to 27% risk of it recurring in future pregnancies. These recurrences typically happen later during the pregnancy and are usually less severe after two occurrences.

Possible Complications When Diagnosed with HELLP Syndrome

HELLP syndrome is an extremely dangerous condition that poses a serious risk to both the mother and the newborn baby. The potential risks for the mother include a range of complications such as:

• Eclampsia (a severe form of high blood pressure during pregnancy)
• Placental abruption (when the placenta separates from the womb wall before birth)
• The need for a Cesarean section
• DIC (a condition affecting the blood’s clotting ability)
• Increased likelihood of clot formation
• Liver rupture or formation of a blood clot
• Sudden, catastrophic liver failure
• Strokes
• Bleeding in the brain
• Swelling in the lungs and brain
• Unstable heart and blood pressure
• Acute kidney damage
• Severe infections or sepsis
• Retinal detachment (a condition that could lead to blindness)
• Severe bleeding around the time of childbirth
• Potential death

The baby also faces serious risks, which include:

• Death around the time of birth
• Slow growth inside the womb (also known as IUGR)
• Preterm birth
• Low platelets, white and red blood cells
• Respiratory distress syndrome (a breathing disorder that is more common in premature babies)

Preventing HELLP Syndrome

If you’ve been diagnosed with HELLP syndrome, it’s important to understand the progression of this condition. Knowing the potential risks for both you and your baby (both during and after pregnancy) are essential. It’s equally vital that your family is informed about these risks.

While HELLP syndrome can possibly reoccur in future pregnancies, the chances of this can be lowered by leading a healthy lifestyle. Try to prevent conditions like high blood pressure and diabetes, as they can contribute to HELLP syndrome. Regular physical activity is also suggested.

In later pregnancies, it’s advised to start prenatal care and routine medical tests early. This can help spot any potential problems earlier, helping to tackle them before they become serious.