Keywords
HELLP syndrome - pre-eclampsia - liver - infarction - preterm
Hepatic infarction is a known, yet exceedingly rare, complication of hemolysis, elevated
liver enzymes, and low platelets (HELLP) syndrome. It is often described in patients
with antiphospholipid syndrome (APLS). APLS is an autoimmune disorder that can cause
serious adverse obstetric outcomes in women. Complications include recurrent spontaneous
abortion, preterm delivery, pre-eclampsia, intrauterine growth restriction, HELLP
syndrome, and other abnormalities of placentation. Outside of pregnancy women with
APLS may experience spontaneous thromboembolic events including deep vein thrombosis
and pulmonary embolism. Diagnosis of APLS is typically performed at the time of the
inciting event—blood clot, pulmonary embolism, miscarriage, preterm delivery—and then
again 12 weeks later for confirmation. Specific autoantibodies tested include anticardiolipin
immunoglobulin G (IgG) and immunoglobulin M (IgM), lupus anticoagulant, and anti-β
2 glycoprotein IgG and IgM.
Women with previously diagnosed APLS are often started on anticoagulation when they
become pregnant, with a low-molecular-weight heparin and/or aspirin. However, many
women are unaware that they have a diagnosis of APLS until they experience an initial
thrombotic event or an adverse obstetric outcome, often early miscarriage. Even with
treatment, women with APLS can still develop serious obstetrical complications including
pre-eclampsia, eclampsia, and HELLP syndrome. These can be life threatening to both
mother and infant.
Even without the diagnosis of APLS, it is possible to develop HELLP syndrome with
no prior pathology. The catastrophic complications of HELLP syndrome still exist without
the underlying pathophysiology of APLS. Women with HELLP syndrome can quickly develop
disseminated intravascular coagulopathy (DIC) requiring transfusion of blood, platelets,
clotting factors, and even plasma exchange.[1] Although HELLP syndrome is a rare event in the general population, it is important
to understand because of the high risk of loss of maternal life. APLS has long been
believed to be only a thrombotic disease but may also have a microangiopathic component
which can explain its correlation with HELLP syndrome. HELLP syndrome is noted to
occur almost exclusively in the third trimester, and very rarely before 27 weeks'
gestation.[2]
Our case represents a patient at the earlier end of expected gestational ages to experience
HELLP syndrome, with no prior pregnancy or thrombotic event to suggest a maternal
risk of HELLP syndrome such as APLS. Patients perceived to be at low risk may suffer
the most from obstetrical emergencies as we are not expecting them to happen. In the
absence of prior testing, it is possible to experience a major obstetrical emergency
such as HELLP syndrome without any prior suggestion of pathology, as was the case
in our patient.
Case Report
The patient is a 22-year-old, gravida one, para zero at 28 weeks and 5 days of gestation
presented to an outside hospital for severe abdominal pain, nausea, and vomiting in
the early morning hours. On presentation she was found to have severe range blood
pressures with a maximum pressure of 218/110 mm Hg. She required multiple intravenous
(IV) doses of hydralazine and labetalol to bring down her blood pressure, and was
started on magnesium sulfate for seizure prophylaxis. She also was noted to have abnormal
laboratories including a spot protein–creatinine ratio of 6,703 and aspart aminotransferase
(AST) of 202 IU/L and alanine aminotransferase (ALT) of 180 IU/L. At this time, her
platelets were 195,000/µL. Due to concern for pre-eclampsia with severe features and
imminent preterm delivery, she received betamethasone for fetal lung maturity and
the decision was made to transfer to a tertiary-care center.
By the time she arrived at our center, her blood pressures were again severely elevated
and her liver enzymes had tripled. She was quickly treated with multiple doses of
IV labetalol and PO nifedipine, without effect. Along with this newly refractory severe
hypertension, the patient was also found to have a sharp increase in AST to 1,195
IU/L and ALT to 909 IU/L, as well as drop in platelets to 105,000/µL. Decision was
made for immediate cesarean delivery for HELLP syndrome.
Cesarean delivery was uncomplicated with estimated blood loss of 600 mL. Her blood
pressure stabilized after delivery. However, her transaminases continued to rise.
Within 6 hours of delivery, her AST rose to 1,620 IU/L and ALT to 1,636 IU/L. Overnight,
they continued to rise, with AST reaching 2,065 IU/L and ALT at 2,380 IU/L. Her international
normalized ratio also rose to 1.4 from an initial level of 1.1 on admission. Her platelets
also dropped to 36,000/µL overnight. She continued to have right upper quadrant pain
and right subscapular pain. Computed tomography (CT) scan of the abdomen and pelvis
was performed and revealed a 10 cm × 10 cm × 14 cm area of hyperattenuation on the
right hepatic lobe concerning for ischemia versus infarction ([Fig. 1]). Transplant surgery was consulted, as well as the intensive care unit. Per transplant
recommendations, the patient underwent right upper quadrant ultrasound with Doppler,
which was again consistent with right hepatic infarction or ischemia. The patient
was transferred to the Medical Intensive Care Unit (MICU). Liver function tests (LFTs)
continued to rise and her blood counts continued to drop. She was ultimately transfused
two units of packed red blood cells and two units of fresh-frozen plasma. Her model
for end-stage liver disease score was calculated at 20 and the patient underwent a
series of tests including antiphospholipid panel, inherited thrombophilias, and hepatitis
panel all of which were within accepted parameters. LFTs began to downtrend by postoperative
day (POD) 3 and continued to do so during her admission. On discharge, her AST had
normalized and ALT was still elevated at 397 IU/L on POD 8. The patient had close
outpatient follow-up with maternal–fetal medicine and hepatology. Laboratories were
trended and were found to have normalized at an outpatient clinic visit on POD 20.
She was seen by hepatology outpatient twice within a month from delivery with normal
LFTs, and planned to repeat LFTs in 3 months. Their notes state that they expect some
areas of infarction to regenerate and others to be replaced by fibrous tissue, with
some potential for long-term consequences of ischemic cholangiopathy and chronic liver
disease. They continue to recommend regular follow-up. Patient planned to have repeat
APLS laboratories at 12 weeks after first set but was lost to follow-up.
Fig. 1 Computed tomography of the abdomen and pelvis showing 60% infarction of right hepatic
lobe.
Discussion
HELLP syndrome is a potential complication of pregnancies, often associated with severe
pre-eclampsia. HELLP syndrome has been estimated to complicate 0.5 to 0.9% of all
pregnancies, and 10 to 20% of all cases of pre-eclampsia with severe features.[3] The diagnosis of pre-eclampsia with severe features involves extreme elevations
in blood pressure combined with evidence of end-organ damage. Approximately 10% of
pregnant women with severe pre-eclampsia will develop abnormal LFTs. HELLP syndrome
occurs within 48 hours of delivery, 20% of the time.[4]
[12] A majority of these cases resolve spontaneously, without lasting damage to the liver.
A concerning symptom that some women may experience in the setting of pre-eclampsia
with impending liver damage is epigastric pain, or more specifically, right upper
quadrant pain.[3] A major cause of concern when this symptom is detected is that a hematoma may be
developing within the liver capsule. Potentially, the most catastrophic outcome of
this would be hepatic rupture, which can lead to maternal death.[1] Several case reports have described women with HELLP syndrome who ultimately suffered
hepatic infarction, evidenced on imaging studies. When hepatic damage is extensive
enough, some of these women have undergone hepatic transplantation. From October 1987
to December 2006, there have been eight liver transplants in the United States performed
for the indication of HELLP syndrome, often with the complication of liver necrosis
and liver failure following hepatic rupture. Worldwide, there are also case reports
of hepatic transplant as the ultimate treatment for HELLP syndrome's most devastating
complications.
The mainstay of supportive management includes transfusion of blood products as needed,
correction of coagulopathy often seen with HELLP syndrome, and serial imaging and
LFT assays.[2] Platelets and blood are repleted as needed based on the complete blood count. Many
advocate for the use of corticosteroids as well. Historically, it was thought that
the mainstay of treatment for HELLP syndrome should be immediate delivery. There is
now evidence that stabilizing these patients first with antepartum corticosteroids
can improve outcomes and reduce maternal and fetal morbidities and mortalities.[5] Not all studies agree on this point, however. It is clear that corticosteroids can
improve laboratory values such as platelet counts and liver enzymes, but this does
not always equate improved maternal outcomes. A systematic review of the literature
from 2015 sets out to investigate the overall impact of corticosteroids on women with
HELLP syndrome, and ultimately found that it improves platelet count and serum lactate
dehydrogenase. These clinical outcomes reduced hospital stay and ICU admissions, but
did not necessarily correlate to maternal survival or decreased morbidity.[6] Corticosteroids are still used by many physicians in the treatment of HELLP syndrome,
especially when plasmapheresis is being performed.
Many recognize the utility of plasma exchange in the treatment of HELLP syndrome,
noting its significant reduction in maternal mortality. A study from Turkey in 2005
treated 29 patients with HELLP syndrome and compared them with 26 patients in the
control group. Maternal mortality was 23.1% in the control group, with no deaths in
the treatment arm. The patients treated with plasma exchange also experienced more
rapid improvement of their laboratory abnormalities including platelet count, AST,
ALT, and lactate.[7] Plasmapheresis is sometimes reserved only for patients with HELLP syndrome refractory
to other supportive treatments, or those who have developed DIC. In women who have
been treated with platelet transfusions without improvement of their disease, plasmapheresis
is often indicated. One case report discusses the use of plasma exchange therapy in
the treatment of hepatic infarction in the setting of HELLP syndrome, as well as serial
imaging studies.[8] Corticosteroids are often used during plasma exchange to prevent the development
of new autoantibodies, which are actively being filtered out by the plasma exchange
procedure.
Aside from laboratory abnormalities and DIC, another catastrophic complication of
HELLP syndrome is subcapsular liver hematoma. Hematomas of this nature can rupture,
which is a rare but fatal occurrence. In addition to avoiding direct manipulation
with the liver, either during physical examinations or during cesarean section, special
care must be taken with abdominal imaging when there is concern for hepatic injury.
Although studies have shown that imaging abnormalities are rarely present in HELLP
syndrome, when they are present, they can help dictate clinical decision making.[9] Preferred imaging studies include ultrasound, CT, magnetic resonance imaging, or
angiography. Abdominal CT is believed to be more sensitive than ultrasound for recognizing
hematomas and the true extent of any hepatic hemorrhage.[10] Serial imaging can help detect a growing hepatic hematoma, and can track any worsening
necrosis of the liver. Additionally, imaging can detect abnormalities in the liver
that may not be evident in laboratory testing. It is recommended to obtain imaging
of the liver if HELLP syndrome is suspected, regardless of the liver enzyme tests.
Specifically, patients with right upper quadrant pain, neck pain, shoulder pain, or
relapsing hypotension should undergo imaging.[11] In the case of our patient, serial CT imaging was used to monitor the infarcted
left lobe of the liver while the patient was being worked up by the transplant team
for potential surgery.
Our case presents a young patient with no prior medical comorbidities in a low-risk
pregnancy who developed a hepatic infarction in the setting of HELLP syndrome. The
patient fortunately recovered her liver function and is expected to regenerate much
of her hepatic tissue; however, we cannot yet know if she endured lasting hepatic
injury or diminished function throughout her life. Further research into this area
is needed to determine the long-term outcomes of women with liver injury related to
pregnancy complications to better assist in patient counseling and education.
