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Hepatic Rupture in Hemolysis, Elevated Liver Enzymes, Low Platelets Syndrome

Grand'Maison, Sophie, MD; Sauvé, Nadine, MD; Weber, Florence, MD; Dagenais, Michel, MD, PhD; Durand, Madeleine, MD, MSc; Mahone, Michèle, MD, MSc

doi: 10.1097/AOG.0b013e318245c283
Original Research
Free

OBJECTIVE: Rupture of hepatic hematoma associated with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome is a catastrophic complication of pregnancy. Maternal and fetal mortality rates are still high despite advances in diagnosis and treatment. We aimed to present our experience at two referral centers for hepatic disease and to compare it with cases from the literature.

METHODS: We reviewed nine cases that occurred over the past 6 years in our centers and made an extensive literature review covering the past 10 years. We reviewed and compared multiple outcomes for all these cases.

RESULTS: The median maternal age of our patients was 29 years (interquartile range 27–32). Embolization treatment was used with seven of nine (78%) of our patients compared with 5 of 88 (6%) in the literature (P<.001). Our maternal and fetal mortality rates were 0% (95% confidence interval [CI] 0–34%) and 30% (95% CI 7–65%), respectively, compared with 17% (95% CI 10–26%) and 38% (95% CI 31–52%]) from our review of the literature from 2000 to 2010.

CONCLUSION: The use of hepatic artery embolization to address hepatic rupture associated with HELLP syndrome may help minimize morbidity and maternal mortality.

LEVEL OF EVIDENCE: III

Hepatic artery embolization in stable patients may help to improve the maternal mortality rate of hepatic rupture attributable to hemolysis, elevated liver enzymes, low platelets syndrome.

From the Centre Hospitalier de l'Université de Montréal, Montreal, and the Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebéc, Canada.

Presented at the North American Society of Obstetric Medicine meeting, April 30, 2011, Boston, Massachusetts.

Corresponding author: Dr. Michèle Mahone, Hopital St-Luc du Centre Hospitalier de l'Université de Montréal, 1058 rue Saint-Denis, Montreal (Québec), Canada, H2X 3J4; e-mail: michele.mahone@umontreal.ca.

Financial Disclosure The authors did not report any potential conflicts of interest.

In 1844, Abercrombie1 was the first to describe hepatic rupture as the most catastrophic complication of pregnancy. This rare condition is seen primarily in association with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, which was first defined by Weinstein in 1982.2 HELLP syndrome is considered to be a variant of severe preeclampsia, although some authors believe it to be a separate entity.3 Serious maternal morbidity associated with HELLP syndrome includes disseminated intravascular coagulation, abruptio placentae, acute renal failure, pulmonary edema, retinal detachment, and subcapsular liver hematoma. The incidence of ruptured hepatic hematoma is between 1 in 45,000 and 1 in 225,000 pregnancies.46 It occurs in less than 2% of HELLP syndrome cases.7 Preeclampsia and HELLP syndrome are most often seen in young primigravid women, but multiparous and older preeclamptic women are at higher risk for hepatic rupture.8 Hepatic hematoma and rupture generally occur in the third or late second trimester, or in the immediate postpartum period.9 The diagnosis is not always easy to make; typically it is identified on ultrasonography or computed tomography when the patient is stable or sometimes when blood is seen directly by the obstetrician while performing a cesarean delivery.

There are two principal approaches to treatment: conservative, which includes hepatic artery embolization, and surgical, including packing, hemihepatectomy, liver transplantation, or a combination of these procedures. Based on a review of the literature from 1960 to 1997, the maternal and fetal mortality rates are 32% and 51%, respectively,10 remaining high despite advanced diagnosis and treatment.

The objective of this study is to present our experience as two referral centers for hepatic disease in treating hepatic rupture associated with HELLP syndrome, and to compare our maternal and fetal outcomes with cases from the literature within the past 10 years. We also aimed to review the treatment modalities to see if our therapeutic approach was similar to other reported cases.

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MATERIALS AND METHODS

Our hospital (the Centre Hospitalier de l'Université de Montréal) is a quaternary center for hepatic disease in the province of Quebec, and it is a secondary center for neonatology. We reviewed nine cases of hepatic rupture occurring in patients with HELLP syndrome who have been treated at the Centre Hospitalier de l'Université de Montréal and the Centre Hospitalier Universitaire de Sherbrooke between 2006 and 2010. HELLP syndrome was defined as a platelet count <100×109/L, aspartate aminotransferase 70 international units/L or more, and lactate dehydrogenase (LDH) 600 units/L or more. Hepatic rupture was defined as partial or complete fracture of the liver as seen during surgery or on imagery.

Cases were identified by retrospective search of hospital charts using the International Classification of Diseases, 9th Revision (indicating hypertension complicating pregnancy [642] and other disorders of liver [646.7]), from 1990 to 2010. All charts were reviewed to identify hepatic rupture during pregnancy. For all cases, charts were reviewed to collect information on maternal characteristics, clinical presentation, diagnostic studies, therapeutic modalities, and maternal and fetal outcomes.

To identify cases from the literature, we performed a literature search using PubMed between 2000 and 2010 to identify relevant articles. Our search was limited to articles in English and French, but we included articles in others languages when an English abstract was available. The search was conducted using the non-MeSH terms “hepatic rupture” and “HELLP syndrome.” We searched the reference lists of the primary articles and reviews for relevant articles not already captured in the literature search. This study was approved by our institutional review board (DSP directorate of professional services) of the Centre Hospitalier Université de Montréal, and the patients were asked to give informed consent.

Appropriate summary statistics were calculated to describe the characteristics of our patients and those from the literature (medians for nonnormally distributed continuous variables and proportions for binary or categorical variables). Exact confidence intervals were obtained for proportions, and differences between our case series and cases from the literature were compared using Fisher exact test for categorical variables and Wilcoxon rank-sum test for continuous variables. All statistical analysis was performed using STATA 11.

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RESULTS

We identified nine cases of hepatic rupture in HELLP patients. Table 1 presents their characteristics. The median maternal age was 29 years (range 23–35 years). Five of the women were primigravid and one woman had a twin pregnancy. Two women were not in the third trimester of their pregnancy. None of the women had personal or familial history of preeclampsia or HELLP, or personal history of high blood pressure or chronic kidney disease.

Table 1

Table 1

All women first consulted in another hospital in the surrounding area and were subsequently transferred to our centers. Eight women had preeclampsia or gestational hypertension. Six women eventually had cesarean deliveries, and three had vaginal deliveries.

As seen in Table 1, the principal presenting symptom was epigastric pain (six of nine). Five out of nine patients reported thoracic or right shoulder pain, and one of these women had symptoms just a few hours postpartum. Patient 4 had previously consulted for back pain and was sent home. She returned a few hours later in shock with thoracic and right shoulder pain. Diagnosis of hepatic rupture was made by abdominal ultrasonography in four women, abdominal computed tomography was performed in two women, and in two women cesarean delivery was followed by abdominal computed tomography (Fig. 1).

Fig. 1

Fig. 1

Table 1 also presents laboratory values of our patients. All women had the characteristics of HELLP syndrome. The mean aspartate aminotransferase level was 1,981 units/L, alanine aminotransferase was 1,766 units/L, LDH was 3,478.75 units/L, and mean platelet count was 53.89×109/L. Patient 2 had never had her LDH measured, but she had all of the other criteria for HELLP syndrome. The majority of the women had proteinuria.

Table 2 summarizes the principal treatments received by the patients as well as their clinical evolution. Six of them received antihypertensive therapy with varying medications: nifedipine, nitroprussiate, labetalol, metoprolol, and bisoprolol. All but one received magnesium sulfate for prevention of eclampsia. Two thirds (six of nine) of the patients received corticosteroid therapy. The median number of blood units and blood products (platelets, fresh-frozen plasma, or cryoglobulin) received by the patients were three (range 1–34) and 10 (range 0–46), respectively. Embolization treatment was used with seven of nine (78%) of our patients. Three women had hepatic artery embolization as sole treatment (two in the right artery and one in the left). One had surgery with packing only, and three had both surgical packing and then embolization. One woman required a right hepatectomy after embolization because of an infected hematoma. One woman did not have any intervention, although she was kept for clinical observation. We used recombinant factor VIIa in one case only (patient 4).

Table 2

Table 2

Plasma exchange was performed three times for patient 6 (our most severe case) because her platelet count was low and a hemolytic uremic syndrome was suspected, although it was later ruled out. She had necrosis of her right liver after embolization, with aspartate aminotransferase levels of 9,906 units/L. She also had a LDH level of 15,231 units/L, a nadir of platelets of 9×109/L, and an acute kidney failure that necessitated kidney replacement therapy. She also had many other complications and the longest length of stay at the hospital and in the intensive care unit (Table 2).

The median length of stay was 10 days (range 5–51), and each woman spent at least a few days in the intensive care unit. Two women did not have development of any complications of their disease after treatment or during their hospitalization. A majority of the others had at least pleural effusions. No maternal mortality occurred.

There was 30% fetal mortality (3 of 10, with one twin pregnancy). We had limited information about the newborns, because most of them were born in other hospitals and were not transferred with their mothers.

Five of these women were screened for thrombophilia during follow-up. Two were heterozygous for factor V Leiden mutation. Two women had subsequent pregnancies. One used acetylsalicylic acid and tinzaparin for prophylaxis of recurrence and had a successful pregnancy with no recurrence of HELLP syndrome. The other used acetylsalicylic acid and enoxaparin. She was induced at 38 weeks of gestation and had development of postpartum preeclampsia. Hepatic rupture did not reoccur.

We identified 93 cases of hepatic rupture in HELLP syndrome in the literature over the past 10 years (Table 3). Six were only available as abstracts. Results of the literature review are presented in Table 4. Of reviewed cases, 38 of 67 (57%) women were multiparous and 59 of 64 (92%) women had preeclampsia. Cesarean delivery was performed in 71 of 85 (84%) of the women. Median maternal age was 32 years (interquartile range 27–37 years). These characteristics were similar to those found in our nine cases. Different therapeutic modalities (detailed in Table 4) were used, which differed from those used in our centers. Compared with our patients, fewer patients were treated with embolization only (none compared with 33%, P=.001) or surgery and then embolization (six compared with 33%, P=.004), and more were treated with surgery only (58% compared with 11%, P=.001).

Table 3

Table 3

Table 4

Table 4

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DISCUSSION

In case reports and case series, hepatic rupture associated with HELLP syndrome is seen primarily in older multiparous women. Araujo et al11 in 2005 presented a case series of 10 women with hepatic rupture and the majority of them were older than age 35 years and multiparous, with a maximum of 15 pregnancies. In our centers, the majority of women were younger than age 30 years and mostly primigravid. The cases reported by Araujo occurred in Brazil, where the sociocultural environment is quite different from that of Canada, which might explain this difference.

The diagnosis of hepatic rupture is difficult to make because symptoms are common and nonspecific. After a detailed literature review, Rinehart et al10 documented the most frequent signs and symptoms of hepatic rupture and hemorrhage. Epigastric pain was the most frequent with 70%, followed by hypertension (66%), shock (56%), nausea and vomiting (25%), shoulder pain (21%), and headache (11%). These findings reflect what we have observed in our cases: six of nine (67%) patients had epigastric pain as the presenting symptom and five of nine (56%) had shoulder pain. These symptoms can be related to a vast number of other diagnoses, and that is why physicians should be more aware of this pathology. Abdominal ultrasonography and abdominal computed tomography scan remain the methods of choice in confirming this diagnosis if the patient is stable. Clinicians should choose the method of diagnosis that they can access most rapidly.9,12

For hepatic blunt trauma, it is known that early embolization can decrease the need for liver-related operations.13 A recent review noted that 86.3% of hepatic injuries are now managed without operative intervention.14 In 1999, Rinehart10 found that survival rate of hepatic rupture in HELLP syndrome was better with embolization. Only 6% of cases from the literature published after 2000 used embolization as part of their treatment, and always in combination with surgery. Seven of our patients were treated with embolization, and no deaths occurred. Even though our centers are tertiary in hepatic disease, our strategy of treatment infrequently includes surgery. Four women who were transferred to us with packing had surgery to unpack the liver, but only one woman had another type of surgery (hemihepatectomy) in our hospital. It is important to remember that embolization can have some severe complications such as hepatic or biliary tract necrosis, but we think that the treatment of hepatic rupture should be reviewed and that embolization should be used as first-line treatment if the woman is stable.

In 1976, Bis et al15 found a maternal mortality rate of 59% and a fetal mortality of 62%. Rinehart et al10 in their extensive literature review from 1960 to 1997 noted 141 cases of hepatic hemorrhage. The maternal and fetal mortality rates were 32% and 51%, respectively. In our centers, no maternal mortality occurred, and the fetal mortality rate was 30%. In our literature review covering the past 10 years (93 cases of hepatic rupture), maternal mortality was 17% and fetal mortality was 38%. Although our mortality rate was different from what was seen in our literature review, we consider our patients to have been in a similarly severe medical condition as those reported. Patient 6 had a prolonged intensive care unit stay and had multiple complications, and patient 7 required a hemihepatectomy because of an infected hematoma. Because of our small sample size, we cannot ascertain that the difference in mortality observed between our cases and those in the literature is not attributable to chance. However, we hypothesize that our observed mortality differs from other reviewed cases because of our preference for hepatic artery embolization. Furthermore, as a reference center, we do see the most severe cases and not the mild cases that tend to have lower mortality rates.

Hepatic rupture associated with HELLP syndrome is a rare but catastrophic complication of pregnancy. Even if the diagnosis is difficult to make because the symptoms are nonspecific and common, clinicians should always have a suspicion of hepatic rupture because of HELLP syndrome when a pregnant woman presents with epigastric or shoulder pain with hypertension or shock. The maternal and fetal mortality rates remain high in some reviews, but we believe that an early diagnosis and the rapid use of hepatic artery embolization could help to improve these statistics.

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