Rapidly progressing HELLP syndrome and massive liver destruction in a 22-year-old female pregnant with monochorionic diamniotic gemelli

Abstract

Haemolysis Elevated Liver parameters and Low Platelets (HELLP) syndrome can present with abdominal pain as the only symptom. It can be rapid with failure of multiple organs and is a cause of maternal death. A 22-year-old female pregnant with twins contacted her local hospital due to abdominal pain. Within 20 hours of the debut of the abdominal pain, a caesarean section was performed, the patient was re-operated due to the suspicion of abdominal bleeding. Bescause she was hypotensive and blood tests showed signs of liver destruction and acidosis, she was transferred to the intensive care unit (ICU). During an admission of 40 days, the patient received 5 plasmapheresis treatments and 10 courses of haemodialysis. CT scans showed massive liver haematomas intraparenchymal and subcapsular. The CT scan images are very interesting and included in the case report.

This case presents a good prognosis after a rapid progression of HELLP in spite of a dramatic clinical presentation. This topic is of great interest to a wide spectre of clinicians, as an early multidisciplinary approach is necessary.

Background

We wish to present a case of Haemolysis Elevated Liver parameters and Low Platelets (HELLP) syndrome with a rapid course and severe liver haematomas as illustrated by CT images. The prognosis of HELLP syndrome is dependent on an early and multidisciplinary effort. In this case report, the multidisciplinary teamwork is reflected in the four different specialties of the authors.

The syndrome of HELLP is a cause of maternal mortality.¹

The syndrome of HELLP was first described in 1982 by Weinstein.¹ HELLP is a rare diagnosis as it occurs in 0.2%–0.8% of all pregnancies.²

A prospective study in 1993 of 442 pregnancies complicated with HELLP found a maternal mortality of 1.1%. Subcapsular liver haematomas were found in 0.9% of the 442 pregnancies complicated by HELLP.¹ Sixty-five per cent of the patients presented with symptoms of right-upper quadrant or epigastric pain. It is described that women who survive massive destruction of the liver, during the course of HELLP, will recover without permanent liver damage.³

In 2017, approximately 810 women died everyday due to disorders related to pregnancy and childbirth. WHO published a report in 2014 regarding causes of maternal mortality worldwide. Direct obstetric causes of maternal deaths accounted for 73% of all maternal deaths worldwide between 2003 and 2009. Hypertension and hypertension-related disorders, including the ICD 14.20 for HELLP syndrome, were the second most common direct obstetric causes worldwide of maternal mortality.⁴

We report a case of rapidly progressing HELLP syndrome with massive liver destruction in a 22-year-old female pregnant with monochorionic diamniotic gemelli. The patient recovered clinically completely alone on primary supportive and medical treatment.

Case presentation

Our patient was at gestational age (GA) 24+3, in a gemelli pregnancy, she was routinely scanned and the suspicion of intrauterine growth restriction (IUGR) was raised which meant that the observation of the patient was intensified. The patient had no history of hypertension or symptoms of pre-eclampsia (PE) in a previous pregnancy.

The patient contacted her local hospital at GA 27+3 due to abdominal pain in the upper right quadrant during the night. The suspicion of HELLP was raised due to severe abdominal pain and hypertension (153/98 mm Hg). There was no headache, oedema, visual disturbances nor proteinuria. Thrombocyte count was normal, but liver enzymes were elevated with alanine-aminotransferase (ALAT) 430 U/L and lactate-dehydrogenase (LDH) 808 U/L. She was treated with celestone, labetalol and atosiban at the primary hospital. Magnesium sulfate (MgSO4) infusion, as a prophylaxis of seizures, was initiated and approximately 3 hours after the first contact the patient was referred to a tertiary hospital.

Caesarean section (CS) was performed due to decreasing thrombocytes (table 1) and increasing pain of the abdomen, thus within 20 hours of the debut of the abdominal pain. There were no direct fetal indications for the delivery. The patient had two living boys with estimated fetal weights of 638 g and 609 g combined with reduced umbilical flow corresponding to severe IUGR of −36% and −39%.

Table 1.

Laboratory values of interest (where available)

	Day of CS	2 days after CS	After 1 week	After 2 weeks	After 1 month
Haptoglobin, g/L	0.48		0.10	0.10	1.65
Bilirubin, umol/L	34	37	37	28	9
Trombocytes, x109/L	96	56	92	274	372
Alanine-aminotransferase (ALAT), U/L	1060		208	33	26
Aspartate-amintranferase (ASAT), U/L	1840		331		76
Lactate-dehydrogenase (LDH), U/L	1900		1250	756	321
Creatinine, μmol/L	47		71	426	55

CS, caesarean section.

During the CS, the patient turned hypotensive, anaemic (haemoglobin 7.9 g/dL) and metabolically acidotic with a pH of 7.14. The abdomen was increasingly expanding. Acute ultrasound showed signs of an accumulation under the right diaphragm and the patient was reoperated due to suspicion of bleeding. No intra-abdominal bleeding was found. From the stomach, 250 mL of blood was evacuated with a gastrointestinal tube, the origin of this was not clear. An immediate effect on the acidosis was seen after blood transfusions, but the patient had an increasing lactate acidosis (lactate 12 mmol/L). Meanwhile expert ultrasound found the accumulation suspicious of liver haematoma, which lead to a CT abdomen with contrast, that revealed widespread intraparenchymal haematomas in the liver.

The patient was transferred to the intensive care unit (ICU) still sedated and ventilated, and continuously hypotensive despite pressor therapy. Steroid treatment was initiated.

Three hours after the CS, the patient showed continuous signs of liver damage and haemolysis.

The following day plasma exchange therapy was initiated due to the lack of improvement despite delivery and steroid treatment. She received daily treatments of plasma exchange therapy with 3 L fresh frozen plasma for 5 days. She also received haemodialysis due to acute kidney injury (AKI). She received a standard treatment of dialysis for 3 weeks at the end of which her creatinine values stabilised interdialytically and she regained diuresis. The kidney function was normal, as evaluated by creatinine, after approximately 6 weeks.

Three weeks after the CS, the CT of the abdomen was repeated:

Contrast-enhanced CT abdomen revealed changes consistent with severe HELLP syndrome. In the liver widespread intraparenchymal haematomas were found as well as a bigger subcapsular haematoma in both of the liver lobes (figure 1).

Figure 1.

CT abdomen after caesarean section.

Due to the large haematomas in the liver and a suspicion of infection in these areas, the patient had an intrahepatic drain for 4 days with a production of 40–550 mL of bloody fluid per day. There was no microbiological growth in the fluid.

After 15 days in the ICU, the patient was transferred to the nephrology department. She recovered clinically and 2 months after admission, she was referred to her local hospital.

Outcome and follow-up

The ongoing outpatient controls of the patient show almost complete recovery of the liver haematomas. Liver biopsy was never performed

A contrast-enhanced CT scan of the abdomen after 5 months revealed that there were still big areas with haemorrhage sequelae in the liver. Especially in the right liver lobe intrahepatically and in the upper lateral part. The areas were still low attenuated, but now more well defined. The liver had almost returned to normal shape and size, and the diaphragm had returned to normal position. There was no longer haemoperitoneum (figure 2).

Figure 2.

CT abdomen 5 months after admission.

Discussion

The diagnosis of HELLP syndrome is diagnosed by the presence of haemolysis based on peripheral blood smear, elevated indirect bilirubin levels or low serum haptoglobin levels in association with significant elevation of liver enzymes and platelet count below 100×10⁹/L in pregnancy.⁵

The pathophysiology of HELLP is still under investigation. A large review by Powe et al, on the evidence of the pathophysiology of PE, suggests that the maternal disease is attributable to antiangiogenic factors released by an abnormal placenta.⁶

These antiangiogenic factors antagonise the effects of proangiogenic factors vascular endothelial growth factor (VEGF), placenta derived growth factor (PlGF) and transforming growth factor-β (TGF-β), which are important in the maintenance of the vascular endothelium. In PE, excess placental secretion of soluble fms-like tyrosinekinase 1 (sFlt1) and soluble endoglin (sEng) (two endogenous circulating antiangiogenic proteins) inhibits VEGF and TGF-β1 signalling, respectively, in the vasculature. This results in endothelial cell dysfunction, including decreased prostacyclin, nitric oxide production and release of procoagulant proteins. These factors trigger the vascular endothelium resulting in an inflammatory response leading to angiopathy. This was, among others, showed by the group of Powe et al. They showed the effect of the antiangiogenic proteins in pregnant rats.⁶ The results of the angiopathy are haemolysis and reduced portal flow in the liver. The pathophysiology of HELLP is due to abnormal placentation in the first trimester. The maternal signs occur in the second half of the pregnancy and are thought to represent the response to emitted soluble factors from a stressed, hypoxic and dysfunctional placenta.²

The clinical presentation varies with more than 50% of patients presenting with nothing else than abdominal pain.³ This makes it a differential diagnostic challenge.

A classification of HELLP syndrome was described by Martin et al on the basis of the lowest level of platelets; class 1 platelets <50 ×10⁹/L, class 2 between 50 and 100 ×10⁹/L and class 3 between 100 and 150 ×10⁹/L. According to this classification, the patient of this case report had class 2 HELLP. Class 1 patients have a higher maternal morbidity and are more frequently treated with plasma exchange therapy.¹

Subcapsular liver haematoma may present with non-specific symptoms and signs—none of which are diagnostic. There is no consensus on the management of subcapsular liver haematoma. Unruptured haematomas can be conservatively managed. The literature is scant and retrospective. Data on follow-up are limited.⁷ In our case, the patient was treated with a liver drainage. No biopsy or surgical treatment was initiated. Our patient was never anhepatic, but in such rare cases, liver transplantation can become necessary.³

The use of plasma exchange therapy in HELLP syndrome remains very controversial and the evidence is scant. Plasma exchange therapy is reported to be used in a retrospective study of women with HELLP. It suggests the use of plasma exchange therapy in the treatment of HELLP in patients that failed to reverse after delivery and/or were unresponsive to glucocorticoids.⁸ The effect seen by plasma exchange may in fact just be the effect of time/delivery and is not considered to be part of the standard treatment for HELLP.

As the patient had liver failure and haemolysis, one might suspect that the solely effect of adding coagulation factors, via plasma, could be the reason for an effect of plasma exchange.

Our patient developed haemodialysis-dependent AKI. We believe that this was caused by acute tubular necrosis, as this is the predominant lesion seen in postpartum kidney biopsies. If severe, PE alone is sufficient to induce acute tubular necrosis.⁹

As there is no consensus of the treatment of these patients, it is important that gynaecologists, surgeons, nephrologists and intensive care doctors can work closely together in an intensive care setting, when treating these patients with multiorgan failure.

Similar case reports describe and enlighten the very fast and serious deterioration of patients diagnosed with HELLP syndrome.

Guo et al described a patient diagnosed with HELLP and a CT scan revealing hepatic infarction. The patient was treated with haemodialysis, plasma exchange therapy, supportive treatment and drainage of ascites and pleural fluid. She was asymptomatic and without complications at 6 months follow-up.¹⁰

Ryan et al described a patient diagnosed with HELLP syndrome and liver infarction on MRI. After 50 days, an MRI showed almost complete resolution of the liver infarction.¹¹

Karateke et al described a patient with HELLP and subcapsular liver haematoma treated with supportive therapy in the ICU. After 8 weeks post partum, there were no signs of liver haematoma on an ultrasound.¹²

Szeremeta et al described a patient with spontaneous hepatic rupture and intraperitoneal haemorrhage due to HELLP syndrome. It describes the seriousness of the syndrome with death of the fetus.¹³

Only in the case of Szeremeta invasive treatment, with suture and packaging of the liver, was described. The mother survived and was operated after CS of a stillborn.

Although the prognosis of the syndrome is good, even if complicated by liver haematoma, the treatment in the acute setting is to be taken very seriously. Our case, as well as the above mentioned, highlights the importance of teamwork between colleagues from various specialties in an early effort, because HELLP is a syndrome with the risk of multiorgan failure and maternal mortality.

Learning points.

• The primary treatment of haemolysis elevated liver parameters and low platelets is delivery.

• Rapidly progressing symptoms with maternal and fetal deterioration within hours.

• Liver haematoma is a rare and potentially life-threatening complication.

• The prognosis is good if the syndrome is treated early.

• Multidisciplinary teamwork in the ICU setting.