Introduction

Liver disorders complicate up to 3% of all pregnancies and the spectrum of disease varies from mild to gross derangements. HELLP syndrome is a life threatening complication of pre-eclampsia with a mortality rate of 1%. It is characterized by hemolysis, elevated liver enzymes and low platelet counts. Other manifestations of HELLP syndrome include: disseminated intravascular coagulation (DIC) in 21%, acute renal failure in 7.7%,pulmonary edema in 6% and subcapsular liver hematoma in 0.9% of cases. [1]. Spontaneous hepatic rupture was first described by Abercrombie in 1844, it is a rare event with an incidence of 1:45,000 to 1:225,000 deliveries. The incidence of spontaneous hepatic rupture with self-contained hematomas is unknown [2]. This large variation in incidence could reflect under-reporting of the condition and failure to recognize the milder cases with self-contained hematomas. The maternal mortality is as high as 60% with a fetal mortality of 56 to 75% [2]. A systematic literature review published by Haram et.al. found that hepatic rupture had an incidence of 1% to <2% in patients with HELLP syndrome[3]. We present a pregnant patient with severe HELLP and hepatic rupture .

Case

A 23 year-old woman with medical history of intermittent asthma and ectopic pregnancy was admitted with headache, abdominal pain and vomiting of two days duration. She was at 33 weeks gestational age; gravida 3, para 0, abortions 2;antenatal care was done at Dominican Republic and was reported to be uneventful. She did not take medications and she denied any toxic habits.

Her examination at the time of presentation was remarkable for elevated blood pressure (150/95 mmHg), mild lower abdominal tenderness and trace pedal edema. Fetal exam revealed a 32 week 3 day-old fetus in cephalic position with anterior placenta, bio- physical profile of 8/8, amniotic fluid index (AFI) of 7 cm and estimated fetal weight of 1919g. Urine dipstick was strongly positive for proteins. She was admitted to the labor and delivery unit with a diagnosis of pre-eclampsia, started on magnesium, steroids and labetalol. Laboratory (labs) results on admission are shown in table 1. During the next two days she continued to have intermittent abdominal pain and headaches. A cesarean section was performed 68 hours after admission. In the recovery room, the patient was noted to be hypotensive, tachycardic and anuric. Repeat labs (Table 1) revealed new onset thrombocytopenia and worsening liver function. She had worsening right upper quadrant pain and on examination the surgical site was clean with a tender right upper quadrant. Bedside ultrasound showed post operative changes without any hepatic abnormality or hemorrhage. Patient’s condition continued to deteriorate and she required intubation and mechanical ventilation.

In the intensive care unit, she was in shock requiring vasopressors. She had abnormal coagulation parameters suggestive of disseminated intravascular coagulation. She was out of shock in the next 24 hours. She remained anemic despite transfusions. A repeated abdominal ultrasound showed a ruptured hepatic hematoma with intra-peritoneal free fluid and peri-hepatic blood collection. An abdominal computed tomogram (CT) angiogram (Figure 1) confirmed the ultrasound findings and did not reveal acute bleeding. Over the next few days she received multiple blood product transfusions including packed red cells (15 units), fresh frozen plasma (13 units), platelets (36 units) and Factor 7.The patient was managed conservatively and subsequently she developed acute anuric renal failure. She was deemed a poor surgical candidate despite elevated intra-abdominal pressures and dialysis was initiated. Hospital acquired pneumonia and urinary tract infection with resistant Klebsiella developed followed by septic shock. She died on the 15th day of admission.

Figure 1

Axial and coronal reconstructions demonstrating hepatic hematoma and intra-abdominal free fluid

Table 1

Laboratory profile during hospital course

Discussion

Spontaneous hepatic rupture is an uncommon complication of HELLP syndrome. The pathogenesis for the rupture is unclear. It occurs usually in the setting of severe pre-eclampsia and HELLP syndrome, which is characterized by severe vasospasm and fibrin deposition [4]. Physical trauma, such as placement of tight abdominal binders or deep abdominal palpation have been suggested as precipitating factors for the development of the liver hematoma. [2]. Rademaker described a sequence of events including infarction, neovascularization, hematoma and a minor trauma precipitating the rupture [5]. Irrespective of the mechanism, it has been observed that the liver shows areas of necrosis with multiple lacerations. Most hematomas appears to involve the right lobe, mostly in the anterior and superior areas. Microscopically, periportal necrosis and fibrin deposition in capillaries indicate that disseminated intravascular coagulation (DIC) could play an important role in the pathogenesis [6]. In our patient, there was no report of any abdominal trauma.

The clinical presentation is usually non specific. Epigastric or right upper quadrant abdominal pain, nausea, vomiting and headaches are the most common symptoms [2, 4, 5, 6, 7]. Several risk factors have been identified based on demographics and include multiparity and maternal age in the late twenties. The condition usually presents in the third trimester in the setting of HELLP or severe pre-eclampsia. The actual event of hepatic rupture is heralded by hemorrhagic or hypovolemic shock. In the absence of shock, the diagnosis is usually missed [2]. The differential diagnosis for a patient presenting with abdominal pain and abnormal liver enzymes is wide, including HELLP, disseminated intravascular coagulation (DIC), hemolytic-uremic syndrome (HUS), severe sepsis, acute fatty liver of pregnancy, lupus and any other acute abdominal pathology such as appendicitis or cholecystitis[8]. The diagnosis is reached through specific laboratory tests and imaging studies. Blood tests usually reveal features of HELLP syndrome, including anemia, hemolysis, elevated liver enzymes and low platelet counts [9]. In addition, elevated lactate dehydrogenase (LDH) levels may be noticed prior to hepatic rupture [4]. Diagnostic Imaging studies include abdominal ultrasound,CT with contrast, magnetic resonance imaging (MRI) and digital subtraction angiography. On ultrasound, acute subcapsular hematoma appears as a crescent shaped collection of echogenic fluid just below the liver capsule, and over time may appear cystic and hypoechoic. This testing modality is especially useful when the patient is unstable for transfer for CT study.CT imaging is considered more sensitive than ultrasound,with the fluidcollection initially appearing hyperdense, changing progressively to a hypodense collection over time [10].Magnetic resonance imaging may be more useful in the setting of chronic hematomas. There is also decreased risk of radiation to the fetus with MRI [6]. Our patient underwent a post-operatively bedside ultrasound which did not reveal the subcapsular hematoma. However a subsequent ultrasound revealed the hematoma and intraperitoneal blood.

The management of patients with hepatic rupture is challenging and may be surgical or non surgical depending on whether the patient is actively bleeding. Successful non-surgical management with close hemodynamic monitoring and transfusion support has been describedin patients without active bleeding and in high surgical risk patients [11, 12].

Despite surgery, hemorrhagic shock remains the cause of death in over one third of the patients.Definitivereported surgical procedures include ligation, lobectomy or hepatectomy or liver transplantation in selected cases [7]. Surgery needs to be accompanied by intensive care with blood product support. Angio-embolization has been described as an adjunct to surgery, or in cases where patients have failed surgery or are poor surgical candidates [2].In our patient, surgery or embolization was not considered due to lack of active bleeding inCT angiogram. Later, when she developedintra-abdominal hypertensionand acute renal failure, she was deemed apoor surgical candidate with very high intra-operative mortality risk.

Liver transplantation also plays an important role in management. The indications for transplant include liver necrosis, uncontrolled bleeding and liver failure [13]. The use of liver transplant has increased over past decade with improved survival [14]. Auxiliary transplant and hepatectomy with orthoptic transplant have both been described in HELLP and liver rupture with good results [15]. Shames et.al describe an algorithm for liver rupture culminating in hepatectomy, temporary portocaval shuntwith eventual liver transplantation in case of continued bleeding. In addition, they recommend those patient to be managedin a specialized liver transplant center [16]. The risk of pre-eclampsia in subsequent pregnancies is around 20%, while the rates of recurrent HELLP ranges from 2 to 19%. There are no preventive measures for recurrent HELLP. Mothers should be made aware of the risks prior to pregnancy and the pregnancy should be closely monitored [9].

Conclusion

Our case highlights the fatal nature of hepatic rupture and its relatively "benign" presentation. Due to its rarity, it is not encountered by most intensivist or obstetric professionals. A high index of suspicion is necessary to diagnose hepatic rupture in its early stages. Diagnosis and management is a multidisciplinary effort involving the intensivist, obstetrician, surgeon and radiologist. Early surgical intervention with aggressive blood product support appears to be the current standard, though the best course of management is yet to be defined.