Practice Essentials

HELLP syndrome, named for 3 features of the disease (hemolysis, elevated

liver enzyme levels, and low platelet levels), is a life-threatening condition
that can potentially complicate pregnancy. HELLP was once known as edema-
proteinuria-hypertension gestosis type B in the early 20th century and was
later renamed in 1982 by Louis Weinstein.
Although the idea is controversial, some propose that HELLP is a severe form
of preeclampsia, which, in turn, is defined as gestational hypertension
accompanied by proteinuria after the 20th week of gestation. Others believe
that HELLP syndrome is an entity of its own. Although the cause of HELLP
syndrome is unknown, certain risk factors, including a maternal age of older
than 34 years, multiparity, and European descent, have been described. [1, 2, 3]
There is no known preventive management.
Patients with HELLP syndrome should be educated on the risk of maternal
and fetal morbidity and mortality in future pregnancies.
Pathophysiology
HELLP is a syndrome characterized by thrombocytopenia, hemolytic anemia,
and liver dysfunction believed to result from microvascular endothelial
activation and cell injury.
The pathophysiology of HELLP syndrome is ill-defined. Some theorize that,
because HELLP is a variant of preeclampsia, the pathophysiology stems from
a common source. In preeclampsia, defective placental vascular remodeling
during weeks 16-22 of pregnancy with the second wave of trophoblastic
invasion into the decidua results in inadequate placental perfusion. The
hypoxic placenta then releases various placental factors such as soluble
vascular endothelial growth factor receptor-1 (sVEGFR-1), which then binds
vascular endothelial growth factor (VEGF) and placental growth factor (PGF),
causing endothelial cell and placental dysfunction by preventing them from
binding endothelial cell receptors. The result is hypertension, proteinuria,
and increased platelet activation and aggregation.
Furthermore, activation of the coagulation cascade causes consumption of
platelets due to adhesion onto a damaged and activated endothelium, in
addition to microangiopathic hemolysis caused by shearing of erythrocytes
as they traverse through capillaries laden with platelet-fibrin deposits.
Multiorgan microvascular injury and hepatic necrosis causing liver
dysfunction contribute to the development of HELLP. [1, 4, 5, 6, 7]
A study by Weiner et al reported that although severe preeclampsia and
HELLP syndrome have similar placental histopathologic findings, HELLP
syndrome was associated with higher rates of placental maternal vascular
supply lesions and small-for-gestational-age. [8] In addition, a review by
Stojanovska and Zenclussen noted that the HELLP syndrome is associated
with hypertension and/or proteinuria in only 80% of patients and exhibits
different cytokine activation. [9]
Another hypothesis proposes acute maternal immune rejection due to
immunocompetent maternal cells coming into contact with a genetically
distinct fetus, altering the maternal-fetal immune balance and causing
endothelial dysfunction, platelet activation and aggregation, and arterial
hypertension. [10]
Other theories include inborn errors of fatty acid oxidative metabolism
secondary to long- and medium-chain fatty acid mutations, which cause liver
damage secondary to insufficient mitochondrial oxidation of fatty acids
required for ketogenesis. [11, 12]
Yet another theory suggests a placental-instigated acute inflammatory
condition targeting the liver. [13]
In addition, dysfunction in the complement system via excessive activation
or defective regulation for a given amount of endothelial injury has been
proposed to cause damage to hepatic vessels in HELLP. [14]
Many hypotheses attempt to define the pathogenesis of HELLP syndrome,
but the true pathology remains a mystery.

Etiology
The cause of HELLP syndrome is currently unknown, although theories as
described in Pathophysiology have been proposed.
Risk factors for HELLP syndrome include the following:
 Maternal age older than 34 years
 Multiparity
 White race or European descent
 History of poor pregnancy outcome [1]
Prognosis
Most patients with HELLP syndrome stabilize within 24-48 hours, with the
most protracted postpartum recovery time in patients with class 1 disease. [2]
The recurrence rate is 2-27% in subsequent pregnancies. [17, 18]
Patients are at increased risk of preeclampsia or pregnancy-induced
hypertension, in addition to preterm delivery, fetal growth restriction,
and placental abruption in future pregnancies. [2, 17]
Women with HELLP syndrome are also at increased risk of developing
hypertension and cardiovascular disease. [6]
Maternal morbidity/mortality
Maternal mortality ranges from 1-3%, with a perinatal mortality rate of
35%. [19] Class 1 or complete HELLP (see Stages) is associated with the
highest incidence of perinatal morbidity and mortality. Sixty percent of
deaths occur in patients with class 1 disease; cerebral hemorrhage is the
most common autopsy finding. [20] Morbidity includes the following:
 Disseminated intravascular coagulation (DIC) (20%)
 Placental abruption (16%)
 Acute renal failure (7%)
 Pulmonary edema (6%) [19]
Neonatal morbidity/mortality
Fetal morbidity and mortality rates range from 9-24% [21] and usually result
from placental abruption, intrauterine asphyxia, or prematurity. [22]
Complications
Maternal complications
Maternal complications of HELLP syndrome may include the following:
 Hematologic: DIC, bleeding, hematoma
 Cardiac: Cardiac arrest, myocardial ischemia
 Pulmonary: Pulmonary edema, respiratory failure, pulmonary
embolism, adult respiratory distress syndrome (ARDS)
 CNS: Hemorrhage/stroke, cerebral edema, central venous thrombosis,
seizures, retinal detachment
 Renal: Acute renal failure, chronic renal failure requiring dialysis
 Hepatic: Hepatic (usually subcapsular) hematoma with possible
rupture, [23, 24] ascites, nephrogenic diabetes insipidus
 Infection [15]
A systematic review by Mossayebi et al, which included 58 pregnancies with
HELLP syndrome developing at less than 23 weeks’ gestation, reported
maternal complications in 45% of cases; the most frequent were hepatic,
central nervous system (CNS)–related, and respiratory. [25]
Neonatal complications
Neonatal complications of HELLP syndrome may include the following:
 Prematurity
 Intrauterine growth retardation (39%) [2]
 Thrombocytopenia (one third of neonates born to patients with HELLP;
4% of these infants will have intraventricular hemorrhage [22] )
References
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