A systematic literature search for clinical reports and reviews published between 2000 and 2008 was undertaken using Pub Med and the Cochrane databases. Search words were "HELLP syndrome", and "HELLP syndrome" combined with "diagnosis", respective "clinical symptoms", "complications", "morbidity", "mortality", "management", "treatment", "corticosteroid", "prognosis", "delivery", "post-partum" and "recurrence". Publications were selected for review based on original research, highly regarded earlier publications and comprehensive reviews. The abstracts were read and those publications considered to be relevant were used at the authors' discretion. Some publications have also been found in the reference list in previous publications.
Occurrence and clinical symptoms
The HELLP syndrome occurs in about 0.5 to 0.9% of all pregnancies and in 10 to 20% of cases with severe preeclampsia [
15,
16]. In about 70% of the cases, the HELLP syndrome develops before delivery [
14] with a peak frequency between the 27th and 37th gestational weeks; 10% occur before the 27th week, and 20% beyond the 37th gestational week [
6]. The mean age of pregnant women with HELLP syndrome is usually higher than in women with preeclampsia [
3,
17]. Most white women with HELLP are multiparous [
10]. In the post-partum period the HELLP syndrome usually develops within the first 48 hours in women who have had proteinuria and hypertension prior to delivery [
14]. Although variable, the onset of the HELLP syndrome is usually rapid [
7]. The majority of women with the HELLP syndrome have had hypertension and proteinuria, which may be absent in 10–20% of the cases [
9]. Excessive weight gain and generalized oedema precede the syndrome in more than 50% of the cases [
8].
Typical clinical symptoms are right upper abdominal quadrant or epigastric pain, nausea and vomiting. The upper abdominal pain may be fluctuating, colic-like [
9,
18]. Many patients report a history of malaise some days before presentation [
9]. Up to 30–60% of women have headache; about 20% visual symptoms [
9]. However, women with a HELLP syndrome might also have unspecific symptoms or subtle signs of preeclampsia or non-specific viral syndrome-like symptoms [
9]. The symptoms usually continuously progress and their intensity often changes spontaneously. The HELLP syndrome is characterized by exacerbation during the night and recovery during the day [
19].
Women with partial HELLP syndrome have fewer symptoms and develop less complications than those with the complete form [
3]. However, a partial or incomplete HELLP syndrome may develop to a complete form of the disorder [
7]. Partial or total reversal of the syndrome may also occasionally occur, albeit rarely [
18,
20].
The triad signs of haemolysis, elevated liver enzymes and thrombocytopenia
Haemolysis, one of the major characteristics of the disorder, is due to a microangiopathic haemolytic anaemia (MAHA). Red cell fragmentation caused by high-velocity passage through damaged endothelium appears to represent the extent of small vessel involvement with intima damage, endothelial dysfunction and fibrin deposition. Presence of fragmented (schizocytes) or contracted red cells with spicula (Burr cells) in the peripheral blood smear reflects the haemolytic process and strongly suggests the development of MAHA [
6,
21]. Polychromatic red cells are also seen in blood smears, and increased reticulocyte counts reflect the compensatory release of immature red cells into peripheral blood. Destruction of red blood cells by haemolysis causes increased serum lactate dehydrogenase (LDH) levels and decreased haemoglobin concentrations [
22,
23]. Haemoglobinaemia or haemoglobinuria is macroscopically recognizable in about 10% of the women [
24]. Liberated haemoglobin is converted to unconjugated bilirubin in the spleen or may be bound in the plasma by haptoglobin. The haemoglobin-haptoglobin complex is cleared quickly by the liver, leading to low or undetectable haptoglobin levels in the blood, even with moderate haemolysis [
22,
23]. Low haptoglobin concentration (< 1 g/L – < 0.4 g/L) can be used to diagnose haemolysis [
23‐
26] and is the preferred marker of haemolysis [
27]. Thus, the diagnosis of haemolysis is supported by high LDH concentration and the presence of unconjugated bilirubin, but the demonstration of low or undetectable haptoglobin concentration is a more specific indicator.
Elevation of liver enzymes may reflect the haemolytic process as well as liver involvement. Haemolysis contributes substantially to the elevated levels of LDH, whereas enhanced asparate aminotransferase (AST) and alanine aminotransferase (ALAT) levels are mostly due to liver injury. Plasma glutathione S-transferase-a1 (α-GST or GST-a1) may provide a more sensitive indicator for acute liver damage than AST and ALAT, and allow earlier recognition [
28]. However, measurement of α-GST is not widely available, and has not yet found its place in the routine diagnostic procedure [
24].
Thrombocytopenia (platelets (PLTs) < 150·10
9/L) in pregnancy may be caused by gestational thrombocytopenia (GT) (59%), immune thrombocytopenic purpura (ITP) (11%), preeclampsia (10%), and the HELLP syndrome (12%)[
29]. PLTs < 100·10
9/L are relatively rare in preeclampsia and gestational thrombocytopenia, frequent in ITP and obligatory in the HELLP syndrome (according to the Sibai definition). Decreased PLT count in the HELLP syndrome is due to their increased consumption. Platelets are activated, and adhere to damaged vascular endothelial cells, resulting in increased platelet turnover with shorter lifespan [
21,
30,
31].
Diagnostic criteria
At present, there are two major definitions for diagnosing the HELLP syndrome. In the Tennessee Classification System, Sibai has proposed strict criteria for "true" or "complete" HELLP syndrome (Table
1) [
8,
9]. Intravascular haemolysis is diagnosed by abnormal peripheral blood smear, increased serum bilirubin (≥ 20.5 μmol/L or ≥ 1.2 mg/100 mL) and elevated LDH levels (> 600 units/L (U/L) [
8,
32].
Table 1
Main diagnostic criteria of the HELLP syndrome
1 | Platelets ≤ 100·109/L | Platelets ≤ 50·109/L |
| AST ≥ 70 IU/L | AST or ALT ≥ 70 IU/L |
| LDH ≥ 600 IU/L | LDH ≥ 600 IU/L |
2 | | Platelets ≤ 100·109/L ≥ 50·109/L |
| | AST or ALT ≥ 70 IU/L |
| | LDH ≥ 600 IU/L |
3 | | Platelets ≤ 150·109/L ≥ 100·109/L |
| | AST or ALT ≥ 40 IU/L |
| | LDH ≥ 600 IU/L |
In The Mississippi-Triple Class System, a further classification of the disorder is based on the nadir PLT count any time during the course of the disease (Table
1) [
7]. Class 1 and class 2 are associated with haemolysis (LDH > 600 U/L) and elevated AST (≥ 70 U/L) concentration, while class 3 requires only LDH > 600 U/L and AST ≥ 40 U/L in addition to the specific PLT count [
7,
33,
34]. Class 3 HELLP syndrome is considered as a clinical significant transition stage or a phase of the HELLP syndrome which has the ability of progression [
34].
The diagnosis of the HELLP syndromes has often been based on different criteria [
9]. The condition can be diagnosed simply on biochemical evidence [
4,
9,
14,
35‐
37]. Some authors require the presence of severe preeclampsia together with biochemical substantiation to diagnose HELLP [
5,
38‐
42]. Others deal with the HELLP syndrome as partial or incomplete HELLP [
43,
44]. A number of studies have included women with lack of suspicion or evidence of haemolysis. The syndrome ELLP has been described where there has been no haemolysis [
15,
45]. The use of different definitions makes comparison of published data difficult [
9]. According to Smulian
et al. the threshold of normal LDH values may be much lower than 600 U/L depending on the laboratory method adopted [
41]. Visser and Wallenburg used ALAT > 30 U/L to define abnormality (2 SD above mean in hospital) [
20]. Clearly, the analytical method used is important for the diagnostic reference range.
Differential diagnosis
The HELLP syndrome may be misdiagnosed as viral hepatitis, cholangitis and other acute diseases (Table
2) [
6,
46]. Other less common, but serious conditions that may mimic HELLP, include ITP, acute fatty liver of pregnancy (AFLP), haemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP) and systemic lupus erythematosus (SLE) [
21,
32]. These conditions are associated with high maternal mortality and may cause long-term squeals [
32]. They may be mistaken for a HELLP syndrome and a careful diagnostic evaluation is required as their therapy is quite different.
Table 2
Differential diagnosis of the HELLP syndrome.
1. Diseases related to pregnancy |
Benign thrombocytopenia of pregnancy |
Acute fatty liver of pregnancy (AFLP) |
2. Infectious and inflammatory diseases, not specifically related to pregnancy: |
Virus hepatitis |
Cholangitis |
Cholecystitis |
Upper urinary tract infection |
Gastritis |
Gastric ulcer |
Acute pancreatitis |
3. Thrombocytopenia |
Immunologic thrombocytopenia (ITP) |
Folate deficiency |
Systemic lupus erythematosus (SLE) |
Antiphospholipid syndrome (APS) |
4. Rare diseases that may mimic HELLP syndrome |
Thrombotic thrombocytopenic purpura (TTP) |
Haemolytic uremic syndrome (HUS) |
Clinical signs of AFLP vary and there is significant overlap in clinical and biochemical features with the HELLP syndrome [
47]. AFLP typically occurs between the 30th and 38th gestational weeks with a 1 to 2 week history of malaise, anorexia, nausea, vomiting, mid epigastric or right upper abdominal pain, headache and jaundice. Hypertension and proteinuria are usually absent. Further examination reveals haemoconcentration, metabolic acidosis, acute liver failure and low grade disseminated intravascular coagulation (DIC) with normal or moderately subnormal PLT count, prolonged prothrombin time (PT) and partial thromboplastin time (PTT), low serum fibrinogen and antithrombin concentrations [
32,
47,
48]. Abnormal blood tests also include leucocytosis, increased levels of creatinine, uric acid, ammonium and liver enzymes such as alkaline phosphatase, AST, ALAT and bilirubin [
32,
49]. Hypoglycemia and prolongation of prothrombin time may distinguish AFLP from the HELLP syndrome [
47]. Ultrasound examination of the liver may reveal increased echogenicity in severe cases of AFLP. Computerized tomography (CT) can well show decreased or diffuse attenuation in the liver. Liver biopsy is recommended as the standard procedure to confirm the diagnosis, but requires an acceptable haemostatic function [
32]. Gastrointestinal bleeding, acute renal failure and pancreatitis may complicate AFLP. Most women improve in the course of 1 to 4 weeks post-partum, but AFLP may recur in next pregnancy [
47].
ITP is a clinical syndrome with thrombocytopenia which may be manifested as a bleeding disorder with purpura and petechiae. Pregnancy does not increase the incidence of ITP, nor does it exacerbate a preexisting disease. Even with a very low platelet count there is in most cases neither maternal nor fetal morbidity or mortality [
29,
50,
51].
HUS and TTP are thrombotic microangiopathies which share some of the pathophysiological characteristics of the HELLP syndrome including endothelial injury, platelet aggregation, microthrombi, thrombocytopenia and anaemia [
49]. Abnormal blood smear, increased LDH and creatinine levels may help in the differentiation. The microvascular injury in HUS affects mainly the kidneys [
32]. HUS develops usually in the post-partum period, with signs and symptoms of renal failure [
9]. However, most cases arise in children and adolescents caused by a specific enterotoxin produced by Escherichia coli O157:H7. Rare forms may be due to a genetic abnormality in the complement system [
52]. TTP, which is an extremely rare condition during pregnancy, is characterized by neurological dysfunction, fever, abdominal pain and bleeding. The spectrum of neurological abnormalities spans from headache to visual disturbances, confusion, aphasia, transient paresis, weakness and seizures. High levels of high-molecular weight von Willebrand factor in maternal serum reflect the virtual absence of the metalloprotease ADAMTS13 enzyme which is required to control the level of the factor [
32,
53]. Specific tests for this hereditary condition are not readily available in routine clinical laboratories [
32]. The mortality of HUS and TTP has decreased due to the use of plasma exchange and intensive care [
52].
SLE is an autoimmune disorder characterized by deposits of antigen-antibody complexes in capillaries, with mild to severe clinical findings. SLE may affect multiple organ systems (kidneys, lungs, heart, liver and brain). The clinical and laboratory findings in women with lupus nephritis are similar to those with severe preeclampsia. Antiphospholipid antibodies (lupus anticoagulant and/or anticardiolipin antibodies) are present in 30–40% of the cases, while thrombocytopenia occurs in 40–50% and haemolytic anaemia in 14–23% of the women with SLE. Cerebral lesions and symptoms may develop because of vasculitis and/or cerebro-vascular occlusion that might lead to seizures [
32]. In the so-called antiphospholipid syndrome (APS) antiphospholipid antibodies are associated with recurrent thrombosis (in arteries and veins) and pregnancy loss. APS may also occur as a primary disease, unrelated to SLE. Development of HELLP syndrome in women with an established APS syndrome may be more frequent than previously thought [
54].
Folate deficiency is common in pregnancy, but its progression to megaloblastosis is rare. Haemolytic anaemia, thrombocytopenia, and coagulopathy due to folate deficiency may mimic the incomplete HELLP syndrome [
55].
Complications of the HELLP syndrome
The HELLP syndrome is associated with both maternal and neonatal complications. Frequencies of reported serious complications are summarized in table
3[
56‐
77].
Table 3
Complications reported in the HELLP syndrome
Eclampsia | 4–9 | |
Abruptio placentae
| 9–20 | |
DIC | 5–561
| |
Acute renal failure | 7–36 | |
Severe ascites | 4–11 | |
Cerebral oedema | 1–8 | |
Pulmonary oedema | 3–10 | |
Wound hematoma/infection2
| 7–14 | |
Subcapsular liver hematoma | Between 0.9% and <2% | |
Liver rupture | >200 cases or about 1.8% | |
Hepatic infarction | >30 cases combined with APS | |
Recurrent thrombosis | Associated with prothrombin gene 20210a mutation | |
Retinal detachment | 1 | |
Cerebral infarction | Few case reports | |
Cerebral Haemorrhage | 1.5–403
| |
Maternal death | 1–25 | |
Foetal/neonatal complications
| | |
Perinatal death | 7.4–34 | |
IUGR | 38–61 | |
Preterm delivery4
| 70 (15% < 28 gestational weeks) | |
Neonatal thrombocytopenia 5
| 15–50 | |
RDS | 5.7–40 | |
Laboratory thresholds that indicate more than 75% risk of serious maternal morbidity are LDH concentration > 1400 U/L, AST > 150 U/L, ALAT > 100 U/L, and uric acid concentration >7.8 mg/100 ml (> 460 μmol/L)[
6]. Interestingly, clinical symptoms, such as headache, visual changes, epigastric pain and nausea-vomiting, have been suggested to be better predictors of adverse maternal outcome than laboratory parameters [
57].
Spontaneous rupture of a subcapsular liver haematoma in pregnancy is a rare, but life threatening complication that occurs 1 in 40,000 to 1 in 250,000 deliveries [
63] and about 1% to < 2% of the cases with the HELLP syndrome. Rupture most often occurs in the right liver lobe [
9,
14,
61‐
64]. The symptoms are sudden-onset severe pain in the epigastric and right upper abdominal quadrant radiating to the back, right shoulder pain, anaemia and hypotension. The condition may be diagnosed by ultrasound, CT or magnetic resonance imaging (MRI) examination [
61‐
63,
78]. Hepatic rupture may also occur in the post-partum period [
79]. A few cases of liver infarctions associated with antiphospholipid syndrome and HELLP syndrome have been reported [
66]. Even recurrent deep vein thromboses and palmar skin lesions have been reported in a woman with prothrombin gene 20210a mutation and antiphospholipid antibodies complicated by the HELLP syndrome [
67].
More common and serious maternal complications are
abruptio placentae, DIC and subsequent severe post-partum bleeding (Table
3) [
5]. Bilateral permanent visual loss associated with retinopathy (Pursher-like) is a rare ophthalmic complication during pregnancy [
80]. In the literature there are several case reports on cerebral bleeding associated with the HELLP syndrome [
68‐
71]. In a report by Sibai
et al. on the outcome of 442 pregnancies complicated by HELLP cerebral bleeding was not mentioned as a complication [
14]. Audibert
et al. report cerebral bleeding to occur in 1.5% of the cases [
3]. Contrary to this, in a highly selected group of 37 women with the HELLP syndrome that was transferred to an obstetric intensive care unit in Turkey, 15 women (40%) had cerebral haemorrhage. In this study CT and MRI were used as diagnostic tools [
36]. The risk of stroke is not increased during pregnancy itself. However, the risk of cerebral infarction and intracerebral haemorrhage is increased some weeks after delivery [
81]. This is reflected by some case reports of cerebral infarction after delivery as a complication to the HELLP syndrome [
68‐
71]. Life-threatening neurological complications of the HELLP syndrome are rare, but incorporate large cerebral or brain stem haemorrhage, thrombosis and infarctions or cerebral oedema complicated by brain herniation [
6]. Wound haematoma and infection are frequent phenomena in women with the HELLP syndrome undergoing Caesarean section [
82].
DIC
Activation of vascular endothelium and of platelets, haemolysis and liver damage are the basic pathophysiological features characteristic for the HELLP syndrome, each predisposing to DIC [
83,
84]. In a retrospective cohort study, 38% of pregnant women with the HELLP syndrome developed DIC (PLTs < 100·10
9/L, low serum fibrinogen concentration (< 3 g/L), fibrin degradation products (FDP) (>40 μg/ml = 40 mg/L) most often related to placental abruption [
45]. Low antithrombin concentration may be caused by liver dysfunction with decreased synthesis, and by increased consumption in DIC. Paternoster
et al. reported that women with a HELLP syndrome had higher concentration of fibronectin and D-dimer and lower antithrombin levels than in normal pregnancy and in preeclampsia [
85].
Abruptio placentae associated with the HELLP syndrome increases the risk of DIC substantially as well as the risk of pulmonary oedema, renal failure (oliguria, anuria, high serum creatinine levels) and the need for blood transfusion [
9,
35,
86]. A contributing factor for acute renal failure is microangiopathy and DIC [
4,
59,
60]. Visual disturbances, including retinal detachment, vitreal haemorrhage and cortical blindness, are infrequent complications in which DIC probably contributes [
34].
Maternal mortality
In a large retrospective cohort study comprising 442 pregnancies complicated by the HELLP syndrome, the maternal mortality was 1.1% [
14], which is in accordance with other reports [
3,
9,
87,
88]. However, higher maternal mortality, up to 25%, has been reported [
11]. Unexpected rapid death from HELLP may require forensic expertise [
89]. Isler
et al. found cerebral haemorrhage or stroke to be the primary cause of death in 26% and the most contributing factor in another 45% of the deaths [
90]. Maternal mortality rate in hepatic rupture ranges from 18 to 86% [
91].
HELLP, perinatal mortality and morbidity
Perinatal mortality and morbidity are considerably higher in the HELLP syndrome than that of the mothers, and are primarily dependent on the gestational age when the condition develops [
74,
92]. The perinatal mortality rate related to the HELLP syndrome is between 7.4% and 34% [
9,
72,
73]. Neonates delivered before completed 32 weeks' gestation have the highest risk of perinatal death [
74,
92]. According to Gul
et al. the perinatal mortality was 34% before 32 weeks' gestation, and 8% after the 32nd gestational week [
72]. Prematurity, placental insufficiency, with or without intrauterine growth restriction (IUGR) and
abruptio placentae, are the leading causes of neonatal death [
6,
15,
21]. Hepatic rupture has a perinatal mortality that can reach 80% [
91].
Neonatal thrombocytopenia occurs in between 15% and 38% of cases [
5,
93] and is a significant risk factor for both intraventricular haemorrhage (IVH) and long-term neurological complications [
5,
94].
The neonatal outcome of the HELLP syndrome represents a controversy [
94]. Some authors report that infants born to mothers with a HELLP syndrome are more likely to be small for gestational age (SGA) and to have increased risk of perinatal asphyxia and RDS [
94] and that the respiratory and cardiovascular morbidity may be further aggravated by maternal HELLP occurring before 32 weeks' gestation [
95]. A retrospective study was published in 2003 by Roelofsen
et al. on the outcome of infants born after pregnancies complicated by HELLP or ELLP syndrome. The gestational age was 29.9 in the HELLP group and 30.3 weeks in the ELLP group. 64% were born before 32 weeks' gestation. Cerebral haemorrhage occurred in 3 of the infants in the HELLP group (all had thrombocytopenia (9–42·10
9/L), none in the ELLP group. After 18 months four infants belonging to the HELLP group had major handicaps, none in the ELLP group, making a total adverse outcome of 22.8% [
44].
Other authors inform that infants born to mothers with the HELLP syndrome are not at increased risk of morbidity compared to otherwise healthy infants of the same gestational age [
92,
93,
96,
97] and that that gestational age at delivery and birth weight primarily affected the perinatal mortality rather than the severity of the hypertensive disease [
73]. Consequently also typical complications following preterm delivery in itself are reported, like bronchopulmonary dysplasia (BPD) cerebral haemorrhage and persisting
ductus arteriosus in HELLP [
44].
Murray
et al. published in 2001 the outcome of 20 cases of the HELLP syndrome over a 5-year period. 85% were delivered by Caesarean section within 24 hours of diagnosis. 65% were preterm. The mean gestation at delivery was 33.5 weeks and the mean birth weight 1923 g. 40% of the neonates developed respiratory distress syndrome (RDS). The neonatal morbidity was most closely related to the gestation at delivery [
77].
Analysis of the perinatal and neonatal data for women diagnosed with HELLP from 1993 to 1996 was performed by Singhal
et al. who compared the neurodevelopmental outcome of HELLP a group of birth weight matched controls. A total of 109 infants (mean gestational age 32.6 weeks, mean birth weight 1766 g) were born by 104 women with HELLP syndrome. There were no significant differences in gender, Apgar score, need for resuscitation, RDS, sepsis, NEC or death in the neonatal unit, suggesting that infants born to mothers with a HELLP syndrome are not at increased risk for mortality or morbidity and that the majority of neonatal complications were attributable to prematurity [
94]. There was a significant decrease in mortality and morbidity with increasing gestational age and birth weight. No significant differences in neonatal mortality and morbidity were found in infants weighing less than 1250 g compared to the weight matched control group. At 3 years of age, the HELLP group had fewer children with cerebral palsy (CP) and mental disability [
94].
Kandler
et al. reported that in the time span between 6 and 72 months (median 24 months) after delivery, 90% of children born from mothers with HELLP showed normal development or only minor disabilities. The mean gestational age was 33 weeks and the mean birth weight 1671 g [
97]. However, the neonatal outcome is poor before 25 weeks' gestation or with birth weights less than 700 g; after 26 weeks' gestation or in infants weighing more than 700 g it is substantially better [
74,
92].
We assume that differences in the outcome of the neonates depend on the study publication and also reflect the level of neonatal care. Infants born from mothers with the HELLP syndrome may develop thrombocytopenia and associated CP. However, it seems that a low gestational age at delivery is the main problem rather then HELLP in itself. Most neonates born from a woman with HELLP have a normal long-term development.
Management of pregnant women with HELLP syndrome
In general, there are three major options for the management of women with severe preeclampsia and HELLP syndrome [
7,
9,
72,
98]. These include:
1) Immediate delivery which is the primary choice at 34 weeks' gestation or later.
2) Delivery within 48 hours after evaluation, stabilization of the maternal clinical condition and CS treatment. At 27 to 34 weeks of gestation, this option appears appropriate and rational for the majority of cases.
3) Expectant (conservative) management for more than 48–72 hours may be considered in pregnant women before 27 weeks' gestation. In this situation, CS treatment is often used, but the regimens vary considerably.
Conservative management (> 48 hours)
Large randomized clinical trials aimed to compare conservative versus aggressive management with immediate delivery of women with the HELLP syndrome are missing. However, expectant management before completed 34 weeks' gestation may be an acceptable option in selected cases if it is performed in tertiary care units under close maternal and foetal surveillance (e.g. antihypertensive treatment, ultrasound and Doppler examination) [
99,
100]. Possible advantages due to limited prolongation of pregnancy should be carefully weighed against the increased risks for maternal and foetal complications (
abruptio placentae, acute renal failure, pulmonary oedema, DIC, perinatal and maternal death) [
10]. If the maternal condition worsens, immediate Caesarean section is inevitable [
99,
100]. Conservative treatment is contraindicated in women with DIC [
58].
The benefit of temporizing management of HELLP syndrome is questioned [
10,
101]; some authors warn against expectant management to optimize maternal condition before delivery beyond 24–48 hours [
10] or conservative management is disregarded [
73]. However, expectant management of pregnant women with HELLP syndrome remote from term is common practice in the Netherlands, conditional on the safety of the mother [
20,
102].
Different definitions and classifications have up to now been used to diagnose the HELLP syndrome. This has limited the usefulness of many clinical reports. The Tennessee and Mississippi classifications are well suited to facilitate comparisons. Classifications used in future reports should be restricted to one of these.
Neither randomized trials nor Cochrane evaluations regarding delivery in women with the HELLP syndrome have been performed. In order to reduce the risk of potentially serious complications, there is consensus that early delivery is indicated when the HELLP syndrome develops after 34 weeks of pregnancy. Expectant management and the use of CS in the HELLP syndrome developed prior to 34 weeks of gestation are main controversial issues. There is no general agreement on timing of delivery and the best method of delivery. In deliveries in the time-span between 24 and 34 weeks' gestation, a standard CS course is usually recommended after stabilization of the maternal condition, followed by delivery 24 hours later. Although a maternal benefit has been demonstrated for patients with severe preeclampsia, this effect seems to be limited or lacking in patients with the HELLP syndrome. Repeated CS dosage and high-dose dexamethasone treatment can at present not be recommended. There is a definite need both in antepartum and post-partum HELLP patients for adequately sized, randomized, placebo-controlled trials regarding dosage of CS, as well as high-dose dexamethasone versus standard CS dosage. Better insight in the complex pathophysiology of the HELLP syndrome may lead to new treatment alternatives and improved clinical management. A well designed multicenter study testing the benefit of antithrombin to counteract DIC in the HELLP syndrome should be encouraged.