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Revisiting HELLP syndrome
PII: S0009-8981(15)30026-7
DOI: doi: 10.1016/j.cca.2015.10.024
Reference: CCA 14149
Please cite this article as: Dusse Luci Maria, Alpoim Patrcia Nessralla, Silva Ju-
liano Teixeira, Rios Danyelle Romana Alves, Brandao Augusto Henriques, Cabral
Antonio Carlos Vieira, Revisiting HELLP syndrome, Clinica Chimica Acta (2015), doi:
10.1016/j.cca.2015.10.024
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Luci Maria Dusse1-PhD
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Patrcia Nessralla Alpoim1- PhD
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Juliano Teixeira Silva1- Pharmacyst
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Danyelle Romana Alves Rios2 -PhD
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Faculdade de Farmcia/Universidade Federal de Minas Gerais/Brazil
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2
Campus Centro Oeste Dona Lindu, Universidade Federal de So Joo Del-
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Rei, Brazil.
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Centro de Medicina Fetal Hospital das Clnicas/ Universidade Federal de
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Minas Gerais/Brazil
Correspondent Author:
Luci Dusse
Faculdade Farmcia/Sala4104
Av.Antnio Carlos,6627
Phone:55313409-6880 FAX:55313409-6985
email:lucidusse@gmail.com
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ABSTRACT
HELLP syndrome was first described in 1982 by Weinstein et al. and the
term HELLP refers to an acronym used to describe the clinical condition that
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leads to hemolysis, elevated liver enzymes and low platelets. The syndrome
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frequency varies from 0.5 to 0.9% pregnancies and manifests preferentially
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between the 27th and 37th weeks of gestation. Approximately 30% of cases
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occur after delivery. Although the etiopathogenesis of this syndrome remains
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unclear, histopathologic findings in the liver include intravascular fibrin deposits
capsular rupture. Typical clinical symptoms of HELLP syndrome are pain in the
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However, this syndrome can present nonspecific symptoms and the diagnosis
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fetus is still uncertain clinical value. In conclusion, three decades after the
diagnosis; Treatment.
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I. Introduction
HELLP syndrome was first described in 1982 by Weinstein et al. and the
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term HELLP refers to an acronym used to describe the clinical condition that
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leads to hemolysis, elevated liver enzymes and low platelets [1]. Weinstein was
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undoubtedly the researcher with the greatest importance to advance the
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recognition of HELLP syndrome. He studied in detail 29 cases that were
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published in 1982 [1] and other 57 cases, published in 1985 [2].
both mother and fetus death, thus being necessary a faster diagnosis and
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II. Etiopathogenesis
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although it can occur in the absence of this disease. This variant sometimes
does not present hypertension, proteinuria and edema. Patients may have a
liver enzymes and finally hemolysis. In 25% of cases, the syndrome was
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Pain in the right upper quadrant around a week before admission was
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0.5% of cases [4].
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Although the etiopathogenesis of this condition remains unclear,
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histopathologic findings in the liver include intravascular fibrin deposits that
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presumably may lead to hepatic sinusoidal obstruction, intrahepatic vascular
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intraparenchymal and subcapsular hemorrhage, and eventually capsular
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rupture [1, 5, 6].
III. Frequency
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manifests before the delivery in 70% of cases and occurs preferentially between
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the 27th and 37th weeks of gestation [4]. Approximately 10% of cases manifest
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before the 27th week and 20% after the 37th [7]. The syndrome affects primarily
usually up to 48 hours, even though some take up to 7 days. In these cases, the
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not associated with these previous symptoms [4, 12]. Although variable, the
excessive weight gain and the presence of generalized edema are signs of
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HELLP development [13].
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IV. Diagnostic criteria
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The diagnosis of the complete form of HELLP syndrome requires the
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presence of symptomatic triad, hemolysis, hepatic changes with increased
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enzymes and thrombocytopenia, as well as severe symptoms, as general
malaise, with or without vomiting, pain in the right upper quadrant of the
abdomen, excessive weight gain and the presence of generalized edema [1, 2,
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13, 14].
pregnant women with pain in the right upper quadrant of the abdomen.
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syndrome [19].
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loss or accumulation in the kidneys and iron excretion, which keeps away the
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iron deleterious actions. This process leads to a pronounced decrease of
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haptoglobin plasma levels, sometimes reaching to undetectable levels, since
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this protein is not produced in response to its consumption [17, 18]. Although
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haptoglobin plasma decrease is an important parameter for the diagnosis of
acute hemolysis, its determination is not usually used for HELLP syndrome
diagnosis [18].
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The elevated liver enzymes reflect injury to the liver microcirculation and
assessment is not routinely performed, and it is thus not used for the diagnosis
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Currently there are two major definitions for diagnosing the HELLP
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bilirubin (20.5mol/L or 1.2mg/100mL) and elevated LDH levels (>600U/L)
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[12, 13]. The Mississippi-Triple Class is based on the nadir of platelets count
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any time during the course of the disease. Class 1 and class 2 are associated
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with hemolysis (LDH>600U/L) and elevated AST levels (70 U/L), while class 3
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(platelet count in class 1: <50x109/L, class 2: 50x109/L -100x109/L and class 3:
only one or two elements of the triad (hemolysis, hepatic changes with
increased enzymes and thrombocytopenia) [7, 13, 23, 26]. It can progress to
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complete form [23, 26]. A partial or full reversal of the syndrome can rarely
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Typical clinical symptoms of HELLP syndrome are pain in the right upper
often report discomfort a few days before the presentation of abdominal pain
[12, 27]. Approximately 30-60% of pregnant women have headache and about
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However, this syndrome can present nonspecific symptoms, which could lead to
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frequent in the livers right lobus [4, 12, 29]. This process is accompanied by
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symptoms such as a sudden beginning, epigastric pain, backache and pain in
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the right shoulder, anemia and hypotension [30, 31]. A low index of suspicion is
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warranted in patients with such symptoms to prompt emergent imaging and to
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maternal and perinatal morbidity and mortality. Hepatic rupture can also occur
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in postpartum [32].
should pay attention to the nuances of the clinical history (pyelonephritis with
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the therapeutic approach may differ and an error or a delayed diagnosis may
other acute diseases. Other clinical conditions that can mimic HELLP syndrome
[16, 33]. AFLP usually occurs between the 30th and 38th weeks of gestation,
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ammonia, liver enzymes (alkaline phosphatase, AST and ALT) and bilirubin are
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present [33-35]. The prolongation of prothrombin time, due to factors II and V
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decreasing, supports the AFLP diagnosis, while hypoglycemia suggests HELLP
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syndromes. Liver ultrasonography may reveal increased echogenicity in severe
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thrombocytopenia and very low or undetectable ADAMTS13 activity [37].
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ADAMTS13 specifically cleaves unusually-large von Willebrand factor (UL-
VWF) multimers under high shear stress, and down-regulates VWF function to
maternal plasma reflect the virtual absence of ADAMTS13, which supports TTP
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[38].
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the complexity and the cost of this exam limit its use. On the other hand,
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VIII. Treatment
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Treatment of HELLP syndrome is based on syndrome symptoms. The
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crisis should be treated with antihypertensive as nifedipine or hydralazine.
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When indicated, prophylaxis with magnesium sulfate should be used in
schemes described in the literature. Patients with gestational age less than 34
which they can be benefited from the use of corticosteroids for fetal lung
both pulmonary maturation of the fetus and the recovery of platelet count of the
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mother is common, but its clinical value remains unclear [41, 43].
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individual outcomes was improved platelet count and this effect was stronger in
morbidity or death was found. Maternal death and severe maternal morbidity
postnatally. They concluded that there was no clear evidence of any effect of
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steroids showed significantly greater improvement in platelet counts, which was
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greater for those receiving dexamethasone than those receiving
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betamethasone. To date, there is insufficient evidence of benefits in terms of
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substantive clinical outcomes to support the routine use of corticosteroids for
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increased rate of recovery in platelet count is considered clinically worthwhile
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[44].
IX. Conclusion
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1980s and are very useful nowadays for pregnant women with HELLP
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and the patient does not appear to be sick. The second one highlights
decreased glycogen stores in the liver and increased circulating insulin. The
third one emphasizes that there is no correlation between platelet count and
liver enzyme levels to diagnose HELLP syndrome. The fourth one shows that all
heartburn and pain in the right upper quadrant during the third trimester of
gestation and these symptoms were mistakenly treated with drugs not indicated
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pregnant women.
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Acknowledgement
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The authors thank FAPEMIG and CNPq/Brazil. LMD is grateful to CNPq Research
Fellowship (302794/2012-3).
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Highlights
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HELLP syndrome is a severe and progressive clinical condition
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Laboratory tests and imaging exams are essential for diagnosis
Etiopathogenesis of this syndrome remains unclear
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There is insufficient evidence to support the routine use of corticosteroids
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for treatment
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