HELLP syndrome (hemolysis, elevated liver

enzymes, and low platelets)

Author: Baha M Sibai, MD
Section Editors: Charles J Lockwood, MD, MHCM, Keith D Lindor, MD
Deputy Editor: Vanessa A Barss, MD, FACOG

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Feb 2024. | This topic last updated: Nov 27, 2023.

INTRODUCTION

HELLP is an acronym that refers to a syndrome in pregnant and postpartum

individuals characterized by hemolysis with a microangiopathic blood smear, elevated
liver enzymes, and a low platelet count. It probably represents a severe form of
preeclampsia ( table 1A-B), but the relationship between the two disorders remains
controversial. HELLP may be a separate disorder from preeclampsia because as many
as 15 to 20 percent of patients with HELLP do not have antecedent hypertension or
proteinuria [1-3].

Birth eventually leads to resolution of signs and symptoms of HELLP. Maternal

complications are primarily related to bleeding, which can include hepatic
hemorrhage. Neonatal complications are primarily related to the gestational age at
birth, which is commonly preterm.

This topic will focus on the clinical presentation, diagnosis, differential diagnosis, and
management of HELLP syndrome. Preeclampsia is reviewed in detail separately.
● (See "Preeclampsia: Clinical features and diagnosis".)
● (See "Preeclampsia: Antepartum management and timing of delivery".)
● (See "Preeclampsia with severe features: Delaying delivery in pregnancies remote
from term".)

PREVALENCE
Prevalence ranges from 0.1 of normotensive pregnancies to 1 percent of pregnant
people with preeclampsia without severe features, depending on the diagnostic
criteria used.

RISK FACTORS
● Previous history of HELLP. (See 'Recurrence in subsequent pregnancies' below.)
● Several genetic variants have been associated with an increased risk for HELLP in
research studies [4]. (See 'Pathogenesis' below.)

In contrast to preeclampsia, nulliparity is not a risk factor for HELLP [5]. Multiparous
individuals account for ≥50 percent of affected patients.

PATHOGENESIS

The pathogenesis of HELLP is unclear. If it is a severe form of preeclampsia, it likely

has the same origin (see "Preeclampsia: Pathogenesis"). If it is a separate entity, it can
still have a similar origin (eg, shallow placentation), but for unknown reasons it may
then diverge along a different pathway in which hepatic inflammation and activation
of the coagulation system exceeds that in preeclampsia [4,6,7].

A subset of HELLP may be related to thrombotic microangiopathy caused by

complement dysregulation (ie, complement-mediated thrombotic microangiopathy
[CM-TMA]), which may be treatable without prompt fetal delivery. In a case report of a
patient with severe early HELLP, treatment with eculizumab, a targeted inhibitor of
complement protein C5, was associated with marked clinical improvement and
complete normalization of laboratory parameters for 16 days, after which HELLP
recurred [8]. The authors chose this intervention based on the hypothesis that
preeclampsia with severe features/HELLP is a systemic inflammatory disorder
mediated by the complement cascade and the observation that pregnant individuals
with pathogenic variants in complement regulatory proteins appear to be at
increased risk for developing preeclampsia with severe features [9]. Further research
of possible benefits and harms is needed before such a clinical approach becomes
advisable [10].
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
[11,12]. In one case series, all six pregnancies with fetal LCHAD deficiency developed
severe maternal liver disease (HELLP or acute fatty liver of pregnancy [AFLP]) [13].
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 HELLP syndrome
during their pregnancies [14]. Although these findings inform theories about the
pathogenesis of HELLP, evaluation for genetic variants associated with LCHAD
deficiency has no role in clinical management of patients with HELLP. (See "Acute fatty
liver of pregnancy", section on 'Fetal long-chain 3-hydroxyacyl CoA dehydrogenase
(LCHAD) deficiency'.)

PATHOPHYSIOLOGY

Microangiopathy and activation of intravascular coagulation can account for all of the
laboratory findings in HELLP syndrome (see 'Laboratory criteria for diagnosis' below).
Hepatic histology may show microvascular fibrin deposition, neutrophilic infiltrate,
fatty infiltration, lobular necrosis, and periportal hemorrhage ( picture 1) [15].
Although kidney dysfunction is not an essential diagnostic criterion, microvascular
dysfunction may also occur in the kidney and may increase its vulnerability to an
ischemic insult [16].

PATIENT PRESENTATION

Signs and symptoms — HELLP has a variable presentation; the frequency of typical
signs and symptoms is shown in the table ( table 2) [17]. Symptoms typically present
over a short period of time and progressively worsen.

Most patients have upper abdominal pain, which is probably the most common
symptom. It may be localized to the midepigastrium, right upper quadrant, or below
the sternum and the area may be tender on physical examination [18]. The pain is
often severe and usually constant but may be fluctuating and colicky. Many patients
also have nausea, vomiting, and generalized malaise, which may be mistaken for a
nonspecific viral illness or viral hepatitis, particularly if the serum aspartate
aminotransferase (AST) and lactate dehydrogenase (LDH) levels are markedly
elevated. The median AST level was 249 (range 70 to 6200) and the median LDH level
was 853 units/L (range 560 to over 23,000) in one large series [18].

On physical examination, hypertension (defined as blood pressure ≥140/90 mmHg)

and proteinuria are present in approximately 85 percent of cases, but it is important
to note that either or both may be absent in patients with HELLP [17].

Thrombocytopenia-related bleeding (mucosal, hematuria, petechial hemorrhages,

ecchymosis) is an unusual presentation [17]. The median platelet count was 57,000
cells/microL (range 7000 to 99,000) in one large series [18].

Severe manifestations — Serious maternal morbidity may be present at initial

presentation or develop shortly thereafter.

Substantial hepatic bleeding (subcapsular or intraparenchymal liver hematoma) and

rupture may lead to very severe pain, hypotension and tachycardia; shoulder, chest,
back, or neck pain; dyspnea or pain on inspiration; nausea/vomiting; and/or
abdominal distention beyond that expected for the pregnant state [19-21]. In the
overall population of patients with HELLP, the incidence of subcapsular hematoma is
estimated to be 0.9 to 1.6 percent [18,22]. The aminotransferases in patients with
hepatic bleeding are usually modestly elevated, but values of 4000 to 6000
international units/L can occasionally be seen.

Some HELLP cases are complicated by eclampsia [18,23]. Other severe manifestations
include placental abruption, acute kidney injury, pulmonary edema, and retinal
detachment [18]. Disseminated intravascular coagulation (DIC), if present, is usually
associated with abruption, severe peripartum bleeding, or fulminant liver failure. (See
'Maternal outcome' below.)

Gestational age at onset — Symptoms typically develop between 28 and 37 weeks of

gestation, but onset in the late second trimester or at term/postpartum is also
common. In a series including over 440 pregnancies complicated by HELLP, 70 percent
of cases occurred before birth, approximately 80 percent of these occurred before <37
weeks, approximately 20 percent occurred before 28 weeks, and <3 percent occurred
at 17 to 20 weeks [18].

In the 30 percent of cases that occurred postpartum, most were diagnosed within 48
hours after birth, but occasionally as long as seven days; 80 percent had evidence of
preeclampsia before birth. Why some cases of HELLP and preeclampsia develop
postpartum is unknown and confusing since expulsion of the placenta initiates
resolution of the disease in most patients.

DIAGNOSTIC EVALUATION

In pregnant individuals with characteristic symptoms of HELLP (eg, right upper

quadrant/midepigastric pain, nausea, vomiting, malaise) and/or new-onset
hypertension in the second half of pregnancy or first postpartum week, we order the
laboratory tests needed to establish/exclude the diagnosis of HELLP. Because in rare
cases of preeclampsia severe persistent upper abdominal pain may precede
laboratory abnormalities by several hours, repeating the laboratory tests in four to six
hours may be helpful unless another cause for the pain has been determined [24].

Laboratory work-up includes [17]:

● Complete blood count
● Peripheral smear
● Aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin
● Creatinine

A lactate dehydrogenase (LDH) level (as a marker for hemolysis) is needed to make a
diagnosis of HELLP in some diagnostic protocols, thus it should be obtained at the
same time as the initial laboratory work-up or secondarily in patients with elevated
aminotransferases. In patients with elevated aminotransferases, the author of this
topic obtains haptoglobin and LDH levels and coagulation studies (fibrinogen,
prothrombin time, activated partial thromboplastin time). The coagulation studies are
obtained to rule out acute fatty liver of pregnancy (AFLP) in the absence of abruption
and severe thrombocytopenia.
DIAGNOSIS

The diagnosis of HELLP is based upon the presence of all of the laboratory
abnormalities comprising its name (hemolysis with a microangiopathic blood smear
[fragmented red blood cells; ie, schistocytes, burr cells], elevated liver enzymes, and
low platelet count) in a pregnant/postpartum patient.

Pregnant/postpartum patients who have some of the typical laboratory abnormalities

but do not have all of the laboratory criteria described below are considered to have
partial HELLP (eg, cases without hemolysis have been termed ELLP) [5]. These patients
may progress and eventually meet all laboratory criteria.

Laboratory criteria for diagnosis

Tennessee classification — The author of this topic requires the presence of all the
following criteria to diagnose HELLP (called Tennessee classification) [25]:
● Hemolysis, established by at least two of the following:

• Peripheral smear with schistocytes and burr cells ( picture 2).

• Serum bilirubin ≥1.2 mg/dL (20.52 micromol/L).
• Low serum haptoglobin (≤25 mg/dL) or lactate dehydrogenase (LDH) ≥2 times
the upper level of normal (based on laboratory-specific reference ranges).
• Severe anemia unrelated to blood loss. (Severe anemia in pregnancy can be
defined as hemoglobin level <8 to 10 g/dL, depending on the trimester). (See
"Anemia in pregnancy", section on 'Definition of anemia'.)
● Elevated liver enzymes:

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2 times

the upper level of normal (based on laboratory-specific reference ranges). (The
use of twice the upper limit of normal threshold was chosen, in part, to avoid
problems related to differences in assays, which may result in an elevated
absolute value in one hospital that is considered near normal in another).
● Low platelets: <100,000 cells/microL

In HELLP, an elevated LDH level is a nonspecific marker that can be associated with
severe hemolysis, acute hepatocellular injury, or both. The total bilirubin level is
increased as a result of an increase in the indirect (unconjugated) fraction from
hemolysis. Haptoglobin level is a specific marker of hemolysis: 25 mg/dL provides the
best cutoff between hemolytic and nonhemolytic disorders. (See "Diagnosis of
hemolytic anemia in adults", section on 'High LDH and bilirubin; low haptoglobin'.)

Other diagnostic criteria — The author prefers the Tennessee criteria because it
does not require LDH >600 international units/L, which is nonspecific and not present
in some patients who otherwise exhibit all features of HELLP.
● ACOG – The American College of Obstetricians and Gynecologists (ACOG)
suggests slightly different diagnostic criteria and acknowledges the absence of
clinical consensus among experts [26]. ACOG requires all of the following for
diagnosis of HELLP:

• LDH ≥600 international units/L

• AST and ALT elevated more than twice the upper limit of normal
• Platelet count <100,000 cells/microL
● Mississippi classification – Some clinicians use the Mississippi classification
system, which is based on severity of thrombocytopenia [27]:

• Class 1 – Platelet count ≤50,000 cells/microL plus LDH >600 international

units/L and AST or ALT ≥70 international units/L

• Class 2 – Platelet count >50,000 but ≤100,000 cells/microL plus LDH >600
international units/L and AST or ALT ≥70 international units/L

• Class 3 – Platelet count >100,000 but ≤150,000 cells/microL plus LDH >600
international units/L and AST or ALT ≥40 international units/L

DIFFERENTIAL DIAGNOSIS

Differential diagnosis is discussed in detail separately. (See "Hypertensive disorders in

pregnancy: Approach to differential diagnosis".)

A few key points: The four major disorders in differential diagnosis are acute fatty liver
of pregnancy (AFLP), thrombotic thrombocytopenic purpura (TTP), pregnancy-related
complement-mediated thrombotic microangiopathy (CM-TMA), and systemic lupus
erythematosus. Distinguishing features of HELLP and these other disorders are
shown in the tables ( table 3A-B). There is also overlap with preeclampsia with
severe features, which may not be a separate disease [28,29]. In HELLP, angiopathy
(including thrombotic microangiopathy and microangiopathic hemolytic anemia) and
liver dysfunction are marked, and the magnitude of hypertension is not highly
correlated with the level of angiopathy and liver dysfunction. By contrast, most cases
of severe preeclampsia have severe hypertension; thrombocytopenia and liver
dysfunction, although present, are not as markedly abnormal as in HELLP. However,
the clinical and histologic features are so similar that establishing the correct
diagnosis may not be possible; furthermore, HELLP can occur concurrently with these
disorders. Likewise, SARS-CoV-2 infection during pregnancy has been associated with
a significant increase in the odds of preeclampsia with severe features, eclampsia, and
HELLP [30]. The laboratory abnormalities of COVID-19 and HELLP can overlap, making
diagnosis of HELLP difficult in infected patients. (See "COVID-19: Overview of
pregnancy issues", section on 'Risk of preeclampsia'.)

MANAGEMENT

Our general approach is shown in the algorithm ( algorithm 1).

Site of care — Because of the potential for life-threatening maternal complications

(eg, liver rupture, acute kidney injury, disseminated intravascular coagulation [DIC]),
which can develop rapidly and necessitate preterm birth, patients with HELLP should
be managed at a tertiary care center with appropriate levels of maternal and neonatal
intensive care, when possible. (See 'Maternal outcome' below and 'Fetal/neonatal
outcome' below.)

The risk for serious morbidity correlates with increasing severity of maternal
symptoms and laboratory abnormalities [27,31]. In a report of four patients with
aspartate aminotransferase (AST) levels >2000 international units/L and lactate
dehydrogenase (LDH) levels >3000 international units/L, all had disordered mental
status, jaundice, intense hemolysis, and severe hypertension; one had multiorgan
failure; and two died [31].
Treatment of severe hypertension — Severe hypertension, if present, requires
prompt administration of one or more of the antihypertensive medications in this
table ( table 4) to reduce the risk of stroke. The approach to antihypertensive
therapy is the same as that for preeclampsia ( algorithm 2). (See "Treatment of
hypertension in pregnant and postpartum patients", section on 'Acute therapy of
severe hypertension'.)

In hemodynamically stable patients, intravenous fluids are administered

conservatively, as in patients with preeclampsia. (See "Preeclampsia: Intrapartum and
postpartum management and long-term prognosis", section on 'Fluids'.)

Hepatic imaging in patients with severe right upper quadrant/epigastric

pain — Because of the poor correlation between the magnitude of laboratory
abnormalities and liver histology [15], patients with severe symptoms (eg, persistent
severe midepigastric pain not responding to opioids, tenderness on liver palpation,
shoulder or neck pain, pain on inspiration) should undergo an appropriate imaging
study expeditiously to look for hepatic bleeding, even if liver enzymes are not
severalfold above the normal range, and to assess for other pathology [19,20,25].
Bedside ultrasound screening (focused assessment with sonography for trauma
[FAST]) is a good initial study, followed by formal ultrasound examination and
computed tomography (CT) or magnetic resonance imaging (MRI), when needed for
clinical decision making. Imaging using CT ( image 1 and image 2) or MRI
( image 3 and image 4) is more accurate than ultrasound for detecting a liver
hematoma and rupture but may not be as readily available and CT exposes the fetus
to ionizing radiation. This is not an issue with noncontrast MRI, which is felt to be safe
for the fetus. Issues regarding CT, MRI, and contrast in pregnant and lactating
patients are discussed in more detail separately. (See "Diagnostic imaging in pregnant
and lactating patients".)

Management of hepatic bleeding — Hepatic bleeding may remain contained or the

liver may rupture, resulting in hemorrhage into the peritoneal cavity. Rupture is a life-
threatening complication for both the mother and fetus, especially if diagnosis and
treatment are delayed.
● The patient should be supported with volume replacement and transfusion of
blood and blood products, as needed.

• We transfuse red blood cells if the hemoglobin is <7 g/dL and/or if the patient
has ecchymosis, severe hematuria, or suspected abruption.

• Actively bleeding patients with thrombocytopenia should be transfused with

platelets. Platelet transfusion may be indicated to prevent excessive bleeding
during birth 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. It is also useful to notify the blood bank
that platelet transfusions may be required.

If cesarean birth 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 [17], but the minimum count
before a neuraxial procedure is controversial and depends on factors in
addition to platelet concentration. (See "Platelet transfusion: Indications,
ordering, and associated risks", section on 'Preparation for an invasive
procedure' and "Adverse effects of neuraxial analgesia and anesthesia for
obstetrics", section on 'Neuraxial analgesia and low platelets'.)
● Prompt cesarean birth is indicated when the patient is hemodynamically stable
and severe anemia and coagulopathy, if present, have been corrected. We
stabilize the patient before the cesarean, even in cases with nonreassuring fetal
heart rate patterns or a low biophysical profile score. A team experienced in liver
trauma surgery should be consulted during maternal stabilization and prior to
delivery [32].

A hematoma that is unruptured and not expanding on initial imaging may be

managed conservatively. The appearance of the hematoma depends on the age
of the hematoma and the duration of and extension of the bleed. Subacute blood
on ultrasound is echogenic.

Repeat ultrasound evaluation of the liver is performed 48 hours after the delivery.
If liver findings remain stable, repeat imaging is performed again in one week
 and at six weeks postpartum. It may take months for a hematoma to resolve
completely [19,25]. Patients with resolving laboratory abnormalities may be
discharged home with outpatient follow-up.
● An expanding or ruptured hematoma requires operative management, which
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 has been successful in
case reports [33]. Liver transplantation because of massive spontaneous hepatic
rupture or acute liver failure has been life-saving in case reports [34-37].
● Similar considerations apply to postpartum patients with hepatic bleeding.
Surgical intervention is always required for those with hemodynamic instability
and generally required for those with persistent bleeding, increasing pain, or
continued expansion of the hematoma on serial ultrasound examinations [38];
however, percutaneous embolization of the hepatic arteries is a reasonable first-
line therapy in patients who are hemodynamically stable [39,40].

DIC, pulmonary edema, or acute kidney injury — Patients with disseminated

intravascular coagulation (DIC), pulmonary edema, or acute kidney injury should be
stabilized using standard therapies.
● (See "Disseminated intravascular coagulation (DIC) during pregnancy: Clinical
findings, etiology, and diagnosis" and "Disseminated intravascular coagulation
(DIC) during pregnancy: Management and prognosis".)
● (See "Acute respiratory failure during pregnancy and the peripartum period",
section on 'Pulmonary edema'.)
● (See "Acute kidney injury in pregnancy".)

Magnesium sulfate — Magnesium sulfate is initiated at the time of admission to the

labor and delivery unit and continued for 24 hours postpartum to prevent maternal
seizures. (See "Preeclampsia: Intrapartum and postpartum management and long-
term prognosis", section on 'Seizure prophylaxis'.)

It also provides fetal/neonatal neuroprotection when administered to pregnancies

<32 weeks of gestation. (See "Neuroprotective effects of in utero exposure to
magnesium sulfate".)

Role of therapeutic plasma exchange — Therapeutic plasma exchange has no

benefit in patients with HELLP, but is the mainstay of treatment for patients with
thrombotic thrombocytopenic purpura (TTP). Because patients with HELLP and those
with TTP have both microangiopathic hemolysis and thrombocytopenia, making the
correct diagnosis and, in turn, initiating the appropriate treatment can be challenging.
Differential diagnosis is discussed in more detail separately. (See "Hypertensive
disorders in pregnancy: Approach to differential diagnosis", section on 'Thrombotic
microangiopathy: TTP and HUS'.)

Delivery timing

Prompt delivery (preferred approach for most patients) — Delivery is the

cornerstone of therapy for HELLP and is the only effective treatment. After maternal
stabilization, the consensus among experts is that prompt delivery is indicated for
pregnancies ≥34 weeks of gestation and pregnancies <34 weeks with severe
complications (eg, abruption, hepatic bleeding, DIC, acute kidney injury,
nonreassuring fetal status, pulmonary edema, fetal death, seizure, stroke) [17,41]. In
pregnancies <34 weeks without severe complications, delivery can be delayed for 48
hours for antenatal corticosteroid administration (see 'Delayed delivery for up to 48
hours in selected pregnancies <34 weeks' below). However, pregnancies that have not
reached a stage of fetal maturity that ensures a reasonable chance of extrauterine
survival after a course of steroids are delivered promptly since expectant
management is associated with a high risk of developing maternal complications
without significant improvement in perinatal prognosis. (See 'Maternal outcome'
below and 'Fetal/neonatal outcome' below.)

We do not manage patients with HELLP syndrome expectantly at any gestational age
and consider delaying delivery 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 antenatal
corticosteroids and no maternal benefits from expectant management. The following
studies support our approach:
● In a study that treated 128 patients with HELLP <34 weeks of gestation with
volume expansion and pharmacologic vasodilation under invasive hemodynamic
monitoring, delivery was necessitated in 22 out of 128 (17 percent) of patients
within 48 hours; the remaining patients had a median prolongation of pregnancy
of 15 days [42]. Although there was no maternal mortality or serious maternal
morbidity and more than one-half (55 out of 102) of the patients had complete
reversal of their laboratory abnormalities with expectant management, 11 fetal
and 7 neonatal deaths occurred.
● In another series, 41 patients with HELLP <35 weeks of gestation were managed
expectantly [43]. Delivery was required within 48 hours in 14 out of 41 (34
percent), the remaining patients had a median prolongation of pregnancy of
three days, and more than one-half (15 out of 27) had compete reversal of their
laboratory abnormalities [43]. However, there were 10 fetal deaths.

Delayed delivery for up to 48 hours in selected pregnancies <34

weeks — Delaying delivery for up to 48 hours for administration of a course of
antenatal corticosteroids can improve neonatal outcome in pregnancies <34 weeks
that have reached a stage of fetal maturity that ensures a reasonable chance of
extrauterine survival, but this benefit must be balanced against the maternal risk of
developing complications in an ongoing pregnancy [17,41]. Although a short delay in
delivery for betamethasone administration does not appear to increase maternal or
fetal morbidity or mortality [44], we advise not attempting to delay delivery beyond 48
hours because disease progression usually occurs, sometimes with rapid maternal
deterioration. Evidence of the efficacy of antenatal corticosteroids is reviewed
separately. (See "Antenatal corticosteroid therapy for reduction of neonatal
respiratory morbidity and mortality from preterm delivery", section on 'Evidence of
efficacy'.)
We do not give betamethasone for fetal lung maturity in pregnancies with gestational
age ≥34 weeks since no patients with HELLP were enrolled in randomized trials of the
efficacy of steroids after 34 weeks. Furthermore, the marginal fetal benefit of steroids
beyond 34 weeks is likely less than the maternal risk of expectant management.
During administration of betamethasone, all patients are kept in the labor and
delivery unit with continuous fetal monitoring. (See "Antenatal corticosteroid therapy
for reduction of neonatal respiratory morbidity and mortality from preterm delivery",
section on 'Long-term harms'.)

The author of this topic repeats the complete blood count (including platelet count) at
24 and 48 hours after administering steroids and more often if clinical deterioration is
suspected. The American College of Obstetricians and Gynecologists (ACOG)
recommends laboratory testing at least at 12-hour intervals until birth and in the
postpartum period [26]. This information is useful when considering whether to
administer red blood cell transfusions, whether neuraxial anesthesia can be
performed safely (see "Adverse effects of neuraxial analgesia and anesthesia for
obstetrics", section on 'Neuraxial analgesia and low platelets'), and whether platelet
transfusion is indicated (See 'Management of hepatic bleeding' above.).

Choosing the route of birth — Vaginal birth is desirable in the absence of standard
indications for cesarean birth (eg, breech, nonreassuring fetal status) and hepatic
bleeding.

We induce patients with HELLP uncomplicated by hepatic bleeding regardless of

gestational age when the cervix is favorable. When the cervix is unfavorable, we
believe cesarean birth is probably preferable to induction in pregnancies less than 30
to 32 weeks of gestation, especially if signs of fetal compromise (growth restriction,
oligohydramnios) are present. 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 [17]. (See "Induction of labor with oxytocin" and
"Induction of labor: Techniques for preinduction cervical ripening".)

In patients with HELLP complicated by hepatic bleeding, we suggest cesarean birth

because the increased intrabdominal pressure during vomiting and pushing can lead
to further hepatic bleeding, even in patients who have undergone embolization by
interventional radiology. Performing cesarean avoids this and allows visual evaluation
of the source and amount of bleeding. Although the consequences of vaginal birth in
patients with liver hematoma has not been studied, cesarean birth has been
recommended for patients with esophageal varices as most cases of maternal
mortality due to variceal hemorrhage occurred during vaginal birth [45].

Anesthesia/analgesia — Thrombocytopenia and coagulation abnormalities may

preclude use of neuraxial anesthesia for labor and birth. The minimum platelet count
necessary to safely perform neuraxial anesthesia is unknown, and practice varies. Use
of neuraxial and general anesthesia for these patients is reviewed separately. (See
"Anesthesia for the patient with preeclampsia", section on 'Coagulation'.)

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".)

Performing cesarean birth and exploring the abdomen — Management of

thrombocytopenia at delivery is the same as in patients with thrombocytopenia
related to preeclampsia with severe features, and reviewed separately. (See
"Preeclampsia: Intrapartum and postpartum management and long-term prognosis",
section on 'Management of thrombocytopenia'.)

If preoperative imaging was not performed in a patient with findings suggestive of

liver hematoma, we perform a midline skin incision and very gently palpate the liver
to assess for the presence of an unruptured hematoma, after extracting the fetus and
placenta.

Because of the increased risk of subfascial and wound hematoma in patients with
thrombocytopenia who undergo cesarean birth, the author of this topic places a
subfascial drain and leaves the skin incision open for the first 48 postoperative hours
[3]. Some surgeons place a subfascial and/or suprafascial drain and close the incision
with staples, so it is easy to open partially if a hematoma develops. The management
of the abdominal wall incision after cesarean should be individualized, depending on
the surgeon's assessment of risk of hematoma/seroma development.

Is there a role for dexamethasone in treatment of HELLP? — We do not treat

patients with HELLP syndrome with dexamethasone. The two largest, randomized,
double-blind, placebo-controlled trials evaluating the use of dexamethasone to
improve maternal outcome in patients with HELLP syndrome did not establish a
benefit [46,47], in contrast to initial observational studies and small randomized trials
that suggested more rapid improvement in maternal laboratory and clinical
parameters [48-51].

In a meta-analysis of 11 trials (550 participants) comparing corticosteroid treatment

with placebo/no treatment in HELLP, steroid administration did not lead to a
convincing reduction in maternal death (risk ratio [RR] 0.95, 95% CI 0.28-3.21),
maternal death or severe maternal morbidity (RR 0.27, 95% CI 0.03-2.12), or
perinatal/infant death (RR 0.64, 95% CI 0.21-1.97), but the standardized mean
difference in platelet count favored the steroid group (0.67, 95% CI 0.26-1.10) [52]. A
subsequent randomized trial with an additional 132 patients assigned to
dexamethasone or placebo reported no significant differences in the time to recovery
of platelet counts and aspartate aminotransferase levels or frequency of
complications [46].

The use of dexamethasone rather than betamethasone to promote fetal pulmonary

maturity is a separate issue. (See "Antenatal corticosteroid therapy for reduction of
neonatal respiratory morbidity and mortality from preterm delivery", section on
'Betamethasone or dexamethasone?'.)

POSTPARTUM

All of the signs and symptoms of HELLP, including subcapsular hematoma and liver
rupture, can initially appear in the postpartum period [53]. Management is similar to
that of HELLP diagnosed before birth, except fetal status no longer needs to be
considered.
Maternal care — Patients who are critically ill or at substantial risk for developing
serious complications can benefit from transfer to an intensive care setting, rather
than a postpartum unit. Potential indications for intensive monitoring include
threatened or actual liver rupture or fulminant liver failure, disseminated
intravascular coagulation (DIC), acute kidney injury, massive transfusion, transfusion-
related acute lung injury, and cardiac ischemia or cardiomyopathy.

Supportive care may involve oxygenation and ventilation (ie, supplemental oxygen or
mechanical ventilation), sedation, pain control, hemodynamic support (ie,
vasopressors), intensive monitoring, volume management (ie, intravenous fluids or
diuretics), nutritional support, stress ulcer prophylaxis, and venous thromboembolism
prophylaxis. (See "Critical illness during pregnancy and the peripartum period".)

Laboratory monitoring — Laboratory results may initially worsen in the 48 hours

following birth (eg, platelet count usually decreases by 40 percent/day, hematocrit
falls, and liver enzymes increase) [54], which is the reason that the American College
of Obstetricians and Gynecologists (ACOG) recommends laboratory testing at least at
12-hour intervals in the postpartum period [26]. We stop checking laboratory values
once they are clearly beginning to stabilize. In the absence of bleeding or
complications related to HELLP, there is no benefit for further serial evaluation of
platelet counts or liver enzymes. Although liver enzymes return to normal or
substantially decrease by the fourth postpartum day [46,47,54,55], in one report, total
bilirubin levels were elevated in 20 percent of patients who had liver function tests
checked 3 to 101 months after giving birth [56].

An upward trend in platelet count and a downward trend in lactate dehydrogenase

(LDH) concentration are usually seen by the fourth postpartum day in the absence of
complications. In a series of 158 patients with HELLP syndrome, platelet counts
decreased until 24 to 48 hours after birth, while serum LDH concentration usually
peaked at this time [54]. In all patients who recovered, a platelet count greater than
100,000 cells/microL was achieved by the sixth postpartum day or within 72 hours of
the platelet nadir. Others have reported similar findings [55]. The platelet count
rebound can overshoot; one group reported values of 413,000 to 871,000 cells/microL
[57].
 If the platelet count continues to fall and LDH continues to rise after the fourth
postpartum day, then diagnoses other than HELLP syndrome (eg, primary
thrombotic microangiopathy) should be considered [26]. However, recovery can
be delayed in patients with particularly severe HELLP, such as those with DIC,
platelet count less than 20,000 cells/microL, renal dysfunction, or ascites [17,58].
These patients are at risk of developing pulmonary edema and acute kidney
injury.

OUTCOME AND PROGNOSIS

Maternal outcome — The outcome for patients with HELLP is generally good;
however, serious complications are relatively common. In the author's series of 437
patients with HELLP syndrome at a tertiary care facility, the following complications
were observed [18]. Many complications are interdependent (eg, abruption is a
common obstetric etiology of DIC, which, in turn, may induce acute kidney injury,
which may lead to pulmonary edema; massive bleeding from the liver, postpartum
uterine atony, or lacerations could also lead to DIC).
● Bleeding – 55 percent required transfusions with blood or blood products; 2
percent required laparotomies for major intraabdominal bleeding
● Disseminated intravascular coagulation (DIC) – 21 percent
● Placental abruption – 16 percent
● Acute kidney injury – 8 percent
● Pulmonary edema – 6 percent
● Subcapsular liver hematoma (or hepatic rupture) – 1 percent
● Retinal detachment – 1 percent
● Intracerebral hemorrhage – <1 percent
● Death – 1 percent

Serious maternal complications were observed in 25 of 56 cases (45 percent) of early-

onset HELLP syndrome (<23 weeks) in a systematic review [59]. The most common
were hepatic (13 in 56 [23 percent]), central-nervous-system-related (11 in 56 [20
percent]), respiratory (11 in 56 [20 percent]), acute kidney injury (4 of 56 [7 percent]),
and DIC (3 of 56 [5 percent]), with one maternal death. A systematic review of
pregnant patients with spontaneous liver hematomas reported maternal mortality in
15 percent of cases [60].

Additional complications that have been reported in other series include adult
respiratory distress syndrome, sepsis, stroke, cerebral hemorrhage and edema, and
hepatic infarction (in patients with antiphospholipid syndrome, which has been
diagnosed in nearly 50 percent of early-onset cases [59]) [5,61,62]. Wound
complications secondary to bleeding and hematomas are common in patients with
thrombocytopenia.

HELLP with or without acute kidney injury does not affect long-term kidney function
[63,64]. Similarly, there are no ongoing hepatic sequelae following recovery from
hepatic bleeding with/without rupture.

Fetal/neonatal outcome — The neonatal and long-term prognoses are most

strongly associated with gestational age at birth and birth weight [65-73]. Preterm
birth is common (70 percent; with 15 percent of births before 27 weeks) [65].
Leukopenia, neutropenia, and thrombocytopenia may be observed in the neonate but
appear to be related to fetal growth restriction, preterm birth, and maternal
hypertension rather than HELLP [67]. Maternal HELLP does not affect fetal/neonatal
liver function.

The overall perinatal mortality rate is 7 to 20 percent; complications of preterm birth,

fetal growth restriction, and abruption are the leading causes of perinatal death
[17,66]. The severity of hemolysis, liver disfunction, and thrombocytopenia does not
correlate with the risk of fetal demise, except in cases of liver hematoma or rupture
where fetal mortality was 40 percent in a systematic review [60].

Early-onset HELLP syndrome has a very poor prognosis. In a systematic review

including 57 pregnancies with HELLP syndrome before 23 weeks of gestation and
known outcome, 36 (63 percent) were terminated and of the 21 continued
pregnancies, there were 10 fetal demises before 20 weeks, six stillbirths, two neonatal
deaths, and three living neonates (all born at 23 weeks) [59].

Recurrence in subsequent pregnancies — The risk of recurrent HELLP was about 4

percent for patients who were normotensive before onset of the syndrome, in a long-
term study of 139 patients with subsequent pregnancies [74]. However, these patients
were at increased risk for other placenta-mediated obstetric complications. In a meta-
analysis of individual patient data from 512 patients with HELLP who became
pregnant again, 7 percent developed HELLP, 18 percent developed preeclampsia, and
18 percent developed gestational hypertension in a subsequent pregnancy [75].

In a subsequent Norwegian registry-based study of 577 patients with HELLP in their

first pregnancy and then a second pregnancy, 24 percent developed hypertensive
disorders of pregnancy that included either HELLP syndrome, preeclampsia,
pregnancy-induced hypertension, or eclampsia in the second pregnancy compared
with 3.6 percent of patients with no HELLP in their first pregnancy [76]. The study did
not provide results for recurrent HELLP syndrome alone. The risk of recurrence of
hypertensive disorders of pregnancy was higher in patients with preterm versus term
HELLP in the first pregnancy (30.3 versus 16.5 percent).

Prevention — There is no evidence that any therapy prevents recurrent HELLP

syndrome, but data are limited. The author considers HELLP syndrome a form of
severe preeclampsia and prescribes low-dose aspirin during the second and third
trimesters in future pregnancies to reduce the risk of preeclampsia. Evidence for use
of low-dose aspirin for prevention of preeclampsia is discussed separately. (See
"Preeclampsia: Prevention", section on 'Low-dose aspirin'.)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links:
Hypertensive disorders of pregnancy".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond
the Basics." The Basics patient education pieces are written in plain language, at the
5th to 6th grade reading level, and they answer the four or five key questions a patient
might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10th to 12th grade reading level and are best for patients
who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage
you to print or e-mail these topics to your patients. (You can also locate patient
education articles on a variety of subjects by searching on "patient info" and the
keyword(s) of interest.)
● Basics topic (see "Patient education: HELLP syndrome (The Basics)" and "Patient
education: High blood pressure and pregnancy (The Basics)")

SUMMARY AND RECOMMENDATIONS

● Clinical presentation – The most common clinical presentation of HELLP
syndrome (hemolysis with a microangiopathic blood smear, elevated liver
enzymes, and low platelet count) is abdominal pain and tenderness in the
midepigastrium, right upper quadrant, or below the sternum ( table 2). Most
cases are diagnosed between 28 and 36 weeks of gestation, but signs/symptoms
may present up to seven days postpartum. (See 'Patient presentation' above.)
● Diagnosis – The diagnosis of HELLP is based on the presence of all of the
following criteria (Tennessee classification) (see 'Diagnosis' above):

• Hemolysis, established by at least two of the following:

- Peripheral smear with schistocytes and burr cells ( picture 2)
- Serum bilirubin ≥1.2 mg/dL (20.52 micromol)
- Low serum haptoglobin or lactate dehydrogenase (LDH) ≥2 times the upper
level of normal (based on laboratory-specific reference ranges)
- Severe anemia, unrelated to blood loss
• Elevated liver enzymes:
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2
times the upper level of normal (based on laboratory-specific reference
ranges)
 • Low platelets: <100,000 cells/microL
● Differential diagnosis – The four major disorders in differential diagnosis are
acute fatty liver of pregnancy (AFLP), thrombotic thrombocytopenic purpura
(TTP), pregnancy-related hemolytic-uremic syndrome, and systemic lupus
erythematosus. All have features that overlap with HELLP ( table 3A-B). (See
'Differential diagnosis' above.)
● Management – Because of the potential for life-threatening maternal
complications, which can develop rapidly and necessitate preterm birth, patients
with HELLP should be managed at a tertiary care center with appropriate levels of
maternal and neonatal intensive care. Our general approach to management is
shown in the algorithm ( algorithm 1). (See 'Management' above.)

• Severe hypertension – Severe hypertension, if present, requires prompt

administration of one or more of the antihypertensive medications in this table
( table 4) to reduce the risk of stroke. The approach to antihypertensive
therapy is the same as that for preeclampsia ( algorithm 2). This approach
and supporting evidence is available separately. (See "Treatment of
hypertension in pregnant and postpartum patients", section on 'Acute therapy
of severe hypertension'.)

• Hepatic imaging and management of hepatic bleeding – Patients with

severe right upper quadrant/epigastric pain should undergo hepatic imaging
as the pain may be due to hepatic bleeding, which may remain contained or
rupture the liver capsule. Management of hepatic bleeding involves volume
replacement and transfusion of blood and blood products, as needed. Prompt
cesarean birth is indicated once the patient is hemodynamically stable and
severe anemia and coagulopathy, if present, have been corrected.

A hematoma that is unruptured and not expanding may be managed

conservatively. An expanding or ruptured hematoma requires operative
management, which includes packing, drainage, hepatic artery ligation, and/or
resection of affected areas of the liver. A team experienced in liver trauma
surgery should be consulted during maternal stabilization and prior to
 delivery. (See 'Hepatic imaging in patients with severe right upper
quadrant/epigastric pain' above.)

• Magnesium sulfate – Magnesium sulfate is initiated at the time of admission

to the labor and delivery unit and continued for 24 to 48 hours postpartum to
prevent maternal seizures. It also provides fetal/neonatal neuroprotection. The
use of magnesium sulfate for these indications and evidence of efficacy of
magnesium sulfate are available separately. (See "Preeclampsia: Intrapartum
and postpartum management and long-term prognosis", section on 'Seizure
prophylaxis' and "Neuroprotective effects of in utero exposure to magnesium
sulfate".)
● Timing of delivery

• Pregnancies with serious complications – Pregnancies with serious maternal

or fetal complications (eg, abruption, hepatic bleeding, disseminated
intravascular coagulation [DIC], acute kidney injury, nonreassuring fetal status,
pulmonary edema) require prompt delivery regardless of gestational age. (See
'Prompt delivery (preferred approach for most patients)' above.)

• Pregnancies ≥34 weeks without serious complication – For pregnancies ≥34

weeks of gestation without serious maternal or fetal complications, we suggest
prompt delivery rather expectant management (Grade 2C). In this population,
the potential risks of preterm birth or iatrogenic term birth are outweighed by
the risk of developing serious complications associated with HELLP syndrome.
(See 'Prompt delivery (preferred approach for most patients)' above.)

• Pregnancies <34 weeks without serious complications

- For pregnancies <34 weeks without serious maternal or fetal complications
and at a stage of fetal maturity that ensures a reasonable chance of
extrauterine survival, we suggest delaying delivery for 48 hours for
administration of a course of antenatal corticosteroids rather than prompt
delivery (Grade 2C). (See 'Delayed delivery for up to 48 hours in selected
pregnancies <34 weeks' above and 'Prompt delivery (preferred approach for
most patients)' above.)
 - For preterm pregnancies that have not reached a stage of fetal maturity
that ensures a reasonable chance of extrauterine survival, we suggest
prompt delivery (Grade 2C). Expectant management is associated with a
high risk of developing maternal complications without significant
improvement in perinatal prognosis. (See 'Prompt delivery (preferred
approach for most patients)' above.)

• Route of birth – Vaginal birth is desirable in the absence of standard

indications for cesarean birth and hepatic bleeding (see 'Choosing the route of
birth' above and 'Performing cesarean birth and exploring the abdomen'
above). However:
- For pregnancies less than 30 to 32 weeks with an unfavorable cervix, we
suggest cesarean birth (Grade 2C). These patients are likely to have a
prolonged induction if vaginal birth is attempted.
- For patients with hepatic bleeding, we suggest cesarean birth (Grade 2C).
The intrabdominal pressure during vomiting and pushing can lead to
further hepatic bleeding.

Management of thrombocytopenia at delivery is the same as in patients with

thrombocytopenia related to preeclampsia with severe features, and reviewed
separately. (See "Preeclampsia: Intrapartum and postpartum management and
long-term prognosis", section on 'Management of thrombocytopenia'.)
● Postpartum course – Most patients have an upward trend in platelet count and a
downward trend in lactate dehydrogenase concentration by the fourth
postpartum day. We stop checking laboratory values once the patient is clearly
beginning to stabilize. (See 'Postpartum' above.)
● Outcome/prognosis

• Maternal – The outcome for mothers with HELLP syndrome is generally good,
but serious complications such as abruption, acute kidney injury, subcapsular
liver hematoma or hepatic rupture, pulmonary edema, hemorrhage, retinal
detachment, and death may occur. (See 'Maternal outcome' above.)
 Future pregnancies are at increased risk for developing HELLP, preeclampsia,
and gestational hypertension. (See 'Recurrence in subsequent pregnancies'
above.)

• Pediatric – The short-term and long-term pediatric prognoses are primarily

related to the gestational age at delivery and birth weight. Maternal HELLP
does not affect fetal/neonatal liver function. (See 'Fetal/neonatal outcome'
above.)
REFERENCES

1. Sibai BM, Taslimi MM, el-Nazer A, et al. Maternal-perinatal outcome associated

with the syndrome of hemolysis, elevated liver enzymes, and low platelets in
severe preeclampsia-eclampsia. Am J Obstet Gynecol 1986; 155:501.
2. Reubinoff BE, Schenker JG. HELLP syndrome--a syndrome of hemolysis, elevated
liver enzymes and low platelet count--complicating preeclampsia-eclampsia. Int J
Gynaecol Obstet 1991; 36:95.
3. Sibai BM. The HELLP syndrome (hemolysis, elevated liver enzymes, and low
platelets): much ado about nothing? Am J Obstet Gynecol 1990; 162:311.
4. Abildgaard U, Heimdal K. Pathogenesis of the syndrome of hemolysis, elevated
liver enzymes, and low platelet count (HELLP): a review. Eur J Obstet Gynecol
Reprod Biol 2013; 166:117.
5. Audibert F, Friedman SA, Frangieh AY, Sibai BM. Clinical utility of strict diagnostic
criteria for the HELLP (hemolysis, elevated liver enzymes, and low platelets)
syndrome. Am J Obstet Gynecol 1996; 175:460.
6. Benedetto C, Marozio L, Tancredi A, et al. Biochemistry of HELLP syndrome. Adv
Clin Chem 2011; 53:85.
7. Jebbink J, Wolters A, Fernando F, et al. Molecular genetics of preeclampsia and
HELLP syndrome - a review. Biochim Biophys Acta 2012; 1822:1960.
8. Burwick RM, Feinberg BB. Eculizumab for the treatment of preeclampsia/HELLP
syndrome. Placenta 2013; 34:201.
9. Salmon JE, Heuser C, Triebwasser M, et al. Mutations in complement regulatory
proteins predispose to preeclampsia: a genetic analysis of the PROMISSE cohort.
 PLoS Med 2011; 8:e1001013.
10. Burwick RM, Burwick NR, Feinberg BB. Eculizumab fails to inhibit generation of
C5a in vivo. Blood 2014; 124:3502.
11. Yang Z, Yamada J, Zhao Y, et al. Prospective screening for pediatric mitochondrial
trifunctional protein defects in pregnancies complicated by liver disease. JAMA
2002; 288:2163.
12. Yang Z, Zhao Y, Bennett MJ, et al. Fetal genotypes and pregnancy outcomes in 35
families with mitochondrial trifunctional protein mutations. Am J Obstet Gynecol
2002; 187:715.
13. Wilcken B, Leung KC, Hammond J, et al. Pregnancy and fetal long-chain 3-
hydroxyacyl coenzyme A dehydrogenase deficiency. Lancet 1993; 341:407.
14. Ibdah JA, Bennett MJ, Rinaldo P, et al. A fetal fatty-acid oxidation disorder as a
cause of liver disease in pregnant women. N Engl J Med 1999; 340:1723.
15. Barton JR, Riely CA, Adamec TA, et al. Hepatic histopathologic condition does not
correlate with laboratory abnormalities in HELLP syndrome (hemolysis, elevated
liver enzymes, and low platelet count). Am J Obstet Gynecol 1992; 167:1538.
16. Ye W, Shu H, Yu Y, et al. Acute kidney injury in patients with HELLP syndrome. Int
Urol Nephrol 2019; 51:1199.
17. Sibai BM. Diagnosis, controversies, and management of the syndrome of
hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol 2004;
103:981.
18. Sibai BM, Ramadan MK, Usta I, et al. Maternal morbidity and mortality in 442
pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP
syndrome). Am J Obstet Gynecol 1993; 169:1000.
19. Barton JR, Sibai BM. Hepatic imaging in HELLP syndrome (hemolysis, elevated liver
enzymes, and low platelet count). Am J Obstet Gynecol 1996; 174:1820.
20. Nunes JO, Turner MA, Fulcher AS. Abdominal imaging features of HELLP
syndrome: a 10-year retrospective review. AJR Am J Roentgenol 2005; 185:1205.
21. Brito M, Gamito M, Neves AR, et al. Conservative management of a pregnancy
complicated by preeclampsia and postpartum spontaneous hepatic rupture: A
 case report and review of the literature. Eur J Obstet Gynecol Reprod Biol 2021;
267:79.
22. Haddad B, Barton JR, Livingston JC, et al. Risk factors for adverse maternal
outcomes among women with HELLP (hemolysis, elevated liver enzymes, and low
platelet count) syndrome. Am J Obstet Gynecol 2000; 183:444.
23. Vigil-De Gracia P, Rojas-Suarez J, Ramos E, et al. Incidence of eclampsia with HELLP
syndrome and associated mortality in Latin America. Int J Gynaecol Obstet 2015;
129:219.
24. O'Brien JM, Barton JR. Controversies with the diagnosis and management of
HELLP syndrome. Clin Obstet Gynecol 2005; 48:460.
25. Ditisheim A, Sibai BM. Diagnosis and Management of HELLP Syndrome
Complicated by Liver Hematoma. Clin Obstet Gynecol 2017; 60:190.
26. Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222.
Obstet Gynecol 2020; 135:e237. Reaffirmed 2023.
27. Martin JN Jr, Rose CH, Briery CM. Understanding and managing HELLP syndrome:
the integral role of aggressive glucocorticoids for mother and child. Am J Obstet
Gynecol 2006; 195:914.
28. Lisonkova S, Bone JN, Muraca GM, et al. Incidence and risk factors for severe
preeclampsia, hemolysis, elevated liver enzymes, and low platelet count
syndrome, and eclampsia at preterm and term gestation: a population-based
study. Am J Obstet Gynecol 2021; 225:538.e1.
29. Haram K, Svendsen E, Abildgaard U. The HELLP syndrome: clinical issues and
management. A Review. BMC Pregnancy Childbirth 2009; 9:8.
30. Conde-Agudelo A, Romero R. SARS-CoV-2 infection during pregnancy and risk of
preeclampsia: a systematic review and meta-analysis. Am J Obstet Gynecol 2022;
226:68.
31. Catanzarite VA, Steinberg SM, Mosley CA, et al. Severe preeclampsia with
fulminant and extreme elevation of aspartate aminotransferase and lactate
dehydrogenase levels: high risk for maternal death. Am J Perinatol 1995; 12:310.
32. Stevenson JT, Graham DJ. Hepatic hemorrhage and the HELLP syndrome: a
surgeon's perspective. Am Surg 1995; 61:756.
33. Merchant SH, Mathew P, Vanderjagt TJ, et al. Recombinant factor VIIa in
management of spontaneous subcapsular liver hematoma associated with
pregnancy. Obstet Gynecol 2004; 103:1055.
34. Erhard J, Lange R, Niebel W, et al. Acute liver necrosis in the HELLP syndrome:
successful outcome after orthotopic liver transplantation. A case report. Transpl
Int 1993; 6:179.
35. 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.
36. 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.
37. Zarrinpar A, Farmer DG, Ghobrial RM, et al. Liver transplantation for HELLP
syndrome. Am Surg 2007; 73:1013.
38. Wilson RH, Marshall BM. Postpartum rupture of a subcapsular hematoma of the
liver. Acta Obstet Gynecol Scand 1992; 71:394.
39. Rinehart BK, Terrone DA, Magann EF, et al. Preeclampsia-associated hepatic
hemorrhage and rupture: mode of management related to maternal and
perinatal outcome. Obstet Gynecol Surv 1999; 54:196.
40. Grand'Maison S, Sauvé N, Weber F, et al. Hepatic rupture in hemolysis, elevated
liver enzymes, low platelets syndrome. Obstet Gynecol 2012; 119:617.
41. American College of Obstetricians and Gynecologists, Task Force on Hypertension
in Pregnancy. Hypertension in pregnancy. Report of the American College of
Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet
Gynecol 2013; 122:1122.
42. Visser W, Wallenburg HC. Temporising management of severe pre-eclampsia with
and without the HELLP syndrome. Br J Obstet Gynaecol 1995; 102:111.
43. van Pampus MG, Wolf H, Westenberg SM, et al. Maternal and perinatal outcome
after expectant management of the HELLP syndrome compared with pre-
 eclampsia without HELLP syndrome. Eur J Obstet Gynecol Reprod Biol 1998; 76:31.
44. Fitzpatrick KE, Hinshaw K, Kurinczuk JJ, Knight M. Risk factors, management, and
outcomes of hemolysis, elevated liver enzymes, and low platelets syndrome and
elevated liver enzymes, low platelets syndrome. Obstet Gynecol 2014; 123:618.
45. Rasheed SM, Abdel Monem AM, Abd Ellah AH, Abdel Fattah MS. Prognosis and
determinants of pregnancy outcome among patients with post-hepatitis liver
cirrhosis. Int J Gynaecol Obstet 2013; 121:247.
46. Fonseca JE, Méndez F, Cataño 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.
47. 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.
48. 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.
49. Matchaba P, Moodley J. Corticosteroids for HELLP syndrome in pregnancy.
Cochrane Database Syst Rev 2004; :CD002076.
50. Isler CM, Barrilleaux PS, Magann EF, et al. A prospective, randomized trial
comparing the efficacy of dexamethasone and betamethasone for the treatment
of antepartum HELLP (hemolysis, elevated liver enzymes, and low platelet count)
syndrome. Am J Obstet Gynecol 2001; 184:1332.
51. 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.
52. Woudstra DM, Chandra S, Hofmeyr GJ, Dowswell T. Corticosteroids for HELLP
(hemolysis, elevated liver enzymes, low platelets) syndrome in pregnancy.
Cochrane Database Syst Rev 2010; :CD008148.
53. Gilboa Y, Bardin R, Feldberg D, Bachar GN. Postpartum hepatic rupture and
retroperitoneal hematoma associated with HELLP syndrome. Isr Med Assoc J 2006;
8:219.
54. Martin JN Jr, Blake PG, Perry KG Jr, et al. The natural history of HELLP syndrome:
patterns of disease progression and regression. Am J Obstet Gynecol 1991;
164:1500.
55. Hupuczi P, Nagy B, Sziller I, et al. Characteristic laboratory changes in pregnancies
complicated by HELLP syndrome. Hypertens Pregnancy 2007; 26:389.
56. Knapen MF, van Altena AM, Peters WH, et al. Liver function following pregnancy
complicated by the HELLP syndrome. Br J Obstet Gynaecol 1998; 105:1208.
57. Neiger R, Contag SA, Coustan DR. The resolution of preeclampsia-related
thrombocytopenia. Obstet Gynecol 1991; 77:692.
58. Martin JN Jr, Blake PG, Lowry SL, et al. Pregnancy complicated by preeclampsia-
eclampsia with the syndrome of hemolysis, elevated liver enzymes, and low
platelet count: how rapid is postpartum recovery? Obstet Gynecol 1990; 76:737.
59. Mossayebi MH, Iyer NS, McLaren RA Jr, et al. HELLP syndrome at <23 weeks'
gestation: a systematic literature review. Am J Obstet Gynecol 2023; 229:502.
60. Gupta A, Joseph SR, Jeffries B. Managing a rare complication of HELLP syndrome in
Australia: Spontaneous liver haematoma in pregnancy. Aust N Z J Obstet Gynaecol
2021; 61:188.
61. Martin JN Jr, Rinehart BK, May WL, et al. The spectrum of severe preeclampsia:
comparative analysis by HELLP (hemolysis, elevated liver enzyme levels, and low
platelet count) syndrome classification. Am J Obstet Gynecol 1999; 180:1373.
62. Pauzner R, Dulitzky M, Carp H, et al. Hepatic infarctions during pregnancy are
associated with the antiphospholipid syndrome and in addition with complete or
incomplete HELLP syndrome. J Thromb Haemost 2003; 1:1758.
63. Jacquemyn Y, Jochems L, Duiker E, et al. Long-term renal function after HELLP
syndrome. Gynecol Obstet Invest 2004; 57:117.
64. Drakeley AJ, Le Roux PA, Anthony J, Penny J. Acute renal failure complicating
severe preeclampsia requiring admission to an obstetric intensive care unit. Am J
 Obstet Gynecol 2002; 186:253.
65. Abramovici D, Friedman SA, Mercer BM, et al. Neonatal outcome in severe
preeclampsia at 24 to 36 weeks' gestation: does the HELLP (hemolysis, elevated
liver enzymes, and low platelet count) syndrome matter? Am J Obstet Gynecol
1999; 180:221.
66. Sibai BM, Spinnato JA, Watson DL, et al. Pregnancy outcome in 303 cases with
severe preeclampsia. Obstet Gynecol 1984; 64:319.
67. 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.
68. Singhal N, Amin HJ, Pollard JK, et al. Maternal haemolysis, elevated liver enzymes
and low platelets syndrome: perinatal and neurodevelopmental neonatal
outcomes for infants weighing less than 1250 g. J Paediatr Child Health 2004;
40:121.
69. Dötsch J, Hohmann M, Kühl PG. Neonatal morbidity and mortality associated with
maternal haemolysis elevated liver enzymes and low platelets syndrome. Eur J
Pediatr 1997; 156:389.
70. 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.
71. Kändler C, Kevekordes B, Zenker M, et al. Prognosis of children born to mothers
with HELLP-syndrome. J Perinat Med 1998; 26:486.
72. Murray D, O'Riordan M, Geary M, et al. The HELLP syndrome: maternal and
perinatal outcome. Ir Med J 2001; 94:16.
73. Guzel AI, Kuyumcuoglu U, Celik Y. Are maternal and fetal parameters related to
perinatal mortality in HELLP syndrome? Arch Gynecol Obstet 2011; 283:1227.
74. Sibai BM, Ramadan MK, Chari RS, Friedman SA. Pregnancies complicated by HELLP
syndrome (hemolysis, elevated liver enzymes, and low platelets): subsequent
pregnancy outcome and long-term prognosis. Am J Obstet Gynecol 1995; 172:125.
75. van Oostwaard MF, Langenveld J, Schuit E, et al. Recurrence of hypertensive
disorders of pregnancy: an individual patient data metaanalysis. Am J Obstet
 Gynecol 2015; 212:624.e1.
76. Malmström O, Håberg SE, Morken NH. Probability and outcomes of second
pregnancy after HELLP syndrome in the first: A population-based registry study.
Acta Obstet Gynecol Scand 2020; 99:1206.

Topic 6778 Version 73.0

© 2024 UpToDate, Inc. All rights reserved.