Symptoms of HELLP not determined by time of onset

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A recent review evaluating early-onset hemolysis, elevated liver enzymes, and low platelets syndrome found signs and symptoms similar to those observed later in gestation.

Symptoms of HELLP not determined by time of onset | Image Credit: © Yakobchuk Olena - © Yakobchuk Olena - stock.adobe.com.

Symptoms of HELLP not determined by time of onset | Image Credit: © Yakobchuk Olena - © Yakobchuk Olena - stock.adobe.com.

Symptoms of hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome are similar between early-onset disease and disease later in gestation, according to a recent review published in the American Journal of Obstetrics & Gynecology.

Takeaways

  • Symptoms of HELLP syndrome, including hemolysis, elevated liver enzymes, and low platelets, are similar whether the condition occurs early or later in gestation.
  • HELLP syndrome is characterized by specific criteria, including lactate dehydrogenase levels, platelet count, and liver enzyme abnormalities.
  • Approximately 0.5% to 0.9% of pregnancies are affected by HELLP syndrome, and it's often associated with preeclampsia with severe features.
  • HELLP syndrome can lead to serious complications, with a maternal mortality rate of up to 24%, and early-onset cases are relatively rare.
  • In early-onset HELLP syndrome, antiphospholipid syndrome workup is recommended, and pregnancy outcomes are often challenging, with many cases resulting in fetal loss or neonatal complications.

HELLP syndrome is defined as an additional criterion for preeclampsia with severe features. Criteria for HELLP syndrome include lactate dehydrogenase (LDH) of 600 IU/L or more, platelet count under 100×109/L, and aspartate transaminase and alanine transaminase elevated over twice the regular upper limit.

Of pregnancies, 0.5% to 0.9% are impacted by HELLP syndrome, and 10% to 20% are impacted by preeclampsia with severe features. Symptoms of HELLP syndrome include right upper quadrant pain, general malaise, hypertension, nausea, vomiting, and proteinuria. 

A maternal mortality rate of up to 24% has been reported in patients with HELLP syndrome. Additionally, early-onset HELLP syndrome is rare, making little known about its presentation. Investigators conducted a systematic literature review to address this information gap.

Databases evaluated include PubMed, Ovid MEDLINE, Scopus, CINAHL Cochrane Library, and ClinicalTrials.gov. Literature from the databases’ inception until January 1, 2023, were eligible for inclusion. Unpublished studies, review articles, and abstracts were excluded from the analysis.

Search terms included “hemolysis, elevated liver enzymes, low platelets,” “hemolysis, elevated liver enzymes, low platelets syndrome,”“HELLP,” “HELLP syndrome,” “previable,” “periviable,” “pre-viable,” “peri-viable,”“first trimester,” “second trimester,” “<23 weeks,” “before 23 weeks,” “<23 weeks’ gestation,” and “before 23 weeks’ gestation.”

Literature search, study selection, and data extraction were completed by 2 reviewers independently. Data extracted included obstetrical and medical history, gestational age at symptom onset and diagnosis, laboratory workup, clinical presentation, and maternal and neonatal outcomes.

There were 46 studies included in the analysis, of which 41 were case reports and 5 were case series. Most had a moderate risk of bias, determined by criteria with domains including selection, ascertainment, causality, and reporting. Across the included studies, 55 patients with 58 total pregnancies met the inclusion criteria.

Participants were aged a mean 29.2±6.0 years, and 23 were primigravidas. Seven cases of chronic hypertension and 5 cases of preeclampsia or gestational hypertension were reported. 

HELLP syndrome symptom onset occurred between 13 and 23 weeks’ gestation, with the mean age of onset reported at 132 days. Of pregnancies with reported gestational age at diagnosis, 44% were diagnosed at 20 weeks’ gestation or later, while 36% were diagnosed before 20 weeks and 13% before 17 weeks.

Elevated blood pressure was the most common sign reported at presentation. Other common symptoms included abdominal pain, nausea, vomiting, headache, and edema. Of patients, 12% were normotensive at presentation and 16% never developed hypertension.

An LDH of 600 IU/L or greater was reported in 68% of cases, liver enzyme abnormalities in 94%, thrombocytopenia in 93%, platelet counts of 50×109/L or less in 50%, and proteinuria in 88%. A median duration from HELLP syndrome diagnosis to pregnancy outcomes of 0 days was reported, with delivery performed on the day of HELLP syndrome diagnosis in 46% of cases.

There were 21 continued pregnancies. Of these, living neonates were reported in 14%, early fetal death in 48%, stillbirth in 28%, and neonatal demise in 10%. Among the 3 living neonates, 2 were born by cesarean delivery and 1 by induction of labor. All 3 deliveries occurred in the twenty-third week of gestation.

These signs and symptoms among early-onset HELLP pregnancies were similar to those observed in later gestation. Investigators recommended antiphospholipid syndrome workup for early-onset HELLP syndrome.

Reference

Mossayebi MH, Iyer NS, McLaren RA, Moussa HN, Sibai BM, Al-Kouatly HB. HELLP syndrome at <23 weeks’ gestation: a systematic literature review. American Journal of Obstetrics & Gynecology. 2023;229(5):502-515.E10. doi:10.1016/j.ajog.2023.04.046

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