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HELLP Syndrome

HELLP syndrome is a serious disorder of pregnancy of unknown etiology characterized by hemolysis, elevated liver enzymes and low platelet count.


Presentation

The diagnosis of HELLP syndrome is made difficult because the presenting symptoms are vague and non-specific. Approximately 90% of patients present with viral type symptoms, malaise, nausea, and headache, and 65% complain of epigastric pain [7]. Early diagnosis of this disorder is critical to a good outcome so any woman presenting in the third trimester with these symptoms should have a complete blood cell count and liver function tests to rule it out [7]. 

The most common symptoms of HELLP syndrome include [8]:

A majority of women with HELLP syndrome have proteinuria and hypertension, but not all [8]. About half of these patients also have periorbital, upper and lower extremity or pulmonary edema [5].

Diagnosis of HELLP syndrome is based on three criteria:

The physical examination in women with HELLP syndrome may be normal except for right upper quadrant tenderness which is present in about 90% of cases. Edema may also be present but is not significant because it is as common in normal pregnancies [7].

HELLP Syndrome
  • MAIN RESULTS: Liver bleeding was detected in 18 (20.7%) patients with class 1 HELLP syndrome, 24 (27.6%) with class 2 HELLP syndrome, and 12 (13.8%) with class 3 or partial HELLP syndrome.[ncbi.nlm.nih.gov]
  • Women were divided into three groups: HELLP syndrome (n 67), partial HELLP syndrome (one or two but not all three features of HELLP syndrome, n 71), and severe preeclampsia (no features of HELLP syndrome, n 178).[ncbi.nlm.nih.gov]
  • Class 3 HELLP syndrome is considered a clinically significant transitional group.[ncbi.nlm.nih.gov]
  • In women with preeclampsia and the HELLP syndrome several genes in the placenta are deregulated. Preeclampsia and the HELLP syndrome are multiplex genetic diseases.[ncbi.nlm.nih.gov]
Anemia
  • The pregnant woman had APS, hemolytic anemia, elevated liver function and low platelet count (HELLP) syndrome, and eclampsia and had a poor outcome from a second pregnancy.[ncbi.nlm.nih.gov]
  • She also exhibited microangiopathic hemolytic anemia, thrombocytopenia, and elevated liver enzymes (consistent with HELLP syndrome). A biopsy showed acute renal cortical necrosis.[ncbi.nlm.nih.gov]
  • The most frequent signs and symptoms of hepatic rupture were the sudden onset of abdominal pain, acute anemia, and hypotension. Laboratory findings included low platelet count and increased hepatic enzymes. Surgery was performed in 9 cases.[ncbi.nlm.nih.gov]
  • 100, Boulevard du Général Leclerc, 92110 Clichy, France. g.ducarme@gmail.com Abstract Malaria may be complicated by development of thrombocytopenia, elevated liver enzymes, and/or hemolysis, which may be difficult to distinguish from HELLP (hemolytic anemia[ncbi.nlm.nih.gov]
  • It is characterized by microangiopathic hemolytic anemia, elevated liver enzymes by intravascular breakdown of fibrin in hepatic sinusoids and reduction of platelet circulation by its increased consumption.[ncbi.nlm.nih.gov]
Nausea
  • She complained of epigastric pain and nausea. The levels of AST, ALT, and LDH were 539, 560, and 1051 IU/L, respectively; the platelet count was 101 x 109/L. Cesarean section was promptly performed. Intraoperatively, she had a first convulsion.[ncbi.nlm.nih.gov]
  • Patients manifesting this syndrome usually are seen before term (less than 36 weeks' gestation) complaining of malaise (90%), epigastric or right upper-quadrant pain (90%), and nausea or vomiting (50%), and some will have nonspecific viral-syndrome-like[ncbi.nlm.nih.gov]
  • Eclampsia, epigastric pain, nausea and vomiting, significant proteinuria, major maternal morbidity, and stillbirth increased as HELLP syndrome worsened from class 3 to class 1.[ncbi.nlm.nih.gov]
  • Typical clinical symptoms of HELLP syndrome are pain in the right upper quadrant abdomen or epigastric pain, nausea and vomiting. However, this syndrome can present nonspecific symptoms and the diagnosis may be difficult to be established.[ncbi.nlm.nih.gov]
  • Approximately 90% of patients present with viral type symptoms, malaise, nausea, and headache, and 65% complain of epigastric pain.[symptoma.com]
Abdominal Pain
  • Abstract We describe a 32-year-old female with past medical history of preeclampsia, who presented at 29th week of gestation of her second pregnancy with abdominal pain, emesis, and diarrhea.[ncbi.nlm.nih.gov]
  • Hedwig, Steinmetzstrasse 1-3, 93049 Regensburg, Germany. andreas_falkert@yahoo.de Abstract A woman at 16 weeks of gestation was admitted to our perinatal center with unspecific abdominal pain.[ncbi.nlm.nih.gov]
  • Hypertension-induced hepatic disease is a common cause of abdominal pain and liver function test abnormalities in the pregnant patient.[ncbi.nlm.nih.gov]
  • The most frequent signs and symptoms of hepatic rupture were the sudden onset of abdominal pain, acute anemia, and hypotension. Laboratory findings included low platelet count and increased hepatic enzymes. Surgery was performed in 9 cases.[ncbi.nlm.nih.gov]
  • On day 2 postoperatively, she developed a sudden severe colicky upper abdominal pain with tachypnoea, dyspnoea, and tachycardia, and blood pressure (BP) reaching 150/95 mmHg.[ncbi.nlm.nih.gov]
Epigastric Pain
  • CONCLUSION: We recommend that severely ill patients with HELLP syndrome having epigastric pain should undergo CT imaging of the liver.[ncbi.nlm.nih.gov]
  • She complained of epigastric pain and nausea. The levels of AST, ALT, and LDH were 539, 560, and 1051 IU/L, respectively; the platelet count was 101 x 109/L. Cesarean section was promptly performed. Intraoperatively, she had a first convulsion.[ncbi.nlm.nih.gov]
  • Eclampsia, epigastric pain, nausea and vomiting, significant proteinuria, major maternal morbidity, and stillbirth increased as HELLP syndrome worsened from class 3 to class 1.[ncbi.nlm.nih.gov]
  • Typical clinical symptoms of HELLP syndrome are pain in the right upper quadrant abdomen or epigastric pain, nausea and vomiting. However, this syndrome can present nonspecific symptoms and the diagnosis may be difficult to be established.[ncbi.nlm.nih.gov]
  • Approximately 90% of patients present with viral type symptoms, malaise, nausea, and headache, and 65% complain of epigastric pain.[symptoma.com]
Hypertension
  • Severe systolic hypertension ( 160 mm Hg), severe diastolic hypertension ( 110 mm Hg), and hypertensive encephalopathy were significantly more common among women with HELLP than among those with eclampsia alone (P 0.01 for all).[ncbi.nlm.nih.gov]
  • BACKGROUND: Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by hypertension and proteinuria. The HELLP syndrome is the most severe form of PE.[ncbi.nlm.nih.gov]
  • Hypertension-induced hepatic disease is a common cause of abdominal pain and liver function test abnormalities in the pregnant patient.[ncbi.nlm.nih.gov]
  • Recurrent hypertension was observed in 24% of the pregnancies.[ncbi.nlm.nih.gov]
  • CONCLUSIONS: This rare cause of spinal cord injury shows the importance of closely monitoring pregnant patients with hypertension complicated with HELLP syndrome both pre- and postpartum.[ncbi.nlm.nih.gov]
Purpura
  • CONCLUSION: Thrombotic thrombocytopenic purpura can mimic HELLP syndrome late in gestation.[ncbi.nlm.nih.gov]
  • The condition is sometimes misdiagnosed as: Flu or other viral illness Gallbladder disease Hepatitis Idiopathic thrombocytopenic purpura (ITP) Lupus flare Thrombotic thrombocytopenic purpura Symptoms include: Fatigue or feeling unwell Fluid retention[nlm.nih.gov]
  • Among the array of microangiopathies that may occur during pregnancy, HELLP syndrome and thrombotic thrombocytopenic purpura (TTP) produce similar laboratory findings (hemolytic anemia and thrombocytopenia), although neurological symptoms prevail in TTP[ncbi.nlm.nih.gov]
  • Some women may have easy bruising/purpura. On examination, oedema, hypertension and proteinuria are present. Tenderness over the liver can occur.[patient.info]
  • May, Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955-2006, American Journal of Obstetrics and Gynecology, 199, 2, (98), (2008).[doi.org]
Skin Lesion
  • Early recognition is critical, as skin lesions may precede the development of pancreatitis. Often, as in our case, the effects of pancreatitis may be life threatening. Copyright 2011 John Wiley & Sons A/S.[ncbi.nlm.nih.gov]
Headache
  • On the 6th post-cesarean day, she complained severe headache followed by coma. The CT scan revealed the enlargement of both lateral ventricles, indicating the occurrence of obstructive hydrocephalus.[ncbi.nlm.nih.gov]
  • Cesarean section was performed at 28 weeks due to headache, epigastralgia, and severe hypertension. HELLP became evident after delivery. On post-partum day 1, she complained of achromatopsia, stating: "all things look brownish-gray".[ncbi.nlm.nih.gov]
  • The wide overlap in symptoms (headache, malaise, digestive symptoms) does not suggest that symptoms would be effective in differentiating malaria and preeclampsia.[ncbi.nlm.nih.gov]
  • CASE REPORT: Female patient, 36 years old, gestational age of 24 weeks, with hypertensive crisis (BP 180/100mmHg) and severe headache, was admitted to the operating room for a cesarean section after diagnosis of HELLP syndrome.[ncbi.nlm.nih.gov]
  • In contrast, headache and diastolic hypertension were more common among the significantly heavier patients with severe preeclampsia without HELLP syndrome.[ncbi.nlm.nih.gov]
Seizure
  • METHODS: We present a rare case of HELLP syndrome which presented with ICH and further complicated by seizures, disseminated intravascular coagulation, and acute renal failure.[ncbi.nlm.nih.gov]
  • The clinical course was complicated by seizures and acute kidney injury requiring hemodialysis. She also exhibited microangiopathic hemolytic anemia, thrombocytopenia, and elevated liver enzymes (consistent with HELLP syndrome).[ncbi.nlm.nih.gov]
  • The mainstay of therapy is supportive management, including seizure prophylaxis and blood pressure control in patients with hypertension.[ncbi.nlm.nih.gov]
  • Approximately 8 hours after the cesarean section, she developed seizures, followed by evident acute heart and renal failure.[ncbi.nlm.nih.gov]
  • You may also receive: A blood transfusion if bleeding problems become severe Corticosteroid medicines to help the baby's lungs develop faster Medicines to treat high blood pressure Magnesium sulfate infusion to prevent seizures Outcomes are most often[nlm.nih.gov]

Workup

The platelet count is the most reliable indicator of HELLP syndrome. The D-dimer test may be a useful tool for the early identification of patients with preeclampsia who may develop severe HELLP syndrome [7].

In any pregnant woman, HELLP syndrome should be suspected with a significant drop in the platelet count. A positive D-dimer test in patients with preeclampsia has been seen to indicate those who will develop HELLP syndrome as it is a more sensitive to subclinical coagulopathy [7].

Laboratory studies should include [3]:

  • Complete blood cell (CBC) count 
  • Coagulation studies 
  • Peripheral smear for schistocytes, helmet cells, burr cells 
  • Liver function tests: serum aspartate aminotransferase, alanine aminotransferase (AST/ALT) levels
  • Lactate dehydrogenase (LDH) level 
  • Complete metabolic panel 
  • Bilirubin level 
  • Haptoglobin level 
  • Fibrinogen levels

Imaging studies are only recommended when severe liver involvement is suspected by worsening liver function tests. In this case computed tomography, magnetic resonance imaging, or hepatic ultrasound are suggested [3] [7].

Decreased Platelet Count
  • Despite considerable patient variation, most gravid women with HELLP syndrome had decreasing platelet counts until 24 to 48 hours after delivery. Conversely, lactate dehydrogenase concentrations usually peaked 24 to 48 hours post partum.[ncbi.nlm.nih.gov]
Liver Function Tests Abnormal
  • Hypertension-induced hepatic disease is a common cause of abdominal pain and liver function test abnormalities in the pregnant patient.[ncbi.nlm.nih.gov]
Pancreatic Necrosis
  • Although the hemopoetic and hepatic systems are classically involved, we illustrate a case of walled-off pancreatic necrosis occurring in a woman with HELLP syndrome.[ncbi.nlm.nih.gov]
Left Ventricular Hypertrophy
  • Heart rate of 93 beats per minute (bpm) with left atrial diameter (LAD) of 35 mm, left ventricular hypertrophy and inferior vena cava diameter (IVCD) of 8 mm at GW 32 -0/7 decreased to 48 bpm with an expanded IVCD to 25 mm, dilated left atrium (LAD to[ncbi.nlm.nih.gov]

Treatment

Early diagnosis and treatment is critical in the management of HELLP syndrome as delayed intervention increases the mortality and morbidity rates significantly. Maternal mortality rate have been reported to be as high as 25% [3] [7].

The foundation of optimal treatment of HELLP syndrome is supportive care, including seizure prevention and blood pressure control [1]. Women at term should be delivered as soon as possible. Those at less than 34 weeks should be managed conservatively [7]. Severe HELLP syndrome is progressive and sudden maternal deterioration can occur. Delivery is the only effective treatment therapy [3] [8].

Stabilization and initial treatment of HELLP syndrome involve:

  • Treatment to prevent seizures usually includes intravenous magnesium sulfate with a 4 to 6g loading dose over 20 minutes and then 2g per hour as maintenance. This should be continued until 24 hours after delivery [7].
  • Treatment of hypertension: The goal is to keep the systolic blood pressure <160 and the diastolic blood pressure <105. Labetalol and hydralazine are the recommended drugs. Dosing for intravenous hydralazine (Apresoline) is initial small incremental doses of 2.5 to 5mg every 15 to 20 minutes until blood pressure is normal [7].
  • Corticosteroid therapy is controversial [8]. It is theorized that steroid usage may decrease intravascular endothelial injury and prevent further hepatic and platelet dysfunction [3] [7]. Research has shown improvement in blood pressure, urine output, platelet count, and liver function tests [7].
  • Corticosteroid therapy may also decrease fetal morbidity by reducing respiratory distress syndrome and cerebral hemorrhage [3] [6]. 

Patients should be monitored closely once they are stabilized. This is done best in the labor and delivery department of a tertiary health center [5] [8]. Patients close to 34 weeks gestation who have no clinical or laboratory improvement may require immediate delivery [8].

Women with HELLP syndrome whose hypertension is controlled, oliguria responds to fluid management, and have no right upper quadrant or epigastric pain may be eligible for conservative management [7].

Treatment for unstable HELLP syndrome [3] [5] [7]:

The treatment approach is different for each patient and should be based on the estimated gestational age and the condition of the mother and fetus [7].

Prognosis

Symptoms of HELLP syndrome usually resolve rapidly within 24-48 hours of delivery with normal platelet counts by 5 days [3] [5].

Persistence of hemolysis for longer than 72 hours, increasing hepatic or renal failure indicates the potential for life-threatening complications. These require further treatment such as: plasmapheresis, plasma volume expansion, antithrombotic agents, plasma exchange, transfusion, or dialysis [3].

Maternal complications, including disseminated intravascular coagulation, placental abruption and acute renal failure, are common and potentially life-threatening [6] [7].

The recurrence rate of HELLP syndrome with subsequent pregnancies is 2%-27% [7]. Patients also have an increased risk of preeclampsia or pregnancy-induced hypertension, preterm delivery, and placental abruption in future pregnancies [7]. 
Early diagnosis and treatment ensures the best maternal and perinatal outcomes [6] [9].

Etiology

HELLP syndrome was identified in the early 20th century as a subtype of preeclampsia [4]. In 1982 the acronym HELLP was used to describe the primary characteristics of hemolysis, elevated liver enzyme levels and low platelet count [1] [6] [3]. The cause of HELLP syndrome is unknown, although multiple theories have been advanced. HELLP syndrome is a microangiopathic hemolytic anemia resulting in small, diffuse areas of hemorrhage [3].

Risk factors for HELLP syndrome include the following [4] [7]:

  • Maternal age older than 34 years
  • Multiparity
  • White race or European descent
  • History of poor pregnancy outcome [4]

Maternal mortality rates have been reported to be as high as 25% and are dependent on time of diagnosis, maternal health, and availability of advanced medical care [8]. Cerebral hemorrhage is the most common cause of death [8].

Complications of HELLP syndrome include the following [8]:

Fetal morbidity and mortality rates range from 9% to 24% [8]. The usually cause are placental abruption, intrauterine asphyxia, or prematurity [2]. The early diagnosis and treatment of HELLP syndrome is difficult due to the vague, nonspecific signs and symptoms of this disorder [9].

Epidemiology

HELLP syndrome is rare, occurring in approximately 0.1% to 0.6% of all pregnancies. The incidence is higher in patients with preeclampsia occurring in 4%-12% of these patients [6] [7].
HELLP syndrome occurs in weeks 22 to 27, at delivery, or immediately postpartum in 15%-30% of cases [3] [6]. 
The incidence of HELLP syndrome is significantly higher in Caucasians of European descent and women older than 25 years of age. [3]

Mortality rates [6] [3]:

Recurrence in subsequent pregnancies is 4%–19% [7].

Sex distribution
Age distribution

Pathophysiology

The pathology of HELLP syndrome is not well understood. Symptoms of this multisystem disease are a result of abnormal vascular tone, vasospasm and altered coagulation [7] No common precipitating factor has been determined however. Whatever the trigger, it leads to microvascular endothelial injury and platelet activation with the release of thromboxane A and serotonin. This causes a cascade of vasospasm, platelet agglutination, and further endothelial damage [7] [10]. The process only stops with delivery [7].

HELLP syndrome involves a hemolytic anemia where red blood cells destroyed by the small damaged blood vessels. Elevated liver enzyme levels are secondary to obstruction of hepatic blood flow, liver damage, intrahepatic hemorrhage, or possible hepatic rupture [5] [7] [11]. The thrombocytopenia has been attributed to increased consumption and/or destruction of platelets [7].

Many theories have been proposed to explain the pathogenesis, but the true pathology is unknown. One theory regarding the cause of HELLP syndrome is that it is a form of severe preeclampsia, and the pathophysiology is the same. It postulates that there is a release various placental factors due to inadequate placental perfusion during the 16-22 week of pregnancy [5] [12]. This results in hypertension, proteinuria, and increased platelet depletion [13].

Another theory proposes that HELLP syndrome results from the alteration of the maternal-fetal immune balance, causing the symptoms of the disorder [14]. This suggests an inflammatory response targeting the liver [10] [12].

Complications of HELLP syndrome for the mother include [2]:

Complications for the neonate resulting from HELLP syndrome [2]:

Prevention

There is currently no known means of preventing HELLP syndrome. However, early recognition and treatment of this disorder with a multidisciplinary approach can reduce maternal and perinatal morbidity and mortality [1] [4].

Summary

HELLP syndrome is a serious, potentially life-threatening, complication of pregnancy [1] [2]. It is characterized by: (H) hemolysis, (EL) elevated liver enzyme levels, and (LP) low platelet levels [2] [3]. These symptoms give the disorder its name. HELLP syndrome has been associated with poor maternal and neonatal outcomes [2].

Those at highest risk of HELLP syndrome are white, multiparous women over 25 years of age with a poor past pregnancy history. It occurs most often between 27 and 37 weeks gestation [1] [4] [5].

The clinical presentation of HELLP syndrome is often vague leading to initial misdiagnosis and delayed treatment [5] [6]. Patients may present with viral type symptoms, malaise, nausea, vomiting, and headache. Complaints of epigastric or right upper quadrant pain should alert healthcare providers to the possible diagnosis of HELLP syndrome [6].

It is theorized that HELLP is a severe form of preeclampsia. However, while preeclampsia is characterized by gestational hypertension with proteinuria, these symptoms are not always present in HELLP syndrome [1]. Another theory is that HELLP syndrome is a separate disorder [7].

The cause of HELLP syndrome is unknown and there is no known means of prevention [1].

Patient Information

What is HELLP syndrome?

HELLP syndrome is a serious, often life-threatening complication of pregnancy. Its name comes from the three primary features of the disorder: Hemolysis (destruction of red blood cells), Elevated Liver enzymes, and Low Platelet count. HELLP syndrome can result in maternal and fetal morbidity and mortality. It needs to be identified and treated early for the best prognosis.

What are the symptoms of HELLP syndrome?

The symptoms of HELLP syndrome are vague and non-specific making diagnosis difficult. Symptoms include:

What causes HELLP syndrome?

The cause of HELLP syndrome is not known. It is believed to be related to preeclampsia and eclampsia. Symptoms are the result of injury to the lining of the blood vessels with accumulation of platelets. The damaged vessels cause destruction of red blood cells and interrupted blood flow to the liver and kidneys.

Who gets HELLP syndrome?

HELLP syndrome occurs most frequently in Caucasian women, over the age of 25, in their third trimester of pregnancy. Those women who have preeclampsia or who have had previous problem pregnancies are at higher risk.

How is HELLP syndrome diagnosed?
There is no specific diagnostic testing for HELLP syndrome. However, any woman with the above symptoms and a low platelet count and abnormal liver function tests should be further evaluated for the disorder.

How is it treated?

The only truly effective means of treating HELLP syndrome is delivery as soon as possible. Patients must first be stabilized by controlling associated hypertension and preventing the complication of seizures. Pre-term pregnancies may be treated conservatively with antiseizure and antihypertensive medications. Corticosteroids may also be effective in controlling maternal symptoms and complication of fetal immaturity.

What are the complications?

The complications of HELLP syndrome include:

For the mother:

Complications for the neonate:

How can HELLP syndrome be prevented?

There is currently no known means of preventing HELLP syndrome. However, early recognition and treatment of this disorder with a multidisciplinary approach can reduce maternal and perinatal morbidity and mortality.

References

Article

  1. Weinstein L. Syndrome of hemolysis, elevated liver enzymes, and low platelet count: A severe consequence of hypertension in pregnancy. Am J Obstet Gynecol. 1982;142:159.
  2. Harms K, Rath W, Herting E, Kuhn W. Maternal hemolysis, elevated liver enzymes, low platelet count, and neonatal outcome. Am J Perinatol. 1995;12:1-5.
  3. Hay JE. Liver Disease in Pregnancy. Hepatology. 2008; 47(3): 1067-77.
  4. Rahman TM, Wendon J. Severe hepatic dysfunction in pregnancy. Quart J Med. 2002;95:343-352.
  5. Mutter WP, Karumanchi SA. Molecular mechanisms of preeclampsia. Microvasc Res. 2008;75:1-8.
  6. Geary M. The HELLP syndrome. Br J Obstet Gynaecol. 1997;104, 887-891.
  7. Ohara Padden, M. HELLP Syndrome: Recognition and Perinatal Management. Am Fam Physician. 1999;60(3):829-836.
  8. Barton JR, Sibai BM. Diagnosis and management of hemolysis, elevated liver enzymes, and low platelets syndrome. Clin Perinatol. 2004;31:807-33.
  9. Magann EF, Martin JN Jr. Twelve steps to optimal management of HELLP syndrome. Clin Obstet Gynecol. 1999;42:532-538.
  10. Fang CJ, Richards A, Liszewski MK, Kavanagh D, Atkinson JP. Advances in understanding of pathogenesis of aHUS and HELLP. British Journal of Haematology. 2008;143: 336–348.
  11. Widmer M, Villar J, Beniani A, et al. Mapping the theories of preeclampsia and the role of angiogenic factors: A systematic review. Obstet Gynecol. 2007;109:168-173.
  12. Hulstein JJ, van Runnard HPJ, Franx A, Lenting PJ, Bruinse HW, Silence K, et al. Acute activation of the endothelium results in increased levels of active von Willebrand factor in hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. J Thromb Haemost. 2006; 4: 2569–75.
  13. Gyselaers W, Mullens W, Tomsin K, Mesens T, Peeters L. Role of dysfunctional maternal venous hemodynamics in the pathophysiology of pre-eclampsia: a review Ultrasound Obstet Gynecol. 2011; 38: 123–129.
  14. Hulstein JJJ, Van Runnard Heimel PJ, Franx A, . Lenting PJ, Bruinse HW, Silence K, et al. Vascular endothelial growth factor ligands and receptors that regulate human cytotrophoblast survival are dysregulated in severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome. Am J Pathol. 2002;160:1405-23.

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Last updated: 2018-06-22 11:03