19/5/2014 HELLP syndrome

http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&select 1/19
Official reprint from UpToDate
www.uptodate.com 2014 UpToDate
Author
Baha M Sibai, MD
Section Editors
Charles J Lockwood, MD, MHCM
Keith D Lindor, MD
Deputy Editor
Vanessa 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]:

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.

19/5/2014 HELLP syndrome

http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&select 2/19
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
[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]:
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 <5 percent is seen in 33 to 100 percent of women with TTP, but is rare or absent in those with HUS or HELLP
[32,34].

A high LDH level with only modest elevation of AST is more consistent with TTP than HELLP.
Pregnancies 34 weeks of gestation
Nonreassuring tests of fetal status (eg, biophysical profile, fetal heart rate testing)
Presence of severe maternal disease: multiorgan dysfunction, disseminated intravascular coagulation (DIC), liver infarction or hemorrhage, pulmonary edema, renal failure, or
abruptio placenta.

19/5/2014 HELLP syndrome

http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&select 3/19
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:
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].
In a study that treated 128 women with HELLP under 34 weeks of gestation with volume expansion and pharmacologic vasodilatation under invasive hemodynamic
monitoring, delivery was necessitated in 22/128 (17 percent) of patients within 48 hours; the remaining patients had a median prolongation of pregnancy of 15 days [36].
Although there was no maternal mortality or serious maternal morbidity and more than half (55/102) of the women had complete reversal of their laboratory abnormalities with
expectant management, 11 fetal and 7 neonatal deaths occurred.

In another series, 41 women with HELLP under 35 weeks of gestation were managed expectantly [37]. Delivery was required within 48 hours in 14/41 (34 percent), the
remaining patients had a median prolongation of pregnancy of 3 days and more than half (15/27) had compete reversal of their laboratory abnormalities [37]. However, there
were 10 fetal deaths.

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 <50,000 cells/microL) given dexamethasone had faster platelet count recovery and
shorter hospitalization than controls. We believe that this finding requires further investigation in prospective trials, given that the analysis was unplanned and the
severity of disease was not taken into account at randomization.

In the second trial, 114 postpartum women with HELLP syndrome were randomly assigned to receive either dexamethasone (10 mg) or placebo [44]. Use of dexamethasone
did not accelerate postpartum recovery of patients with HELLP syndrome: there was no difference between drug and placebo groups in the resolution of laboratory or clinical
parameters, frequency of maternal complications, need for rescue therapy, or length of hospitalization.

19/5/2014 HELLP syndrome

http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&select 4/19
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].
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.
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 5 to 6 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 10 to 12 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.)
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
19/5/2014 HELLP syndrome
http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&select 5/19
SUMMARY AND RECOMMENDATIONS
Management recommendations
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES
1. Stone JH. HELLP syndrome: hemolysis, elevated liver enzymes, and low platelets. JAMA 1998; 280:559.
2. 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.
3. 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.
4. Sibai BM. The HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): much ado about nothing? Am J Obstet Gynecol 1990; 162:311.
5. Lachmeijer AM, Arngrmsson R, Bastiaans EJ, et al. A genome-wide scan for preeclampsia in the Netherlands. Eur J Hum Genet 2001; 9:758.
6. 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.
7. 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.
8. Benedetto C, Marozio L, Tancredi A, et al. Biochemistry of HELLP syndrome. Adv Clin Chem 2011; 53:85.
9. Jebbink J, Wolters A, Fernando F, et al. Molecular genetics of preeclampsia and HELLP syndrome - a review. Biochim Biophys Acta 2012; 1822:1960.
10. Burwick RM, Feinberg BB. Eculizumab for the treatment of preeclampsia/HELLP syndrome. Placenta 2013; 34:201.
11. 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.
12. 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.
13. 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.
14. Wilcken B, Leung KC, Hammond J, et al. Pregnancy and fetal long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency. Lancet 1993; 341:407.
15. 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.
16. 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.
17. 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.
18. Isler CM, Rinehart BK, Terrone DA, et al. Maternal mortality associated with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Am J Obstet Gynecol
1999; 181:924.
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 <1 percent of pregnancies, but in 10 to 20
percent of pregnancies with severe preeclampsia/eclampsia. (See 'Incidence' above.)

The most common clinical presentation is abdominal pain and tenderness in the midepigastrium, right upper quadrant, or below the sternum. Many patients also have
nausea, vomiting, and malaise, which may be mistaken for a viral illness. Hypertension and proteinuria are present in approximately 85 percent of cases. Most cases of
HELLP are diagnosed between 28 and 36 weeks of gestation, but symptoms may present up to 7 days postpartum. (See 'Patient presentation' above.)

We base the diagnosis of HELLP on the presence of all of the following laboratory findings in pregnant women of appropriate gestational age (see 'Diagnosis' above):
Microangiopathic hemolytic anemia with schistocytes 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.
Serum aspartate aminotransferase (AST) >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.)

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.)

19/5/2014 HELLP syndrome

http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&select 6/19
19. Sibai BM. Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol 2004; 103:981.
20. 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.
21. 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.
22. Page LM, Girling JC. A novel cause for abnormal liver function tests in pregnancy and the puerperium: non-alcoholic fatty liver disease. BJOG 2011; 118:1532.
23. Pereira SP, O'Donohue J, Wendon J, Williams R. Maternal and perinatal outcome in severe pregnancy-related liver disease. Hepatology 1997; 26:1258.
24. Minakami H, Morikawa M, Yamada T, et al. Differentiation of acute fatty liver of pregnancy from syndrome of hemolysis, elevated liver enzymes and low platelet counts. J
Obstet Gynaecol Res 2014; 40:641.
25. Goel A, Ramakrishna B, Zachariah U, et al. How accurate are the Swansea criteria to diagnose acute fatty liver of pregnancy in predicting hepatic microvesicular steatosis?
Gut 2011; 60:138.
26. Innes AM, Seargeant LE, Balachandra K, et al. Hepatic carnitine palmitoyltransferase I deficiency presenting as maternal illness in pregnancy. Pediatr Res 2000; 47:43.
27. Matern D, Hart P, Murtha AP, et al. Acute fatty liver of pregnancy associated with short-chain acyl-coenzyme A dehydrogenase deficiency. J Pediatr 2001; 138:585.
28. Sibai BM, Ramadan MK. Acute renal failure in pregnancies complicated by hemolysis, elevated liver enzymes, and low platelets. Am J Obstet Gynecol 1993; 168:1682.
29. Weiner CP. Thrombotic microangiopathy in pregnancy and the postpartum period. Semin Hematol 1987; 24:119.
30. Egerman RS, Witlin AG, Friedman SA, Sibai BM. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in pregnancy: review of 11 cases. Am J Obstet
Gynecol 1996; 175:950.
31. Sullivan CA, Magann EF, Perry KG Jr, et al. The recurrence risk of the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP) in subsequent gestations.
Am J Obstet Gynecol 1994; 171:940.
32. 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.e1.
33. Martin JN Jr, Bailey AP, Rehberg JF, et al. Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955-2006. Am J Obstet Gynecol 2008; 199:98.
34. Lattuada A, Rossi E, Calzarossa C, et al. Mild to moderate reduction of a von Willebrand factor cleaving protease (ADAMTS-13) in pregnant women with HELLP
microangiopathic syndrome. Haematologica 2003; 88:1029.
35. 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.
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-eclampsia
without 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 and
elevated 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
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. Cochrane
Database 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 Obstet
Gynecol 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 Obstet
Gynecol 2004; 190:106.
51. Schwartz ML, Lien JM. Spontaneous liver hematoma in pregnancy not clearly associated with preeclampsia: a case presentation and literature review. Am J Obstet Gynecol
1997; 176:1328.
52. 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.
53. Grand'Maison S, Sauv N, Weber F, et al. Hepatic rupture in hemolysis, elevated liver enzymes, low platelets syndrome. Obstet Gynecol 2012; 119:617.
54. Wilson RH, Marshall BM. Postpartum rupture of a subcapsular hematoma of the liver. Acta Obstet Gynecol Scand 1992; 71:394.
55. Stevenson JT, Graham DJ. Hepatic hemorrhage and the HELLP syndrome: a surgeon's perspective. Am Surg 1995; 61:756.
56. 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.
57. 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.
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.
61. Ilbery M, Jones AR, Sampson J. Lupus anticoagulant and HELLP syndrome complicated by placental abruption, hepatic, dermal and adrenal infarction. Aust N Z J Obstet
Gynaecol 1995; 35:215.
62. Alsulyman OM, Castro MA, Zuckerman E, et al. Preeclampsia and liver infarction in early pregnancy associated with the antiphospholipid syndrome. Obstet Gynecol 1996;
88:644.
63. Seige M, Schweigart U, Moessmer G, et al. Extensive hepatic infarction caused by thrombosis of right portal vein branches and arterial vasospasm in HELLP syndrome
associated with homozygous factor V Leiden. Am J Gastroenterol 1998; 93:473.
19/5/2014 HELLP syndrome
http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&select 7/19
64. 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.
65. Chou MM, Chen YF, Kung HF, et al. Extensive hepatic infarction in severe preeclampsia as part of the HELLP syndrome (hemolysis, elevated liver enzymes, and low
platelets): evolution of CT findings and successful treatment with plasma exchange therapy. Taiwan J Obstet Gynecol 2012; 51:418.
66. Hupuczi P, Nagy B, Sziller I, et al. Characteristic laboratory changes in pregnancies complicated by HELLP syndrome. Hypertens Pregnancy 2007; 26:389.
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 platelet
count: how rapid is postpartum recovery? Obstet Gynecol 1990; 76:737.
68. 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.
69. Jacquemyn Y, Jochems L, Duiker E, et al. Long-term renal function after HELLP syndrome. Gynecol Obstet Invest 2004; 57:117.
70. 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.
71. 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.
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 Obstet
Gynecol 2003; 188:1504.
73. van Pampus MG, Wolf H, Mayruhu G, et al. Long-term follow-up in patients with a history of (H)ELLP syndrome. Hypertens Pregnancy 2001; 20:15.
74. Habli M, Eftekhari N, Wiebracht E, et al. Long-term maternal and subsequent pregnancy outcomes 5 years after hemolysis, elevated liver enzymes, and low platelets
(HELLP) syndrome. Am J Obstet Gynecol 2009; 201:385.e1.
75. Wst MD, Bolte AC, de Vries JI, et al. Pregnancy outcome after previous pregnancy complicated by hepatic rupture. Hypertens Pregnancy 2004; 23:29.
76. 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.
77. Sibai BM, Spinnato JA, Watson DL, et al. Pregnancy outcome in 303 cases with severe preeclampsia. Obstet Gynecol 1984; 64:319.
78. 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.
79. 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.
80. Dtsch J, Hohmann M, Khl PG. Neonatal morbidity and mortality associated with maternal haemolysis elevated liver enzymes and low platelets syndrome. Eur J Pediatr
1997; 156:389.
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.
82. Kndler C, Kevekordes B, Zenker M, et al. Prognosis of children born to mothers with HELLP-syndrome. J Perinat Med 1998; 26:486.
83. Murray D, O'Riordan M, Geary M, et al. The HELLP syndrome: maternal and perinatal outcome. Ir Med J 2001; 94:16.
84. Guzel AI, Kuyumcuoglu U, Celik Y. Are maternal and fetal parameters related to perinatal mortality in HELLP syndrome? Arch Gynecol Obstet 2011; 283:1227.
Topic 6778 Version 25.0
19/5/2014 HELLP syndrome
http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&select 8/19
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 <100,000/microliter
Serum creatinine >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.
Graphic 79977 Version 8.0
19/5/2014 HELLP syndrome
http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&select 9/19
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:
<100,000 platelets/microL
Renal abnormality:
Progressive renal insufficiency (serum creatinine >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.
Graphic 76975 Version 6.0
19/5/2014 HELLP syndrome
http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&selec 10/19
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
Graphic 64665 Version 1.0
19/5/2014 HELLP syndrome
http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&selec 11/19
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).
Graphic 59683 Version 2.0
19/5/2014 HELLP syndrome
http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&selec 12/19
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.
Graphic 53332 Version 5.0
19/5/2014 HELLP syndrome
http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&selec 13/19
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.
Graphic 57913 Version 2.0
19/5/2014 HELLP syndrome
http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&selec 14/19
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.
Graphic 69691 Version 1.0
19/5/2014 HELLP syndrome
http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&selec 15/19
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.
Graphic 89900 Version 1.0
19/5/2014 HELLP syndrome
http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&selec 16/19
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.
Graphic 89901 Version 1.0
19/5/2014 HELLP syndrome
http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&selec 17/19
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
19/5/2014 HELLP syndrome
http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&selec 18/19
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
19/5/2014 HELLP syndrome
http://www.uptodate.com/contents/hellp-syndrome?topicKey=OBGYN%2F6778&elapsedTimeMs=0&source=search_result&searchTerm=preeclampsia&selec 19/19
Di scl osures: Baha M Sibai, MD Nothing to disclose. Charles J Lockwood, MD, MHCM Nothing to disclose. Keith D Lindor, MD
Nothing to disclose. Vanessa A Barss, MD Employee of UpToDate, Inc. Equity Ownership/Stock Options: Merck; Pf izer; Abbvie.
Contributor disclosures are reviewed f or conf licts of interest by the editorial group. When f ound, these are addressed by vetting through
a multi-level review process, and through requirements f or ref erences to be provided to support the content. Appropriately ref erenced
content is required of all authors and must conf ormto UpToDate standards of evidence.
Conflict of interest policy
Disclosures