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Official reprint from UpToDate www.uptodate.com 2014
UpToDate
AuthorBaha M Sibai, MD
Section EditorsCharles J Lockwood, MDKeith D Lindor, MD
Deputy EditorVanessa A Barss, MD
HELLP syndrome
All topics are updated as new evidence becomes available and our
peer review process is complete.Literature review current through:
Apr 2014. | This topic last updated: Mar 06, 2014.
INTRODUCTION HELLP is an acronym that refers to a syndrome
characterized by Hemolysis with a microangiopathic blood smear,
Elevated Liver enzymes, and a Low
Platelet count [1]. It probably represents a severe form of
preeclampsia (table 1 and table 2), but the relationship between
the two disorders remains controversial. As many as 15
to 20 percent of patients with HELLP syndrome do not have
antecedent hypertension or proteinuria, leading some authorities to
believe that HELLP is a separate disorder from
preeclampsia [2-4]. Both severe preeclampsia and HELLP syndrome
may be associated with serious hepatic manifestations, including
infarction, hemorrhage, and rupture.
This topic will focus upon the clinical manifestations,
diagnosis, and management of HELLP syndrome. Preeclampsia is
reviewed in detail separately. (See "Preeclampsia:
Clinical features and diagnosis" and "Preeclampsia: Management
and prognosis".)
INCIDENCE HELLP develops in approximately 0.1 to 0.8 percent of
pregnancies overall and in 10 to 20 percent of women with severe
preeclampsia/eclampsia.
RISK FACTORS A previous history of preeclampsia or HELLP is a
risk factor for HELLP syndrome (see 'Recurrence in subsequent
pregnancies' below). Sisters and offspring of
women with a history of HELLP syndrome are also at increased
risk of developing the syndrome [5]. A variety of genetic variants
associated with an increased risk of HELLP
syndrome have been reported, but have no role in clinical
management [6].
In contrast to preeclampsia, nulliparity is not a risk factor
for HELLP syndrome [7]. Half or more of affected patients are
multiparous.
PATHOGENESIS The pathogenesis of HELLP syndrome is unclear. If
it is a form of severe preeclampsia, it likely originates from
aberrant placental development and function.
(See "Pathogenesis of preeclampsia".) As an independent entity,
it has been attributed to abnormal placentation, similar to
preeclampsia, but with greater hepatic inflammation
and greater activation of the coagulation system than in
preeclampsia [6,8,9]. In a case report of a woman with severe early
HELLP syndrome, treatment with eculizumab, a
targeted inhibitor of complement protein C5, was associated with
marked clinical improvement and complete normalization of lab
parameters for 16 days [10]. The authors chose
this intervention based on the hypothesis that
preeclampsia/HELLP is a systemic inflammatory disorder and the
complement cascade is a key mediator, and the observation that
women with mutations in complement regulatory proteins appear to
be at increased risk of severe preeclampsia [11].
In less than 2 percent of patients with HELLP, the underlying
etiology appears to be related to fetal long-chain 3-hydroxyacyl
CoA dehydrogenase (LCHAD) deficiency [12,13]. In
one case series, all six pregnancies with fetal LCHAD deficiency
developed severe maternal liver disease (HELLP or acute fatty liver
of pregnancy [AFLP]) [14]. These
complications probably were not due to chance or maternal
heterozygosity for LCHAD deficiency alone because three other
pregnancies with unaffected fetuses among these
mothers were uncomplicated. In another case series in which 19
fetuses had LCHAD deficiency, 15 mothers (79 percent) developed
AFLP or the HELLP syndrome during their
pregnancies [15]. (See "Acute fatty liver of pregnancy".)
PATIENT PRESENTATION HELLP syndrome has a variable presentation
(table 3). The most common symptom is abdominal pain and tenderness
in the midepigastrium, right
upper quadrant, or below the sternum [16]. Many patients also
have nausea, vomiting, and malaise, which may be mistaken for a
nonspecific viral illness or viral hepatitis,
particularly if the serum aspartate aminotransferase (AST) and
lactate dehydrogenase (LDH) are markedly elevated [17]. Less common
signs and symptoms include headache,
visual changes, jaundice, and ascites. Mistaking abdominal pain,
nausea, vomiting, and malaise for viral illness is a common pitfall
that has resulted in maternal death or severe
morbidity [18].
Hypertension (blood pressure 140/90 mmHg) and proteinuria are
present in approximately 85 percent of cases, but it is important
to remember that either or both may be absent
in women with otherwise severe HELLP syndrome [19].
Signs and symptoms typically develop between 28 and 36 weeks of
gestation, but second trimester or postpartum onset is also common.
In an illustrative series of 437 women
who had 442 pregnancies complicated by the HELLP syndrome, 70
percent occurred prior to delivery [16]. Of these patients,
approximately 80 percent were diagnosed prior to 37
weeks of gestation and fewer than 3 percent developed the
disease between 17 and 20 weeks of gestation. The disease presented
postpartum in 30 percent, usually within 48
hours of delivery, but occasionally as long as 7 days after
birth. Only 20 percent of postpartum patients with HELLP had
evidence of preeclampsia antepartum.
Serious maternal morbidity may be present at initial
presentation or develop shortly thereafter. This includes
disseminated intravascular coagulation (DIC), abruptio
placentae,
acute renal failure, pulmonary edema, subcapsular or
intraparenchymal liver hematoma, and retinal detachment (see
'Maternal outcome' below) [16].
Bleeding related to thrombocytopenia is an unusual
presentation.
DIAGNOSIS The diagnosis of HELLP syndrome is based upon the
presence of all of the laboratory abnormalities comprising its name
(hemolysis with a microangiopathic
blood smear, elevated liver enzymes, and low platelet count) in
a pregnant woman. Thus, laboratory work-up should include [19]:
In addition, we obtain a serum creatinine concentration and
urine protein to creatinine ratio.
We suggest obtaining these laboratory tests in women with new
onset hypertension and/or characteristic symptoms (right upper
quadrant/epigastric pain, nausea, vomiting,
fatigue or malaise) in the second half of pregnancy or first
postpartum week.
Pregnant/postpartum women who have some of the typical
laboratory abnormalities but do not meet all of the laboratory
criteria described below are considered to have partial
HELLP syndrome [7].
Laboratory criteria Precise criteria for HELLP are necessary for
research purposes and for predicting maternal complications. We
require the presence of all of the following
criteria to diagnose HELLP (Tennessee classification) [16]:
These thresholds were chosen, in part, to avoid problems related
to differences in assays used to measure liver enzymes, which may
result in an elevated value in one hospital
that is near normal in another. We do not include elevated
lactate dehydrogenase (LDH) in the laboratory criteria for HELLP
syndrome because it is a nonspecific finding
associated with both hemolysis and liver disease.
As discussed above, women who do not meet all of the above
laboratory abnormalities are considered to have partial HELLP
syndrome. However, these patients may progress to
complete expression of HELLP syndrome.
There is no consensus regarding the laboratory criteria
diagnostic of HELLP syndrome. A common alternative (Mississippi
classification) used to define HELLP syndrome is
Complete blood count with platelet count
Peripheral smear
Aspartate aminotransferase (AST), bilirubin
Microangiopathic hemolytic anemia with characteristic
schistocytes (also called helmet cells) on blood smear (picture 1).
Other signs suggestive of hemolysis include an
elevated indirect bilirubin level and a low serum haptoglobin
concentration (25 mg/dL).
Platelet count 100,000 cells/microL
Total bilirubin 1.2 mg/dL (20.52 micromol/L)
Serum AST 70 IU/L. Some investigators obtain alanine
aminotransferase (ALT) levels instead of, or in addition to, AST
levels. An advantage of the AST is that it is a single
test that reflects both hepatocellular necrosis and red cell
hemolysis.
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[20,21]:
Differential diagnosis HELLP syndrome may occasionally be
confused with other diseases complicating pregnancy: acute fatty
liver of pregnancy (AFLP), gastroenteritis,
hepatitis, appendicitis, gallbladder disease, immune
thrombocytopenia (ITP), lupus flare, antiphospholipid syndrome,
hemolytic-uremic syndrome (HUS), or thrombotic
thrombocytopenic purpura (TTP), and nonalcoholic fatty liver
disease (table 4) [19,22]. (See individual topic reviews on these
subjects).
In one series of 46 women who developed liver disease during
pregnancy severe enough to require admission to a liver failure
unit, 70 percent had acute fatty liver and 15 percent
had HELLP [23]. Most of the remaining patients had liver disease
that was unrelated to pregnancy.
Acute fatty liver of pregnancy The clinical presentation of AFLP
commonly includes nausea and vomiting, abdominal pain, malaise,
polydipsia/polyuria, jaundice/dark
urine, encephalopathy, and hypertension/preeclampsia [24]. HELLP
may be difficult to distinguish clinically from AFLP since both
occur at the same time in gestation and share
several clinical features (figure 1). In fact, in one study
approximately half of AFLP patients based on the Swansea criteria
(which identify the most severe spectrum of the disease)
also fulfilled criteria for HELLP syndrome [25]. (See "Acute
fatty liver of pregnancy", section on 'Clinical
manifestations'.)
It is important to differentiate between the two disorders
because women with AFLP can rapidly develop liver failure and
encephalopathy. Additional laboratory testing can be
helpful: prolongation of the prothrombin (PT) and activated
partial thromboplastin time (aPTT), severe hypoglycemia, and
elevated creatinine concentration are more common in
women with AFLP than in those with HELLP. Hypertension is more
common in HELLP than in AFLP (in one review: 80 to 100 percent of
cases versus 26 to 70 percent of cases
[24]).
Of note, women with AFLP are more likely than women with HELLP
to have offspring with an inherited defect in mitochondrial
beta-oxidation of fatty acids, such as long-chain 3-
hydroxyacyl-coenzyme A dehydrogenase deficiency, short-chain
acyl-coenzyme A dehydrogenase deficiency, or carnitine
palmitoyltransferase I deficiency [12,13,15,26,27].
However, this information is not typically available during
differential diagnosis, and is not highly sensitive or specific.
(See "Acute fatty liver of pregnancy", section on
'Pathogenesis'.)
AFLP can be confirmed by diagnostic liver biopsy, but this is
rarely performed because the clinical diagnosis is usually
reasonably certain, the information gained would not
change management (ie, delivery of the fetus), and the procedure
exposes the mother and pregnancy to additional risks (picture 2).
Furthermore, AFLP and HELLP share several
common histological features [24]. (See "Acute fatty liver of
pregnancy", section on 'Liver biopsy'.)
Thrombotic microangiopathy Thrombocytopenia, anemia, and renal
failure occurring late in pregnancy can also occur in HUS and TTP
[20,28-31]. TTP-HUS should be
considered in all pregnant women with severe thrombocytopenia,
severe anemia, and elevated LDH levels with minimal elevation of
AST (table 4) [32]. The distinction between TTP-
HUS and severe preeclampsia or HELLP is important for
therapeutic and prognostic reasons. However, the clinical and
histologic features are so similar that establishing the
correct diagnosis is often difficult; furthermore, these
disorders may occur concurrently. (See "Diagnosis of thrombotic
thrombocytopenic purpura-hemolytic uremic syndrome in
adults".)
Time of onset may suggest one disorder over the other. The onset
of TTP tends to be earlier in gestation than the onset of
preeclampsia or HELLP: about 12 percent of TTP in
pregnancy occurs in the first trimester, 56 percent in the
second trimester, and 33 percent in the third trimester/postpartum,
whereas preeclampsia-HELLP does not occur before
20 weeks of gestation and most cases are diagnosed in the third
trimester [33]. A history of proteinuria and hypertension prior to
onset of hemolysis, liver abnormalities, and
thrombocytopenia favor the diagnosis of preeclampsia.
Laboratory studies are most helpful for distinguishing between
TTP-HUS and HELLP as the coagulation abnormalities in these
disorders are different.
MANAGEMENT
Initial approach After the diagnosis is confirmed, the initial
steps in management are to stabilize the mother, assess the fetal
condition, and decide whether prompt delivery is
indicated. Pregnancies less than 34 weeks of gestation, and
those in which the mother is unstable, should be managed in
consultation with a maternal-fetal specialist.
Antihypertensive drugs are used to treat severe hypertension.
Hypertension can usually be controlled with labetalol, hydralazine,
or nifedipine or, in severe cases, with sodium
nitroprusside [1]. The approach to antihypertensive therapy is
the same as that for preeclampsia. (See "Management of hypertension
in pregnant and postpartum women", section
on 'Preeclampsia'.)
Magnesium sulfate is given intravenously to patients on the
labor and delivery unit to prevent convulsions, and for
fetal/neonatal neuroprotection in pregnancies between 24 and 32
weeks of gestation. (See "Preeclampsia: Management and
prognosis", section on 'Magnesium regimen and monitoring' and
"Neuroprotective effects of in utero exposure to
magnesium sulfate".)
Timing of delivery The cornerstone of therapy is delivery.
Delivery is curative and the only effective treatment. There is
consensus among experts that prompt delivery is
indicated after maternal stabilization for any of the following
[19,35]:
Role of expectant management We do not manage patients with
HELLP syndrome expectantly at any gestational age and consider this
approach for more than 48
hours investigational. There are few studies on the outcome of
expectant management of HELLP syndrome. In these studies, the
laboratory abnormalities of HELLP syndrome
reversed in a subset of patients managed expectantly and serious
maternal complications were uncommon with careful maternal
monitoring and timely intervention. However, the
aim of expectant management is to improve neonatal morbidity and
mortality. There is no evidence demonstrating improvement in
overall perinatal outcome with expectant
management compared with pregnancies delivered after a course of
corticosteroids, and no maternal benefits from expectant
management. The following studies support our
approach:
Hemolysis documented by an increased LDH level and progressive
anemia
Hepatic dysfunction documented by an LDH level >600 IU/L,
elevated liver enzymes documented by AST >40 IU/L, ALT>40
IU/L, or both
Thrombocytopenia documented by a platelet nadir less than
150,000 cells/mm. Thrombocytopenia is subclassified as class one
HELLP syndrome: platelet nadir 50,000
cells/mm, class two HELLP syndrome: platelet nadir 100,000
cells/mm, or class three HELLP syndrome: platelet nadir 150,000
cells/mm.
HELLP is associated with thrombocytopenia and, in severe cases,
there may be disseminated intravascular coagulation (DIC) with the
attendant prolongation of the PT and
aPTT, and reductions in the plasma concentrations of factors V
and VIII. In contrast, TTP-HUS is associated with isolated platelet
consumption; thus, although
thrombocytopenia is seen, the other findings are typically
absent.
The percentage of schistocytes on peripheral smear is often
higher in TTP (2 to 5 percent) than in HELLP (less than 1 percent)
[32].
Von Willebrand factor-cleaving protease (ADAMTS-13) activity
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Pregnancies less than 34 weeks of gestation When both the
maternal and fetal status are reassuring, we administer a course of
corticosteroids before delivering
pregnancies complicated by HELLP syndrome at less than 34 weeks
of gestation [19,35]. Although a short delay in delivery for
corticosteroid administration appears to be safe
[38], we do not advise attempts to delay delivery beyond 48
hours because disease progression usually occurs, sometimes with
rapid maternal deterioration. (See "Antenatal
corticosteroid therapy for reduction of neonatal morbidity and
mortality from preterm delivery" and 'Role of expectant management'
above.)
Indications for platelet transfusion Actively bleeding patients
with thrombocytopenia should be transfused with platelets. Platelet
transfusion may be indicated to prevent
excessive bleeding during delivery if the platelet count is less
than 20,000 cells/microL, but the threshold for prophylactic
platelet transfusion in this setting is controversial. The
decision depends on patient specific factors; consultation with
the hematology service may be helpful.
If cesarean delivery is planned, platelet transfusion may be
required. Some experts recommend platelet transfusion to achieve a
preoperative platelet count greater than 40,000 to
50,000 cells/microL [19], but the minimum count before a
neuraxial procedure is controversial and depends on factors in
addition to platelet concentration. (See "Adverse effects of
neuraxial analgesia and anesthesia for obstetrics", section on
'Neuraxial analgesia and low platelets' and "Clinical and
laboratory aspects of platelet transfusion therapy", section
on 'Preparation for an invasive procedure'.)
Route of delivery Vaginal delivery is desirable for women in
labor or with ruptured membranes and a vertex presenting infant,
regardless of gestational age. Labor can be
induced in women with favorable cervices or pregnancies at least
30 to 32 weeks of gestation. Cesarean delivery is performed for the
usual obstetrical indications (eg, breech,
nonreassuring fetal status). However, we feel cesarean delivery
is probably preferable in pregnancies less than 30 to 32 weeks of
gestation if the cervix is unfavorable for induction,
especially if there are signs of fetal compromise (growth
restriction, abruptio placenta, oligohydramnios). Induction of
these pregnancies, even with use of cervical ripening agents,
generally has a high failure rate and is often prolonged,
thereby potentially exposing the mother and fetus to a higher risk
of complications from severe HELLP syndrome. (See
"Induction of labor".)
Because of the high risk of subfascial and wound hematoma in
these women, some surgeons place a subfascial drain at cesarean
delivery and leave the incision open for the first
48 postoperative hours [4].
Anesthesia/analgesia Opioids administered intravenously provide
some pain relief without risk of maternal bleeding, which may occur
with intramuscular administration or with
placement of neuraxial anesthesia, removal of a neuraxial
catheter, or placement of a pudendal nerve block. However, there is
no contraindication to perineal infiltration of an
anesthetic for performing an episiotomy or repairing the
perineum. (See "Pharmacologic management of pain during labor and
delivery".)
Role of dexamethasone for treatment of HELLP We do not treat
HELLP syndrome with steroids. Initial observational studies and
small randomized trials suggested use of
glucocorticoids may be associated with more rapid improvement in
laboratory and clinical parameters [39-42]. These findings were not
supported by subsequent large, well-
designed randomized, double-blind, placebo-controlled clinical
trials evaluating the use of dexamethasone to improve maternal
outcome in patients with HELLP syndrome [43,44].
In addition, a Cochrane review of 11 trials comparing
corticosteroids with placebo/no treatment in women with HELLP
syndrome found no difference between groups in rates of
maternal death, maternal death or severe maternal morbidity, or
perinatal/infant death and concluded there was no clear evidence of
benefit on substantive clinical outcomes [45].
Despite these findings, some investigators continue to recommend
use of dexamethasone in patients with platelet counts less than
100,000 cells/microL based on their clinical
experience and relatively consistent findings from multiple
observational studies and small randomized trials [46].
Suspected hepatic hematoma or infarction Marked elevations in
serum aminotransferases are not typical of uncomplicated HELLP;
however, when they occur, the
possibility of hepatic infarction, subcapsular hematoma, or an
unrelated etiology (eg, viral hepatitis) should be considered.
Imaging tests, particularly computed tomography (CT) or magnetic
resonance imaging (MRI), are useful when complications such as
hepatic infarction, hematoma, or rupture are
suspected because of sudden severe right upper quadrant
abdominal pain, which may be associated with shoulder pain, neck
pain, and/or hypotension [47,48]. In one series of 33
women with HELLP and these symptoms, imaging the liver revealed
abnormal findings in 15 (45 percent) patients [47]. The most common
abnormalities were subcapsular
hematoma and intraparenchymal hemorrhage (image 1 and image
2).
Management of hepatic complications
Hepatic hematoma and rupture HELLP may be complicated by hepatic
rupture with development of a hematoma beneath Glisson's capsule
[16,47,49,50]. Histology
of the liver adjacent to the rupture shows periportal hemorrhage
and fibrin deposition, along with a neutrophilic infiltrate,
suggestive of hepatic preeclampsia [16]. The hematoma
may remain contained, or rupture, with resulting hemorrhage into
the peritoneal cavity (image 3). A hepatic hematoma rarely occurs
in the apparent absence of preeclampsia or
HELLP [51].
Women who develop a hepatic hematoma typically have epigastric
pain and many have severe thrombocytopenia, shoulder pain, nausea,
and vomiting [47]. If hepatic rupture
occurs, swelling of the abdomen from hemoperitoneum and shock
rapidly ensue. The aminotransferases are usually modestly elevated,
but values of 4000 to 5000 IU/L can
occasionally be seen. Imaging using CT or MRI is more dependable
than ultrasonography for detecting these lesions (image 4 and image
3) [47].
The management of a contained hematoma is to support the patient
with volume replacement and blood transfusion, as needed. If the
size of the hematoma remains stable and
her laboratory abnormalities are resolving, the patient may be
discharged home with outpatient follow-up. It may take months for
the hematoma to resolve completely [47].
Percutaneous embolization of the hepatic arteries is a
reasonable first-line therapy of hepatic rupture in women who are
hemodynamically stable [52,53]. Surgical intervention is
indicated if there is hemodynamic instability, persistent
bleeding, increasing pain, or continued expansion of the hematoma
[54]. A team experienced in liver trauma surgery
should be consulted [55]. Operative management includes packing,
drainage, hepatic artery ligation, and/or resection of affected
areas of the liver. For patients with intractable
hemorrhage despite these interventions, administration of
recombinant factor VIIa [56] and liver transplantation [57-60] have
been successful in case reports.
Patients who survive have no hepatic sequelae.
Hepatic infarction Hepatic infarction is rare in HELLP syndrome
and is usually associated with an underlying procoagulant state,
particularly the antiphospholipid
syndrome [61-65]. Clinical findings include marked elevation in
serum aminotransferases (usually 1000 to 2000 IU/L or higher) with
right upper quadrant pain and fever; infarction
can be followed by hemorrhage. The diagnosis is supported by
characteristic hepatic imaging (MRI or CT). (See "Clinical
manifestations of the antiphospholipid syndrome" and
"Ischemic hepatitis, hepatic infarction, and ischemic
cholangiopathy".)
POSTPARTUM COURSE Laboratory values may initially worsen
following delivery. The time course of recovery from HELLP was
evaluated in a series of 158 women with the
disease [20]. Decreasing platelet counts continued until 24 to
48 hours after delivery, while serum LDH concentration usually
peaked 24 to 48 hours postpartum. In all patients
who recovered, a platelet count greater than 100,000
cells/microL was achieved spontaneously by the sixth postpartum day
or within 72 hours of the platelet nadir. An upward
trend in platelet count and a downward trend in LDH
concentration should be seen by the fourth postpartum day in the
absence of complications. Others have reported similar
findings [66].
In the first trial, a total of 132 women over 20 weeks of
gestation with HELLP syndrome (60 antepartum, 72 postpartum) were
randomly assigned to receive either
dexamethasone (10 mg intravenously every 12 hours until delivery
and 3 additional doses after delivery) or placebo; postpartum women
only received the postpartum doses
or placebo. All patients had platelet counts less than 100,000
cells/microL, aspartate aminotransferase (AST) >70 IU/L and
lactate dehydrogenase (LDH) >600 IU/L. The
major findings of this trial were:
Dexamethasone did not reduce the duration of hospitalization,
the rate of platelet or fresh frozen plasma transfusion, or
maternal complications (acute renal failure,
pulmonary edema).
The time of recovery of laboratory tests was not shortened by
treatment.
However, subgroup analysis noted that patients with severe HELLP
(platelet count
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Recovery can be delayed in women with particularly severe
disease, such as those with disseminated intravascular coagulation
(DIC), platelet count less than 20,000 cells/microL,
renal dysfunction, or ascites [19,67]. These women are at risk
of developing pulmonary edema and renal failure.
OUTCOME AND PROGNOSIS HELLP syndrome is associated with a
variety of maternal morbidities, which can rarely result in a fatal
outcome. The risk of serious morbidity
correlates with increasing severity of maternal symptoms and
laboratory abnormalities [46].
Maternal outcome Following the delivery, maternal symptoms and
signs begin to improve within 48 hours, but a protracted course is
possible.
The outcome for mothers with HELLP is generally good; however,
serious complications are relatively common. In our series of 437
women with HELLP syndrome at a tertiary
care facility, the following complications were observed
[16]:
In addition, 55 percent of the patients required transfusions
with blood or blood products, and 2 percent required laparotomies
for major intraabdominal bleeding. Four women (1
percent) died.
These complications are interdependent: abruptio placenta is a
common obstetrical etiology of DIC, which, in turn, may induce
acute renal failure. Acute renal failure may lead to
pulmonary edema.
Additional complications that have been reported in other series
include: adult respiratory distress syndrome, sepsis, and stroke
[7,21]. Wound complications secondary to
bleeding and hematomas are common in women with
thrombocytopenia.
Although most liver function tests (aspartate aminotransferase
[AST], lactate dehydrogenase [LDH], and conjugated bilirubin)
return to normal postpartum, in one report, total
bilirubin levels were elevated in 11 (20 percent) of the women
who had liver function tests checked 3 to 101 months after delivery
[68].
HELLP syndrome with or without renal failure does not affect
long-term renal function [69,70].
Recurrence in subsequent pregnancies Data defining the
recurrence risk of HELLP syndrome are sparse given the relatively
low incidence of the disorder. The risk of
recurrent HELLP is low (2 to 6 percent), but the risk of
preeclampsia in a subsequent pregnancy is high (>20 percent),
and even higher (>50 percent) among women with second
trimester HELLP.
Prevention There is no evidence that any therapy prevents
recurrent HELLP syndrome, but data are limited. Use of low dose
aspirin for prevention of preeclampsia is
discussed separately. (See "Prevention of preeclampsia", section
on 'Antiplatelet agents'.)
Fetal/neonatal outcome Fetal/neonatal and long-term prognosis
are most strongly associated with gestational age at delivery and
birthweight [76-84]. Maternal laboratory
parameters do not predict fetal mortality. Prematurity is common
(70 percent; with 15 percent of births before 27 weeks) [76], and
may be complicated by intrauterine growth
restriction and sequelae of abruptio placenta [77]. The overall
perinatal mortality is 7 to 20 percent; prematurity, intrauterine
growth restriction, and abruptio placentae are the
leading causes of perinatal death [19]. Leukopenia, neutropenia,
and thrombocytopenia may be observed, but appear to be related to
intrauterine growth restriction, prematurity,
and maternal hypertension [78]. Maternal HELLP does not affect
fetal/neonatal liver function.
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SUMMARY AND RECOMMENDATIONS
Management recommendations
Disseminated intravascular coagulation (DIC) 21 percent
Abruptio placentae 16 percent
Acute renal failure 8 percent
Pulmonary edema 6 percent
Subcapsular liver hematoma 1 percent
Retinal detachment 1 percent
In three series including almost 400 pregnancies in women with a
history of this syndrome, the rate of recurrence was 2 to 6 percent
[71-73]. However, recurrence rates
(mostly partial HELLP syndrome) of 24 to 27 percent have also
been reported [31,74].
Rare cases of recurrent hepatic rupture in a subsequent
pregnancy have been reported [49,75].
Women with a history of HELLP syndrome are at high risk for
developing preeclampsia in a subsequent pregnancy [71,72,74]. In
one series of 152 such women with 212
subsequent pregnancies, the incidence of preeclampsia varied
from 19 percent in normotensive women to 75 percent in those with
underlying hypertension [71]. Another
report was limited to 48 women with second trimester HELLP
syndrome who had 62 subsequent pregnancies that progressed beyond
20 weeks of gestation [72].
Preeclampsia occurred in 27 of 52 subsequent pregnancies (52
percent) in normotensive women and 7 of 10 pregnancies (70 percent)
in women with chronic hypertension.
th th
th th
Basics topic (see "Patient information: HELLP syndrome (The
Basics)" and "Patient information: High blood pressure and
pregnancy (The Basics)")
HELLP syndrome (hemolysis with a microangiopathic blood smear,
elevated liver enzymes, and low platelet count) develops in 70
IU/L.
The outcome for mothers with HELLP syndrome is generally good,
but serious complications such as abruptio placentae, acute renal
failure, subcapsular liver hematoma,
pulmonary edema, and retinal detachment may occur. Future
pregnancies are at increased risk of HELLP or preeclampsia. (See
'Maternal outcome' above and 'Recurrence
in subsequent pregnancies' above.)
After the diagnosis is confirmed, the initial steps in
management are to stabilize the mother, assess the fetal condition,
and decide whether prompt delivery is indicated.
Severe hypertension is treated with antihypertensive therapy and
magnesium sulfate is given to prevent convulsions and for
neuroprotection of fetuses/neonates at 24 to 32
weeks of gestation. (See 'Initial approach' above.)
HELLP syndrome complicated by multiorgan dysfunction,
disseminated intravascular coagulation (DIC), pulmonary edema,
liver hemorrhage or infarction, renal failure,
abruptio placenta or nonreassuring fetal status is an indication
for prompt delivery regardless of gestational age. (See 'Timing of
delivery' above.)
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31. Sullivan CA, Magann EF, Perry KG Jr, et al. The recurrence
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32. Stella CL, Dacus J, Guzman E, et al. The diagnostic dilemma
of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in
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tertiary hospitals. Am J Obstet Gynecol 2009; 200:381.e1.
33. Martin JN Jr, Bailey AP, Rehberg JF, et al. Thrombotic
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34. Lattuada A, Rossi E, Calzarossa C, et al. Mild to moderate
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35. American College of Obstetricians and Gynecologists' Task
Force on Hypertension in Pregnancy. Hypertension in pregnancy.
Obstet Gynecol 2013; 122:1122.
36. Visser W, Wallenburg HC. Temporising management of severe
pre-eclampsia with and without the HELLP syndrome. Br J Obstet
Gynaecol 1995; 102:111.
37. van Pampus MG, Wolf H, Westenberg SM, et al. Maternal and
perinatal outcome after expectant management of the HELLP syndrome
compared with pre-eclampsiawithout HELLP syndrome. Eur J Obstet
Gynecol Reprod Biol 1998; 76:31.
38. Fitzpatrick KE, Hinshaw K, Kurinczuk JJ, Knight M. Risk
factors, management, and outcomes of hemolysis, elevated liver
enzymes, and low platelets syndrome andelevated liver enzymes, low
platelets syndrome. Obstet Gynecol 2014; 123:618.
39. O'Brien JM, Shumate SA, Satchwell SL, et al. Maternal
benefit of corticosteroid therapy in patients with HELLP
(hemolysis, elevated liver enzymes, and low platelet
count)syndrome: impact on the rate of regional anesthesia. Am J
Obstet Gynecol 2002; 186:475.
40. Matchaba P, Moodley J. Corticosteroids for HELLP syndrome in
pregnancy. Cochrane Database Syst Rev 2004; :CD002076.
41. Isler CM, Barrilleaux PS, Magann EF, et al. A prospective,
randomized trial comparing the efficacy of dexamethasone and
betamethasone for the treatment of antepartum
For pregnancies 34 weeks of gestation, we recommend delivery
rather than expectant management (Grade 1C). In this population,
the potential risks of preterm birth are
outweighed by the risks associated with HELLP syndrome. (See
'Timing of delivery' above.)
For pregnancies less than 34 weeks of gestation in which
maternal and fetal status are reassuring, we suggest delivery after
a course of corticosteroids to accelerate fetal
pulmonary maturity rather than expectant management or prompt
delivery (Grade 2C). Although the laboratory abnormalities of HELLP
syndrome will reverse in a subgroup
of patients managed expectantly and serious maternal
complications are uncommon with careful maternal monitoring,
overall perinatal outcome is not improved with
expectant management. (See 'Pregnancies less than 34 weeks of
gestation' above.)
For gestations less than 30 to 32 weeks with an unfavorable
cervix, we suggest cesarean delivery to avoid a potentially long
induction (Grade 2C). (See 'Route of delivery'
above.)
We recommend not giving dexamethasone for treatment of HELLP
syndrome (Grade 1B). Dexamethasone does not accelerate resolution
of laboratory abnormalities or
reduce the risk of maternal complications. (See 'Role of
dexamethasone for treatment of HELLP' above.)
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HELLP (hemolysis, elevated liver enzymes, and low platelet
count) syndrome. Am J Obstet Gynecol 2001; 184:1332.
42. Martin JN Jr, Thigpen BD, Rose CH, et al. Maternal benefit
of high-dose intravenous corticosteroid therapy for HELLP syndrome.
Am J Obstet Gynecol 2003; 189:830.
43. Fonseca JE, Mndez F, Catao C, Arias F. Dexamethasone
treatment does not improve the outcome of women with HELLP
syndrome: a double-blind, placebo-controlled,randomized clinical
trial. Am J Obstet Gynecol 2005; 193:1591.
44. Katz L, de Amorim MM, Figueiroa JN, Pinto e Silva JL.
Postpartum dexamethasone for women with hemolysis, elevated liver
enzymes, and low platelets (HELLP)syndrome: a double-blind,
placebo-controlled, randomized clinical trial. Am J Obstet Gynecol
2008; 198:283.e1.
45. Woudstra DM, Chandra S, Hofmeyr GJ, Dowswell T.
Corticosteroids for HELLP (hemolysis, elevated liver enzymes, low
platelets) syndrome in pregnancy. CochraneDatabase Syst Rev 2010;
:CD008148.
46. Martin JN Jr, Rose CH, Briery CM. Understanding and managing
HELLP syndrome: the integral role of aggressive glucocorticoids for
mother and child. Am J ObstetGynecol 2006; 195:914.
47. Barton JR, Sibai BM. Hepatic imaging in HELLP syndrome
(hemolysis, elevated liver enzymes, and low platelet count). Am J
Obstet Gynecol 1996; 174:1820.
48. Nunes JO, Turner MA, Fulcher AS. Abdominal imaging features
of HELLP syndrome: a 10-year retrospective review. AJR Am J
Roentgenol 2005; 185:1205.
49. Greenstein D, Henderson JM, Boyer TD. Liver hemorrhage:
recurrent episodes during pregnancy complicated by preeclampsia.
Gastroenterology 1994; 106:1668.
50. Wicke C, Pereira PL, Neeser E, et al. Subcapsular liver
hematoma in HELLP syndrome: Evaluation of diagnostic and
therapeutic options--a unicenter study. Am J ObstetGynecol 2004;
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51. Schwartz ML, Lien JM. Spontaneous liver hematoma in
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52. Rinehart BK, Terrone DA, Magann EF, et al.
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53. Grand'Maison S, Sauv N, Weber F, et al. Hepatic rupture in
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54. Wilson RH, Marshall BM. Postpartum rupture of a subcapsular
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55. Stevenson JT, Graham DJ. Hepatic hemorrhage and the HELLP
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56. Merchant SH, Mathew P, Vanderjagt TJ, et al. Recombinant
factor VIIa in management of spontaneous subcapsular liver hematoma
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57. Erhard J, Lange R, Niebel W, et al. Acute liver necrosis in
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58. Hunter SK, Martin M, Benda JA, Zlatnik FJ. Liver transplant
after massive spontaneous hepatic rupture in pregnancy complicated
by preeclampsia. Obstet Gynecol 1995;85:819.
59. Araujo AC, Leao MD, Nobrega MH, et al. Characteristics and
treatment of hepatic rupture caused by HELLP syndrome. Am J Obstet
Gynecol 2006; 195:129.
60. Zarrinpar A, Farmer DG, Ghobrial RM, et al. Liver
transplantation for HELLP syndrome. Am Surg 2007; 73:1013.
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62. Alsulyman OM, Castro MA, Zuckerman E, et al. Preeclampsia
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antiphospholipid syndrome. Obstet Gynecol 1996;88:644.
63. Seige M, Schweigart U, Moessmer G, et al. Extensive hepatic
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64. Pauzner R, Dulitzky M, Carp H, et al. Hepatic infarctions
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65. Chou MM, Chen YF, Kung HF, et al. Extensive hepatic
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Taiwan J Obstet Gynecol 2012; 51:418.
66. Hupuczi P, Nagy B, Sziller I, et al. Characteristic
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67. Martin JN Jr, Blake PG, Lowry SL, et al. Pregnancy
complicated by preeclampsia-eclampsia with the syndrome of
hemolysis, elevated liver enzymes, and low plateletcount: how rapid
is postpartum recovery? Obstet Gynecol 1990; 76:737.
68. Knapen MF, van Altena AM, Peters WH, et al. Liver function
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69. Jacquemyn Y, Jochems L, Duiker E, et al. Long-term renal
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70. Drakeley AJ, Le Roux PA, Anthony J, Penny J. Acute renal
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71. Sibai BM, Ramadan MK, Chari RS, Friedman SA. Pregnancies
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and low platelets): subsequentpregnancy outcome and long-term
prognosis. Am J Obstet Gynecol 1995; 172:125.
72. Chames MC, Haddad B, Barton JR, et al. Subsequent pregnancy
outcome in women with a history of HELLP syndrome at < or = 28
weeks of gestation. Am J ObstetGynecol 2003; 188:1504.
73. van Pampus MG, Wolf H, Mayruhu G, et al. Long-term follow-up
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74. Habli M, Eftekhari N, Wiebracht E, et al. Long-term maternal
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75. Wst MD, Bolte AC, de Vries JI, et al. Pregnancy outcome
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76. Abramovici D, Friedman SA, Mercer BM, et al. Neonatal
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77. Sibai BM, Spinnato JA, Watson DL, et al. Pregnancy outcome
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78. Harms K, Rath W, Herting E, Kuhn W. Maternal hemolysis,
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79. Singhal N, Amin HJ, Pollard JK, et al. Maternal haemolysis,
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81. Gortner L, Pohlandt F, Bartmann P, et al. Short-term outcome
in infants with birth weights less than 1750 g born to mothers with
HELLP syndrome. J Perinat Med 1992;20:25.
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84. Guzel AI, Kuyumcuoglu U, Celik Y. Are maternal and fetal
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Gynecol Obstet 2011; 283:1227.
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GRAPHICS
Criteria for the diagnosis of preeclampsia
Systolic blood pressure 140 mmHg or diastolic blood pressure 90
mmHg on two occasions at least 4 hours apart after 20 weeks of
gestation in a
previously normotensive patient
If systolic blood pressure is 160 mmHg or diastolic blood
pressure is 110 mmHg, confirmation within minutes is sufficient
and
Proteinuria 0.3 grams in a 24-hour urine specimen or protein
(mg/dL)/creatinine (mg/dL) ratio 0.3
Dipstick 1+ if a quantitative measurement is unavailable
In patients with new onset hypertension without proteinuria, the
new onset of any of the following is diagnostic of
preeclampsia:
Platelet count 1.1 mg/dL or doubling of serum creatinine in the
absence of other renal disease
Liver transaminases at least twice the normal concentrations
Pulmonary edema
Cerebral or visual symptoms
Adapted from: Hypertension in pregnancy: Report of the American
College of Obstetricians and Gynecologists' Task Force on
Hypertension in Pregnancy. Obstet
Gynecol 2013; 122:1122.
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The presence of one or more of the following criteria are
features of severe preeclamptic disease
Symptoms of central nervous system dysfunction:
New onset cerebral or visual disturbance, such as:
Photopsia, scotomata, cortical blindness, retinal vasospasm
Severe headache (ie, incapacitating, "the worst headache I've
ever had") or headache that persists and progresses despite
analgesic therapy
Altered mental status
Hepatic abnormality:
Severe persistent right upper quadrant or epigastric pain
unresponsive to medication and not accounted for by an alternative
diagnosis or serum transaminase
concentration twice normal, or both
Severe blood pressure elevation:
Systolic blood pressure 160 mmHg or diastolic blood pressure 110
mmHg on two occasions at least four hours apart while the patient
is on bedrest (unless the
patient is on antihypertensive therapy)
Thrombocytopenia:
1.1 mg/dL or doubling of serum creatinine concentration in the
absence of other renal disease)
Pulmonary edema
In contrast to older criteria, the 2013 criteria do not include
proteinuria >5 grams/24 hours and fetal growth restriction as
features of severe
disease.
Adapted from: Hypertension in pregnancy: Report of the American
College of Obstetricians and Gynecologists' Task Force on
Hypertension in Pregnancy. Obstet
Gynecol 2013; 122:1122.
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Reported frequency of signs and symptoms of HELLP syndrome
Sign/symptom Frequency, percent
Proteinuria 86 to 100
Hypertension 82 to 88
Right upper quadrant/epigastrict pain 40 to 90
Nausea, vomiting 29 to 84
Headache 33 to 61
Visual changes 10 to 20
Jaundice 5
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Peripheral smear in microangiopathic hemolytic
anemia showing presence of schistocytes
Peripheral blood smear from a patient with a
microangiopathic
hemolytic anemia with marked red cell fragmentation. The
smear
shows multiple helmet cells (small black arrows), other
fragmented red
cells (large black arrow); microspherocytes are also seen
(blue
arrows). The platelet number is reduced; the large platelet in
the
center (red arrow) suggests that the thrombocytopenia is due
to
enhanced destruction.
Courtesy of Carola von Kapff, SH (ASCP).
Graphic 70851 Version 5.0
Normal peripheral blood smear
High power view of a normal peripheral blood smear. Several
platelets (black arrows) and a normal lymphocyte (blue arrow)
can
also be seen. The red cells are of relatively uniform size and
shape.
The diameter of the normal red cell should approximate that of
the
nucleus of the small lymphocyte; central pallor (red arrow)
should
equal one-third of its diameter.
Courtesy of Carola von Kapff, SH (ASCP).
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Comparison of frequency of signs, symptoms, and laboratory
findings in TTP, HUS, and HELLP
TTP HUS HELLP
Abdominal pain ++ ++ ++
Low ADAMST13 activity +/++ /+
Anemia ++ ++ +
Elevated lactic dehydrogenase ++ very high values ++ very high
values ++
Elevated transaminases /+ /+ ++
Fever +
Headache or visual disturbance ++ ++
Hypertension +/++ ++ ++
Jaundice +
Nausea and vomiting ++ ++ ++
Proteinuria + and hematuria ++ ++
Thrombocytopenia ++ ++ ++
von Willebrand factor ++ ++
TTP: thrombotic thrombocytopenic purpura; HUS: hemolytic uremic
syndrome; HELLP: hemolysis, elevated liver function tests, low
platelets; +: prevalence of
finding in affected patients.
Adapted from: Stella CL, Dacus J, Guzman E, et al. The
diagnostic dilemma of thrombotic thrombocytopenic purpura/hemolytic
uremic syndrome in the obstetric
triage and emergency department: lessons from 4 tertiary
hospitals. Am J Obstet Gynecol 2009; 200:381. Original Table 4.
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Clinical characteristics of liver diseases in pregnancy
PLTS: platelet count; PT: prothrombin time; AP: alkaline
phosphatase; GGT: gammaglutamyl
transpeptidase; WBC: white blood cell count; LDH: lactate
dehydrogenase; ALT: alanine
aminotransferase; AST: aspartate aminotransferase; PP: Post
partum.
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HELLP syndrome
Liver biopsy from a patient with HELLP syndrome. The zones
immediately adjacent to the portal triads show collections of
red blood
cells, without inflammation or necrosis of hepatocytes.
Courtesy of Caroline A Riely, MD.
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Liver infarction subcapsular hematoma HELLP syndrome on CT
scan
An axial CT scan through the upper abdomen (A) shows a large
subcapsular hematoma
compressing the liver (arrow). Image B shows a large and
irregular perfusion defect involving
the right lobe and part of the left lobe of the liver
(arrows).
CT: computed tomography; HELLP: H: hemolysis, EL: elevated liver
enzymes, LP: low platelets
counts.
Courtesy of Jonathan B Kruskal, MD, PhD.
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Liver infarction HELLP syndrome on CT scan
An axial CT scan through the upper abdomen shows multiple
perfusion defects
(arrowheads) in the posterior aspect of the right lobe of the
liver. A subcapsular
hematoma is present (arrow). The spleen is enlarged (dashed
arrow).
CT: computed tomography; HELLP: H: hemolysis, EL: elevated liver
enzymes, LP: low
platelets counts.
Courtesy of Jonathan B Kruskal, MD, PhD.
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Hepatic hematoma with rupture
Magnetic resonance image from a pregnant woman with hepatic
hematoma with rupture. This cut shows collected blood under
the
hepatic capsule running from the dome of the liver down along
the
right side, pushing the remaining normal parenchyma towards
the
midline.
Reproduced with permission from Barton, JR, Sibai, BM, Am J
Obstet Gynecol
1996; 174:1820.
Graphic 68521 Version 2.0
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Subcapsular liver hematoma on MR
These magnetic resonance (MR) images are from a patient with
HELLP
syndrome and a subcapsular liver hematoma. (A) The T2 weighted
image shows
a 9 mm hyperintense focus (arrow) that could represent a small
laceration or a
hepatic cyst. (B) The T1 weighted image shows an adjacent
subcapsular
hematoma (arrowhead) with both hyperintense and hypointense
components
reflecting a complex solid thrombus. The subcapsular hematoma
was estimated
as occupying less than 10 percent of the liver surface.
Graphic 86843 Version 1.0
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Disclosures: Baha M Sibai, MD Nothing to disclose. Charles J
Lockwood, MD Nothing to disclose. Keith D Lindor, MD Nothingto
disclose. Vanessa A Barss, MD Employee of UpToDate, Inc. Equity Ow
nership/Stock Options: Merck; Pfizer; Abbvie.
Contributor disclosures are review ed for conflicts of interest
by the editorial group. When found, these are addressed by
vettingthrough a multi-level review process, and through
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Appropriatelyreferenced content is required of all authors and must
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