Hemolysis, Elevated Liver Enzymes, and Low Platelet (HELLP) syndrome is a disease specific to pregnancy and is thought to be secondary to abnormal placentation in the first trimester. Recently, HELLP syndrome has shown to be a disease associated with the alternative pathway of complement (APC). Diseases of the APC especially atypical hemolytic uremic syndrome (aHUS) are highly morbid and phenotypically similar to HELLP syndrome as they both have hemolysis, renal injury, altered mental status, liver enzyme elevation, and thrombocytopenia. Instead of an origin of placental pathology, HELLP syndrome could be augmented by complement augmentation and thus a variant of aHUS. In fact, 20% of women diagnosed with aHUS have a pregnancy trigger, and similar germline mutations of the APC in HELLP are prevalent in both diseases. HELLP syndrome's current treatment involves blood pressure control, magnesium sulfate for seizure prophylaxis, fetal monitoring, and ultimately delivery after completion of betamethasone for fetal lung maturity. This often leads to iatrogenic preterm birth. With new data that HELLP syndrome is a disease of the APC, exploring complement inhibition with eculizumab (ECU) is warranted as it is the standard treatment in aHUS. If HELLP syndrome is truly a disease of the APC, ECU should be effective in halting, slowing, and/or reversing disease process. Treatment could hopefully lead to a decrease in maternal morbidity and safe latency of pregnancy beyond 48 hours after betamethasone completion.
The present study is an open label clinical trial of eculizumab administration to women with HELLP syndrome at 23-29 6/7 weeks gestation. We hypothesize that women who receive ECU will have an improvement in lab values, less maternal morbidity, and a longer latency of pregnancy when compared to historic controls (women not given ECU).
The initial steps in management of HELLP patients are to assess the mother, stabilize women who are unstable, and assess fetal status (nonstress test and ultrasound examination for biophysical profile and fetal presentation).
Because of the potential for severe maternal complications, which can develop rapidly, women with HELLP should be managed at a tertiary care center with appropriate levels of maternal and neonatal intensive care.
The cornerstone of therapy for HELLP occurring during pregnancy is delivery, which is the only effective treatment. This often leads to iatrogenic preterm birth.
There is consensus among experts that prompt delivery is indicated after maternal stabilization for any of the following :
- Pregnancies after 34 weeks of gestation.
- Pregnancies that have not reached a stage of fetal maturity that ensures a reasonable chance of extrauterine survival.
- Fetal demise.
- Abruptio placentae.
In the absence of any of these three scenarios or the urgent clinical scenarios described above, delivery may be delayed until a course of corticosteroids has been administered and completed (eg, 48 hours after the first injection of betamethasone).
Magnesium sulfate is given intravenously to patients on the labor and delivery unit to prevent convulsions and for fetal/neonatal neuroprotection in pregnancies between 24 and 32 weeks of gestation with a live fetus.
With new data that HELLP syndrome is a disease of the APC, exploring complement inhibition with eculizumab (ECU) is warranted as it is the standard treatment in aHUS. If HELLP syndrome is truly a disease of the APC, ECU should be effective in halting, slowing, and/or reversing disease process.
Treatment could hopefully lead to a decrease in maternal morbidity and safe latency of pregnancy beyond 48 hours after betamethasone completion and could become the gold standard for the management of HELLP syndrome.