HELLP Syndrome: Recognition

and Perinatal Management

MAUREEN O'HARA PADDEN, LCDR, MC, USN

! Am Fam Physician. 1999;60(3):829-836

" See related patient information handout on HELLP syndrome
(https://www.aafp.org/afp/1999/0901/p839.html), written by the author of this
article.

HELLP, a syndrome characterized by hemolysis, elevated liver enzyme

levels and a low platelet count, is an obstetric complication that is
frequently misdiagnosed at initial presentation. Many investigators
consider the syndrome to be a variant of preeclampsia, but it may be a
separate entity. The pathogenesis of HELLP syndrome remains unclear.
Early diagnosis is critical because the morbidity and mortality rates
associated with the syndrome have been reported to be as high as 25
percent. Platelet count appears to be the most reliable indicator of the
presence of HELLP syndrome. The D-dimer test may be a useful tool for
the early identification of patients with preeclampsia who may develop
severe HELLP syndrome. The mainstay of therapy is supportive
management, including seizure prophylaxis and blood pressure control
in patients with hypertension. Women remote from term should be
considered for conservative management, whereas those at term should
be delivered. Some patients require transfusion of blood products, and
most benefit from corticosteroid therapy. Rarely, patients with refractory
HELLP syndrome require plasmapheresis.
The acronym HELLP was coined in 1982 to describe a syndrome consisting of
hemolysis, elevated liver enzyme levels and low platelet count.1 The syndrome has
been considered a variant of preeclampsia, but it can occur on its own or in
association with preeclampsia. Pregnancy-induced hypertension, preeclampsia and
HELLP syndrome are related and overlap in their presentations. Because of the
serious associated morbidity and mortality, family physicians who provide
maternity care need to be aware of HELLP syndrome so that they can identify it
early.

Etiology and Pathogenesis

The pathogenesis of HELLP syndrome is not well understood. The findings of this
multisystem disease are attributed to abnormal vascular tone, vasospasm and
coagulation defects.2 To date, no common precipitating factor has been found. The
syndrome seems to be the final manifestation of some insult that leads to
microvascular endothelial damage and intravascular platelet activation. With
platelet activation, thromboxane A and serotonin are released, causing vasospasm,
platelet agglutination and aggregation, and further endothelial damage.2 Thus
begins a cascade that is only terminated with delivery.

The hemolysis in HELLP syndrome is a microangiopathic hemolytic anemia. Red

blood cells become fragmented as they pass through small blood vessels with
endothelial damage and fibrin deposits. The peripheral smear may reveal
spherocytes, schistocytes, triangular cells and burr cells. The elevated liver enzyme
levels in the syndrome are thought to be secondary to obstruction of hepatic blood
flow by fibrin deposits in the sinusoids. This obstruction leads to periportal necrosis
and, in severe cases, intrahepatic hemorrhage, subcapsular hematoma formation
or hepatic rupture. The thrombocytopenia has been attributed to increased
consumption and/or destruction of platelets.

Although some investigators speculate that disseminated intravascular

 coagulopathy (DIC) is the primary process in HELLP syndrome, most patients show
no abnormalities on coagulation studies. Patients who develop DIC generally do so
in the setting of well-developed HELLP syndrome. All patients with HELLP
syndrome may have an underlying coagulopathy that is usually undetectable.

Epidemiology and Risk Factors

HELLP syndrome occurs in approximately 0.2 to 0.6 percent of all pregnancies.3 In
comparison, preeclampsia occurs in 5 to 7 percent of pregnancies.3 Superimposed
HELLP syndrome develops in 4 to 12 percent of women with preeclampsia or
eclampsia.3 When preeclampsia is not present, diagnosis of the syndrome is often
delayed.4

The risk factors for HELLP syndrome differ from those associated with
preeclampsia (Table 1). The syndrome generally presents in the third trimester of
pregnancy, although it occurs at less than 27 weeks of gestation in an estimated 11
percent of patients.5 The syndrome presents antepartum in 69 percent of patients
and postpartum in 31 percent of patients.2 With postpartum presentation, the
onset is typically within the first 48 hours after delivery; however, signs and
symptoms may not become apparent until as long as seven days after delivery.

TABLE 1

Comparison of Risk Factors for HELLP Syndrome and

Preeclampsia

HELLP syndrome Preeclampsia

Multiparous Nulliparous

Maternal age greater than 25 Maternal age less than 20 years or greater than
years 45 years
:
 White race Family history of preeclampsia

History of poor pregnancy

Minimal prenatal care
outcome

Diabetes mellitus

Chronic hypertension

Multiple gestation

HELLP = hemolysis, elevated liver enzyme levels and low platelet count.

Clinical Presentation
The vague nature of the presenting complaints can make the diagnosis of HELLP
syndrome frustrating to physicians. Approximately 90 percent of patients present
with generalized malaise, 65 percent with epigastric pain, 30 percent with nausea
and vomiting, and 31 percent with headache.3 Because early diagnosis of this
syndrome is critical, any pregnant woman who presents with malaise or a viral-type
illness in the third trimester should be evaluated with a complete blood cell count
and liver function tests.6

The physical examination may be normal in patients with HELLP syndrome.

However, right upper quadrant tenderness is present in as many as 90 percent of
affected women.2 Edema is not a useful marker because swelling is a factor in up
to 30 percent of normal pregnancies.3 Hypertension and proteinuria may be absent
or mild. The differential diagnosis of HELLP syndrome includes acute fatty liver of
pregnancy, thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

Because of the variable nature of the clinical presentation, the diagnosis of HELLP
syndrome is generally delayed for an average of eight days.7 Many woman with this
syndrome are initially misdiagnosed with other disorders, such as cholecystitis,
esophagitis, gastritis, hepatitis or idiopathic thrombocytopenia.3 In one
:
 retrospective chart review of patients with HELLP syndrome, only two of 14
patients entered the hospital with the correct diagnosis.7

Diagnostic Tests
The three chief abnormalities found in HELLP syndrome are hemolysis, elevated
liver enzyme levels and a low platelet count. The hematocrit may be decreased or
normal and is typically the last of the three abnormalities to appear. The finding of a
decreased serum haptoglobin level may confirm ongoing hemolysis when the
hematocrit is normal.8 The serum transaminase levels may be elevated to as high
as 4,000 U per L, but milder elevations are typical. Platelet counts can drop to as
low as 6,000 per mm3 (6 × 109 per L), but any platelet count less than 150 per mm3
(150 × 109 per L) warrants attention. Unless DIC is present, the prothrombin time,
partial thromboplastin time and fibrinogen level are normal in patients with HELLP
syndrome. In a patient with a plasma fibrinogen level of less than 300 mg per dL (3
g per L), DIC should be suspected, especially if other laboratory abnormalities are
also present.

Proteinuria and an increased uric acid concentration are useful in diagnosing

preeclampsia but not HELLP syndrome.9 The platelet count is the best indicator of
the latter. Therefore, HELLP syndrome should be suspected in any patient who
shows a significant drop in the platelet count during the antenatal period.10 A
positive D-dimer test in the setting of preeclampsia has recently been reported to
be predictive of patients who will develop HELLP syndrome.11 The D-dimer is a
more sensitive indicator of subclinical coagulopathy and may be positive before
coagulation studies are abnormal.

Classification
:
 Two classification systems are used for HELLP syndrome. The first is based on the
number of abnormalities that are present. In this system, patients are classified as
having partial HELLP syndrome (one or two abnormalities) or full HELLP syndrome
(all three abnormalities). Women with full HELLP syndrome are at higher risk for
complications, including DIC, than women with the partial syndrome. Consequently,
patients with the full syndrome should be considered for delivery within 48 hours,
whereas those with partial HELLP syndrome may be candidates for more
conservative management.12

Alternatively, HELLP syndrome can be classified on the basis of platelet count

nadir: class I, less than 50,000 per mm3 (50 × 109 per L); class II, 50,000 to less
than 100,000 per mm3 (50 to 100 × 109 per L); and class III, 100,000 to 150,000 per
mm3 (100 to 150 × 109 per L).13 Patients with class I HELLP syndrome are at higher
risk for maternal morbidity and mortality than patients with class 2 or 3 HELLP
syndrome.5

Management
Once the diagnosis of HELLP syndrome has been established, the best markers to
follow are the maternal lactate dehydrogenase level and the maternal platelet
count.14 Laboratory abnormalities typically worsen after delivery and peak at 24 to
48 hours postpartum.14 The peak lactate dehydrogenase level signals the
beginning of recovery and subsequent normalization of the platelet count.14 The
platelet count nadir is somewhat predictive for hemorrhagic complications. The
incidence of hemorrhagic complications is higher when platelet counts are less
than 40,000 per mm3 (40 × 109 per L).15 However, hepatic imaging and liver biopsy
have shown that laboratory abnormalities do not correlate with the severity of
HELLP syndrome.16,17 Therefore, patients with HELLP syndrome who complain of
severe right upper quadrant pain, neck pain or shoulder pain should be considered
for hepatic imaging regardless of the severity of the laboratory abnormalities, to
assess for subcapsular hematoma or rupture.17
:
 Prompt recognition of HELLP syndrome and timely initiation of therapy are vital to
ensure the best outcome for mother and fetus. When the syndrome was first
described, prompt delivery was recommended.1 Recent research suggests that
morbidity and mortality do not increase when patients with HELLP are treated
conservatively.18 The treatment approach should be based on the estimated
gestational age and the condition of the mother and fetus (Figure 1).19

FIGURE 1.

Management of HELLP Syndrome*

Suggested approach to the management of patients with HELLP syndrome. (HELLP =

hemolysis, elevated liver enzyme levels and low platelet count; EGA = estimated gestational
age)
:
 Adapted with permission from Sibai BM, Frangieh AY. Management of severe preeclampsia.
Curr Opin Obstet Gynecol 1996;8:110–3.

Patients with HELLP syndrome may be eligible for conservative management if

hypertension is controlled at less than 160/110 mm Hg, oliguria responds to fluid
management and elevated liver function values are not associated with right upper
quadrant or epigastric pain. One study20 found that pregnancy was prolonged by an
average of 15 days when conservative management (i.e., bed rest, fluids and close
observation) was used in patients who were at less than 32 weeks of gestation.
Maternal morbidity was not increased. For infants, the prolongation of pregnancy
translated into less time in the neonatal intensive care unit, a decreased incidence
of necrotizing enterocolitis and a decreased incidence of respiratory distress
syndrome.20 Women treated conservatively should be managed in a tertiary care
center that has a neonatal intensive care unit and a perinatologist available for
consultation.

In the past, delivery in patients with HELLP syndrome was routinely accomplished
by cesarean section. Patients with severe HELLP syndrome, superimposed DIC or a
gestation of less than 32 weeks should be delivered by cesarean section. A trial of
labor is appropriate in patients with mild to moderate HELLP syndrome who are
stable, have a favorable cervix and are at 32 weeks of gestation or greater.2

Patients with HELLP syndrome should be routinely treated with corticosteroids.

The antenatal administration of dexamethasone (Decadron) in a high dosage of 10
mg intravenously every 12 hours has been shown to markedly improve the
laboratory abnormalities associated with HELLP syndrome.21 Patients treated with
dexamethasone exhibit longer time to delivery; this facilitates maternal transfer to a
tertiary care center and postnatal maturity of fetal lungs.

Steroids given antenatally do not prevent the typical worsening of laboratory

abnormalities after delivery. However, laboratory abnormalities resolve more quickly
in patients who continue to receive steroids postpartum.10 Corticosteroid therapy
should be instituted in patients with HELLP syndrome who have a platelet count of

3 9
:
 less than 100,000 per mm3 (100 × 109 per L) and should be continued until liver
function abnormalities are resolving and the platelet count is greater than 100,000
per mm3 (100 × 109 per L).

Patients with HELLP syndrome should be treated prophylactically with magnesium

sulfate to prevent seizures, whether hypertension is present or not. A bolus of 4 to 6
g of magnesium sulfate as a 20 percent solution is given initially. This dose is
followed by a maintenance infusion of 2 g per hour. The infusion should be titrated
to urine output and magnesium level. Patients should be observed for signs and
symptoms of magnesium toxicity. If toxicity occurs, 10 to 20 mL of 10 percent
calcium gluconate should be given intravenously.

Antihypertensive therapy should be initiated if blood pressure is consistently

greater than 160/110 mm Hg despite the use of magnesium sulfate. This reduces
the risk of maternal cerebral hemorrhage, placental abruption and seizure. The goal
is to maintain diastolic blood pressure between 90 and 100 mm Hg. The most
commonly used antihypertensive agent has been hydralazine (Apresoline), which is
given intravenously in small incremental doses of 2.5 to 5 mg (with 5 mg as the
initial dose) every 15 to 20 minutes until the desired blood pressure is achieved.
Labetolol (Normodyne) and nifedipine (Procardia) have also been used with
success.

Because of reported potentiation of effect, care should be taken when nifedipine

and magnesium sulfate are given concurrently.22 Diuretics may compromise
placental perfusion and therefore are not used to control blood pressure in patients
with HELLP syndrome. A hypertensive crisis may be treated with a continuous
infusion of nitroglycerin or sodium nitroprusside (Nipride).

Between 38 and 93 percent of patients with HELLP syndrome receive some form of
blood product.15 Patients with a platelet count greater than 40,000 per mm3 (40 ×
109 per L) are unlikely to bleed. These patients do not require transfusion unless the
platelet count drops to less than 20,000 per mm3 (20 × 109 per L). Patients who
undergo cesarean section should be transfused if their platelet count is less than
50,000 per mm3 (50 × 109 per L). Prophylactic transfusion of platelets at delivery
:
 does not reduce the incidence of postpartum hemorrhage or hasten normalization
of the platelet count.15 Patients with DIC should be given fresh frozen plasma and
packed red blood cells.

The laboratory abnormalities in HELLP syndrome typically worsen after delivery

and then begin to resolve by three to four days postpartum.14 Plasmapheresis has
been successful in patients with severe laboratory abnormalities (i.e., a platelet
count of less than 30,000 per mm3 [30 × 109 per L] and continued elevation of liver
function values) who have required repeat transfusions to maintain their
hematocrit at 72 hours postpartum. In these patients, plasmapheresis has resulted
in an increase in the platelet count and a decrease in the lactate dehydrogenase
level.23–25

ANESTHESIA CONSIDERATIONS

Pain relief with intravenous narcotics and local anesthesia is acceptable but
certainly not optimal for pain control. Epidural anesthesia has been controversial
but is the technique of choice when it can be accomplished safely.26 Insertion of an
epidural catheter is generally safe in patients with a platelet count greater than
100,000 per mm3 (100 × 109 per L), normal coagulation studies and a normal
bleeding time.26 General anesthesia can be used when regional anesthesia is
considered unsafe.

COMPLICATIONS

The mortality rate for women with HELLP syndrome is approximately 1.1 percent.5
From 1 to 25 percent of affected women develop serious complications such as
DIC, placental abruption, adult respiratory distress syndrome, hepatorenal failure,
pulmonary edema, subcapsular hematoma and hepatic rupture. A significant
percentage of patients receive blood products.5
:
 Infant morbidity and mortality rates range from 10 to 60 percent, depending on the
severity of maternal disease.3 Infants affected by HELLP syndrome are more likely
to experience intrauterine growth retardation and respiratory distress syndrome.27

Prognosis
Patients who have had HELLP syndrome should be counseled that they have a 19
to 27 percent risk of developing the syndrome in subsequent pregnancies.28 They
also have up to a 43 percent risk of developing preeclampsia in another
pregnancy.28 Patients with class I HELLP syndrome have the highest risk of
recurrence.28 When the syndrome recurs, it tends to develop later in gestation and
is generally less severe after two episodes. Patients who have had HELLP
syndrome may subsequently use oral contraceptive pills safely.29 Patients who
develop atypical early-onset preeclampsia or HELLP syndrome should be screened
for the presence of antiphospholipid antibodies.30

Much controversy surrounds the use of acetylsalicylic acid (aspirin) or calcium to

prevent preeclampsia. To date, neither calcium nor aspirin has been specifically
studied in patients with HELLP syndrome. Although one study suggested that
aspirin therapy might be helpful in selected patients with early-onset severe
preeclampsia,31 a large, double-blind, randomized, controlled trial failed to
demonstrate benefit for this approach.32 In this recently released large study,
aspirin therapy did not reduce the incidence of preeclampsia or improve perinatal
outcomes in pregnant women at high risk for this complication of pregnancy.32
Likewise, several studies suggested that calcium might be useful in preventing
preeclampsia in high-risk patients.33,34 Yet a recent large, multicenter study found
that calcium supplementation during pregnancy did not prevent preeclampsia or
adverse perinatal outcomes.35

Author Information
:
 MAUREEN O'HARA PADDEN, LCDR, MC, USN, is a family physician in the residency
teaching program at Naval Hospital, Camp Pendleton, Calif. Dr. Padden is a
graduate of the Uniformed Services University of the Health Sciences F. Edward
Hébert School of Medicine, Bethesda, Md. She completed a residency in family
medicine at Naval Hospital, Camp Pendleton.

The author thanks Everett Magann, M.D., of the University of Mississippi, Jackson, and
Richard Emerine, M.D., and Richard Leader, Naval Hospital, Camp Pendleton, Calif., for
critical review and recommendations in the preparation of the manuscript.

The opinions and assertions contained herein are the private views of the author and are
not to be construed as official or as reflecting the views of the U.S. Navy Medical
Department or the Naval service at large.

Address correspondence to Maureen O'Hara Padden, LCDR, MC, USN, Family Practice
Residency, Naval Hospital, Camp Pendleton, CA 92055. Reprints are not available from
the author.

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