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. [4, 1, 5, 5, 6, 7, 8, 9]
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. [10] 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. [11]
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. [12]
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. [13, 14]
Yet another theory suggests a placental-instigated acute inflammatory condition targeting the liver. [15]
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. [16]
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
Epidemiology
HELLP syndrome occurs in 0.1%-0.6% of all pregnancies and in 4%-12% of patients with preeclampsia. HELLP syndrome typically occurs between week 27 of gestation and delivery, or immediately postpartum in 15%-30% of cases. [18, 19, 20, 21]
The incidence of HELLP syndrome is significantly higher in whites and women of European descent. [20]
HELLP has been shown to occur in older maternal age groups, with a mean age of 25 years. In contrast, preeclampsia is most common in younger patients (mean age, 19 years). [20]
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. [22, 23]
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. [22, 2]
Women with HELLP syndrome are also at increased risk of developing hypertension and cardiovascular disease. [7]
Maternal morbidity/mortality
Maternal mortality ranges from 1%-3%, with a perinatal mortality rate of 35%. [24] 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. [25, 26] Morbidity includes the following:
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Disseminated intravascular coagulation (DIC) (20%)
-
Placental abruption (16%)
-
Acute renal failure (7%)
-
Pulmonary edema (6%) [24]
Neonatal morbidity/mortality
Fetal morbidity and mortality rates range from 9%-24% [27] and usually result from placental abruption, intrauterine asphyxia, or prematurity. [28]
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, [29] ascites, nephrogenic diabetes insipidus
Neonatal complications of HELLP syndrome may include the following:
-
Overview of the Management of HELLP Syndrome
Tables
|
Class 1 (Severe) |
Class 2 (Moderate) |
Class 3 (Mild) |
Platelets |
≤50,000/µL |
50,000-100,000/µL |
100,000-150,000/µL |
AST or ALT |
≥70 IU/L |
≥70 IU/L |
≥40 IU/L |
LDH |
≥600 IU/L |
≥600 IU/L |
≥600 IU/L |
Incidence of bleeding |
13% |
8% |
No increased risk |
Laboratory Test |
Possible Result |
Cause |
Recovery to Baseline (in Number of Hours or Days Postpartum) |
Haptoglobin |
↓ |
Hemolysis |
24-30 hours |
LDH |
↑ |
Hemolysis or liver dysfunction |
3-5 days |
AST or ALT |
↑ |
Liver dysfunction |
3-5 days |
Bilirubin |
↑ |
Hemolysis |
- |
Platelets (CBC) |
↓ |
Consumption |
6-11 days |
Hemoglobin/Hematocrit (CBC) |
↓ |
Hemolysis |
- |
PT |
Normal |
|
|
PTT |
↑ |
Liver dysfunction |
- |
D-dimer |
↑ |
Increased coagulation and secondary fibrinolysis |
- |
Fibrinogen |
↓ |
- |
