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HELLP Syndrome: Understanding and Management of A Pregnancy-Specifi C Disease
HELLP Syndrome: Understanding and Management of A Pregnancy-Specifi C Disease
REVIEW
Intensive Care Unit, Mitera Obstetric and Gynecological Hospital of Athens, Greece
J Obstet Gynaecol Downloaded from informahealthcare.com by University of Zuerich Zentrum fuer Zahn Mund und on 08/12/13
HELLP, a syndrome characterised by haemolysis, elevated endothelial damage (Hulstein et al. 2003). Recently, fetal disor-
liver enzymes and low platelets, a variant of pre-eclampsia/ ders of mitochondrial fatty acid oxidation have been associated
eclampsia, is a multisystemic disorder with an incidence of up with obstetric complications including HELLP syndrome; their
to 0.9% in all pregnancies and occurs in about one-quarter of action is not yet understood (Tyni et al. 1998).
pre-eclamptic patients. Most obstetricians presume that HELLP The aim of this paper is to summarise currently available
derives from an autoimmune reaction, leading to a materno data regarding epidemiology, aetiology, pathology, clinical pre-
fetal imbalance, with accompanying aggregation of platelets, sentation, classification, management and prognosis of HELLP
endothelial malfunction along with inborn errors of fatty acid syndrome and to discuss diagnostic problems and management
oxidative metabolism. HELLP is characterised by high mortal- doubts that affect clinicians and obstetricians.
ity and morbidity rates, leading to possibly life-threatening
complications regarding both the mother and the fetus. Delivery
is indicated if HELLP syndrome occurs after 34 gestational weeks Methods
or the fetal and/or maternal conditions deteriorate. Vaginal A systematic literature search for clinical reports and reviews
For personal use only.
delivery is preferable. Standard corticosteroid treatment is of on HELLP syndrome published between 1989 and 2011 were
uncertain clinical value in maternal HELLP syndrome. Future identified using PubMed and the Cochrane databases, and addi-
observations and research results may shed more light on tional cited works not detected in the initial search were obtained.
improving our understanding of the aspects of HELLP syndrome. Search words were HELLP syndrome, and HELLP syndrome
combined with diagnosis, clinical symptoms, complications,
Keywords: Eclampsia, HELLP syndrome, liver, management,
morbidity, mortality, management, treatment, prognosis
pregnancy
and recurrence. Publications were selected for review based
on original research, highly regarded earlier publications and
comprehensive reviews, while those publications considered as
Introduction relevant were used at the authors discretion.
Haemolysis, elevated liver enzymes and low platelets (HELLP)
syndrome, was first defined by Weinstein in 1982. It is a multi- Pathophysiology
systemic disorder which remains an important cause of maternal Haemolysis
and perinatal mortality and morbidity. The rapid decrease of the erythrocyte number during the full
Many researchers and clinicians consider this particular syn- presentation of HELLP syndrome is believed to result from
drome as a variant of another peculiar disease of pregnancy, pre- the cellular damage due to fibrin deposition, leading to fragmen-
eclampsia (Habli et al. 2009), whereas other physicians consider tation of the red blood cells (Doshi and Zucker 2003; Moake
it to be a totally different expression of the rejection of the fetus 2009). This particular finding is consistent with microangio-
in the late trimester of pregnancy, due to maternofetal immune pathic haemolytic anaemia, with the distorted red cells seen in
imbalance (Tung et al. 2001; Fang et al. 2008b). the microscope (Burr cells) along with schistocytes, as well as
HELLP syndrome has an incidence of 0.170.85% of all preg- polychromasia on peripheral blood smear (Baxter and Weinstein
nancies, while the risk of recurrence in a subsequent pregnancy 2004). In recent studies, many similarities between haemolytic
is about 1927% (Isler et al. 2003). It is a multisystem disease uraemic syndrome and HELLP syndrome have been reported
which is characterised by abnormal vascular tone, vasospasm in the field of molecular mechanisms between blood cells,
and coagulation defects. Although, its pathophysiology remains which interact with one another, proposing a quite similar defec-
partially unknown, activation of endothelial cells may lead to tive regulation between these two different pathological entities
release of von Willebrand factor multimers, which are highly (Fang et al. 2008a,b).
reactive with platelets. The syndrome seems to be the final Widely accessible markers of haemolysis can be the levels
manifestation of some insult that leads to microvascular endothe- of lactic dehydrogenase and indirect (unconjugated) bilirubin.
lial damage and intravascular platelet activation. With platelet Moreover, the presence of reticulocytes can be explained as an
activation, thromboxane A and serotonin are released, causing effort of the organism to withstand this condition and release
vasospasm, platelet agglutination and aggregations and further the immature cells as a compensatory reflect (Haram et al.
Correspondence: S. Gourgiotis, Intensive Care Unit, Mitera Obstetric and Gynecological Hospital of Athens, Erythrou Stavrou 6 and Kissias str PO Code
151 23, Maroussi, Athens, Greece. E-mail: [email protected]
332 S. Aloizos et al.
2009). According to recent findings, a more sensitive and precise Low platelet count
indicator of haemolysis is the unusually low level of haptoglobin Thrombocytopenia (platelets 150 109/l) in pregnancy may be
(van Runnard Heimel et al. 2005); nevertheless, its assessment caused by gestational thrombocytopenia (59%), immune throm-
is rarely included in the routine laboratory screening of the bocytopenic purpura (11%), pre-eclampsia (10%) or HELLP syn-
patients. drome (12%) (Thangaratinam et al. 2011). Platelets 100 109/l
are relatively rare in pre-eclampsia and gestational thrombocy-
topenia, frequent in immune thrombocytopenic purpura and
Liver enzymes elevation
obligatory in the HELLP syndrome (according to the Sibai
The liver involvement in HELLP syndrome is similar to the
definition) (Sibai 2004b). Decreased platelets count in the HELLP
alterations presented in pre-eclampsia. Typical histological
syndrome is due to their increased consumption. Platelets are
findings of liver biopsies of patients include fibrin deposition
activated, and adhere to damaged vascular endothelial cells,
intravascularly, which can lead to obstruction of the sinusoids
resulting in increased platelet turnover with shorter lifespan
due to hyaline deposits of fibrin-like material, blood congestion
(Baxter and Weinstein 2004).
and elevated intrahepatic pressure, resulting in focal and/or
J Obstet Gynaecol Downloaded from informahealthcare.com by University of Zuerich Zentrum fuer Zahn Mund und on 08/12/13
PLTs, platelets; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; ALT, matosus, antiphospholipid syndrome), highlighting the need
alanine aminotransferase.
for accurate differential diagnosis of the syndrome.
Thus, it is evident an immediate response is profound in this
situation. A chemistry panel including blood nitrogen urea,
since there is no difference when taking into account the levels
creatinine, liver function enzymes, LDH, glucose, total bilirubin
of AST and ALT. Both count as equal, only one elevated is needed
and uric acid is the first step of the approach to the syndrome.
in order to classify the patient.
A complete evaluation of the blood parameters is also essential,
The introduction and clinical application of these classifi-
indicating the abnormalities in the erythrocyte count, the periph-
cation systems enabled the standardisation of the diagnosis of
eral smear, PT and aPTT prolongation, and fibrinogen levels
HELLP syndrome. Nevertheless, the complex pathogenesis of the
(Poo and Gngora 2006).
syndrome may require additional and more specific laboratory
Liver imaging is important for the evaluation of subcapsular
examinations, for instance assessment of circulating autoanti-
or intraparenchymal haemorrhage and hepatic rupture.
bodies or special clotting tests.
Diagnostic tools include ultrasound (U/S), computed tomog-
Diagnosis raphy (CT) and magnetic resonance imaging (MRI) (Martin
et al. 1999; Gilboa et al. 2006). In pregnant women, U/S and MRI
The diagnosis of HELLP syndrome is suspected in pregnant
are preferred due to the absence of ionising radiation. CT is the
For personal use only.
Systemic lupus erythematosus the late 2nd or the 3rd trimester, but it has also been reported
4 Rare diseases that mimic Haemolytic uraemic syndrome during the immediate postpartum period (Reck et al. 2001). In
HELLP syndrome Thrombotic thrombocytopenic this case, and if failure of conservative or minimally-invasive
purpura treatment occurs, emergency surgery is likely to be the only
therapeutic option. It is very important to remember that the
risk of hepatic rupture in patients with HELLP syndrome is
septic shock, acute renal failure and hepatic haemorrhage due not reduced after labour or the emergency extraction of the
to hepatic rupture (Barton and Sibai 2009; Zeeman 2009). fetus, but it may present 2448 h after labour and/or complete
As we noticed, differences in the outcome of the neonates regression of the syndrome.
depend on the study publication, while a low gestational age at
delivery is the main problem rather than HELLP itself. Infants Neonate
born to mothers with the HELLP syndrome may develop throm- Regarding the fetus-related complications of HELLP syndrome,
bocytopenia and neurological complications. However, most the most common ones are the necessity of pre-term delivery;
neonates born to women with HELLP have a normal long-term severe neonatal hypoglycaemia; thrombocytopenia; respira-
development. tory distress syndrome; low birth weight; hyperbilirubinaemia;
Nevertheless, up to the present time, although the severity of
For personal use only.
neonatal outcome in cases with advanced gestational age. tions, which may lead to systematic dysfunction (OBrien and
Kandler et al. (1998) reported that in the time span between Barton 2005; Mihu et al. 2007).
6 and 72 months (median 24 months) after delivery, 90% of When one or more of the numerous complications are present,
children born from mothers with HELLP showed normal devel- an aggressive approach and treatment will minimise the risks of
opment or only minor disabilities. both mother and the fetus. A combination of plasma exchanges
and fresh frozen plasma units is able to sustain the platelet count
Treatment and the fluid restriction will comprehend to avoid the cerebral
oedema (Bayraktarolu et al. 2006; Myers 2010). In cases of con-
The management of patients with pre-eclampsia and HELLP syn-
comitant renal failure, haemodialysis is the gold standard thera-
drome is controversial. Most therapeutic modalities are similar to
peutic approach. For patients with a platelet count 70,000/l,
those applied for severe pre-eclampsia. Patients should be imme-
or with coagulation parameters far from the normal ranges, the
diately referred to a tertiary care centre (OBrien and Barton 2005).
spinal or epidural anaesthesia is not suggested, due to possible
Treatment should be performed in intensive care units (ICUs)
bleeding. When needed, transfusion of packed erythrocytes
with dialysis and ventilatory support in severe cases, and consist of
J Obstet Gynaecol Downloaded from informahealthcare.com by University of Zuerich Zentrum fuer Zahn Mund und on 08/12/13
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