Sx De HELLP

INTRODUCTION — HELLP is an acronym that refers to a syndrome characterized by Hemolysis with a microangiopathic blood smear, Elevated Liver enzymes, and a Low Platelet count [1]. It probably represents a severe form of preeclampsia (table 1 and table 2), but the relationship between the two disorders remains controversial. As many as 15 to 20 percent of patients with HELLP syndrome do not have antecedent hypertension or proteinuria, leading some authorities to believe that HELLP is a separate disorder from preeclampsia [2-4]. Both severe preeclampsia and HELLP syndrome may be associated with serious hepatic manifestations, including infarction, hemorrhage, and rupture.

This topic will focus upon the clinical manifestations, diagnosis, and management of HELLP syndrome. Preeclampsia is reviewed in detail separately. (See "Preeclampsia: Clinical features and diagnosis" and "Preeclampsia: Management and prognosis".)

INCIDENCE — HELLP develops in approximately 0.1 to 0.8 percent of pregnancies overall and in 10 to 20 percent of women with severe preeclampsia/eclampsia.

RISK FACTORS — A previous history of preeclampsia or HELLP is a risk factor for HELLP syndrome (see 'Recurrence in subsequent pregnancies' below). Sisters and offspring of women with a history of HELLP syndrome are also at increased risk of developing the syndrome [5]. A variety of genetic variants associated with an increased risk of HELLP syndrome have been reported, but have no role in clinical management [6].

In contrast to preeclampsia, nulliparity is not a risk factor for HELLP syndrome [7]. Half or more of affected patients are multiparous.

PATHOGENESIS — The pathogenesis of HELLP syndrome is unclear. If it is a form of severe preeclampsia, it likely originates from aberrant placental development and function. (See "Pathogenesis of preeclampsia".) As an independent entity, it has been attributed to abnormal placentation, similar to preeclampsia, but with greater hepatic inflammation and greater activation of the coagulation system than in preeclampsia [6,8,9]. In a case report of a woman with severe early HELLP syndrome, treatment with eculizumab, a targeted inhibitor of complement protein C5, was associated with marked clinical improvement and complete normalization of lab parameters for 16 days [10]. The authors chose this intervention based on the hypothesis that preeclampsia/HELLP is a systemic inflammatory disorder and the complement cascade is a key mediator, and the observation that women with mutations in complement regulatory proteins appear to be at increased risk of severe preeclampsia [11].

In less than 2 percent of patients with HELLP, the underlying etiology appears to be related to fetal long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency [12,13]. In one case series, all six pregnancies with fetal LCHAD deficiency developed severe maternal liver disease (HELLP or acute fatty liver of pregnancy [AFLP]) [14]. These complications probably were not due to chance or maternal heterozygosity for LCHAD deficiency alone because three other pregnancies with unaffected fetuses among these mothers were uncomplicated. In another case series in which 19 fetuses had LCHAD deficiency, 15 mothers (79 percent) developed AFLP or the HELLP syndrome during their pregnancies [15]. (See "Acute fatty liver of pregnancy".)

PATIENT PRESENTATION — HELLP syndrome has a variable presentation (table 3). The most common symptom is abdominal pain and tenderness in the midepigastrium, right upper quadrant, or below the sternum [16]. Many patients also have nausea, vomiting, and malaise, which may be mistaken for a nonspecific viral illness or viral hepatitis, particularly if the serum aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) are markedly elevated [17]. Less common signs and symptoms include headache, visual changes, jaundice, and ascites. Mistaking abdominal pain, nausea, vomiting, and malaise for viral illness is a common pitfall that has resulted in maternal death or severe morbidity [18].

Hypertension (blood pressure ≥140/90 mmHg) and proteinuria are present in approximately 85 percent of cases, but it is important to remember that either or both may be absent in women with otherwise severe HELLP syndrome [19].

Signs and symptoms typically develop between 28 and 36 weeks of gestation, but second trimester or postpartum onset is also common. In an illustrative series of 437 women who had 442 pregnancies complicated by the HELLP syndrome, 70 percent occurred prior to delivery [16]. Of these patients, approximately 80 percent were diagnosed prior to 37 weeks of gestation and fewer than 3 percent developed the disease between 17 and 20 weeks of gestation. The disease presented postpartum in 30 percent, usually within 48 hours of delivery, but occasionally as long as 7 days after birth. Only 20 percent of postpartum patients with HELLP had evidence of preeclampsia antepartum.

Serious maternal morbidity may be present at initial presentation or develop shortly thereafter. This includes disseminated intravascular coagulation (DIC), abruptio placentae, acute renal failure, pulmonary edema, subcapsular or intraparenchymal liver hematoma, and retinal detachment (see 'Maternal outcome' below) [16].

Bleeding related to thrombocytopenia is an unusual presentation.

DIAGNOSIS — The diagnosis of HELLP syndrome is based upon the presence of all of the laboratory abnormalities comprising its name (hemolysis with a microangiopathic blood smear, elevated liver enzymes, and low platelet count) in a pregnant woman. Thus, laboratory work-up should include [19]:

●Complete blood count with platelet count

●Peripheral smear

●Aspartate aminotransferase (AST), bilirubin

In addition, we obtain a serum creatinine concentration and urine protein to creatinine ratio.

We suggest obtaining these laboratory tests in women with new onset hypertension and/or characteristic symptoms (right upper quadrant/epigastric pain, nausea, vomiting, fatigue or malaise) in the second half of pregnancy or first postpartum week.

Pregnant/postpartum women who have some of the typical laboratory abnormalities but do not meet all of the laboratory criteria described below are considered to have partial HELLP syndrome [7].

Laboratory criteria — Precise criteria for HELLP are necessary for research purposes and for predicting maternal complications. We require the presence of all of the following criteria to diagnose HELLP (Tennessee classification) [16]:

●Microangiopathic hemolytic anemia with characteristic schistocytes (also called helmet cells) on blood smear (picture 1). Other signs suggestive of hemolysis include an elevated indirect bilirubin level and a low serum haptoglobin

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