The course of angiogenic factors in early- vs. late-onset preeclampsia and HELLP syndrome

Abstract

Aims Preeclampsia (PE) is considered a uniformly progressive disease, however, it shows a different pattern of clinical progression in patients with early (<34 weeks) or late (≥34 weeks) onset of the disease. Angiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) are closely related to the clinical course of PE. We evaluated sFlt-1 and PlGF levels in the clinical course of PE in women admitted with a diagnosis of PE at different gestational ages. Methods This retrospective study included 34 patients with PE, of which 11 patients had HELLP syndrome (over a period of 3 years). Serial measurements of sFlt-1 and PlGF were completed from admission until delivery. Values are presented as mean±standard deviation. Results Mean gestational age of admission among women with early onset PE was significantly lower, at 29±3 weeks compared to 37±1 weeks among patients with late onset disease. Mean prolongation of pregnancy was 6 days, which was similar within the two groups. Compared to women with late onset PE, women with early-onset PE had a greater increase in sFlt-1 (11% vs. 3% per day, P<0.05), greater decrease in PlGF levels (21% vs. 10% per day, P=0.30), resulting in a much higher increase in sFlt-1/PlGF ratio (23% vs. 8% per day, P<0.05). Patients with HELLP syndrome showed comparable progression patterns. Conclusion In a similar way to the progressively worsening clinical course observed in women with early onset PE, there were changes in the angiogenic profile that leads to a more anti-angiogenic state in these women with each passing day. These findings may have implications in identification of the women for appropriate patient management and possible future therapies based on the reduction of sFlt-1 levels.

Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in Preeclampsia

“…5,13,23,[35][36][37] In some women there appeared to be a rebound following apheresis (see Figures 2, 4, and 5). Given that the volume of distribution of sFlt-1 is large, with significant quantities bound to the interstitial matrix and ,20% of total body sFlt-1 circulating, 38 rebound following equilibration with the interstitial matrix compartment is not surprising.…”

“…This may be facilitated by ensuring similar baseline sFlt-1/PlGF ratios, which have robust diagnostic and prognostic performances. [35][36][37] Short-term neonatal outcomes of preterm infants born to treated women compared with untreated women with preeclampsia and to infants born preterm for reasons other than preeclampsia were similar, except that neonates born to treated women required fewer days on supplementary oxygen; no infants died. The similar Apgar scores, umbilical cord blood pHs, and estimated biologic risks suggest that apheresis did not influence fetal circulation or mechanisms of neonatal adaptation.…”

“…We conducted the study at two sites in Germany (Cologne and Leipzig) where testing for blood concentrations of sFlt-1 and PlGF is available for routine prenatal care measures. 36 The study conduct adhered to the Declaration of Helsinki, with ethics approval of the Massachusetts General Hospital and the University of Cologne/ University of Leipzig. Each patient signed written informed consent before any study procedures.…”

Update on the Diagnosis and Prognosis of Preeclampsia with the Aid of the sFlt-1/ PlGF Ratio in Singleton Pregnancies

“…On the contrary, very high sFlt-1/PlGF ratios [27] as well as their rapid increase in serial measurements [30,31] are closely related with the imminent onset of PDrelated complications, and this tool has the unique property of being inversely correlated with the time remaining until delivery is indicated. Before 34 weeks (when objective parameters such as the sFlt-1/PlGF ratio may be of greatest interest for guiding management), it was shown that when the sFlt-1/PlGF ratio was >38, the remaining time to delivery was 38% shorter than in women with an sFlt-1/PlGF ratio of ≤38 [32].…”

Preeclampsia and Vascular Function: A Window to Future Cardiovascular Disease Risk

“…A study comparing angiogenic factors in early-and late-onset preeclampsia found that while the sFlt-1 concentration and sFlt-1/PlGF ratio increased for all cases from diagnosis to time of delivery, the increase was much higher for early-onset preeclampsia (SFlt-1: 11% vs. 3% per day, p < 0.05, and sFlt-1/PlGF ratio: 23% vs. 8% per day, p < 0.05). 63 Noninvasive arterial tonometry may also be useful for identifying women who are at risk for preeclampsia. AIx75 and PWV readings, for example, have provided evidence of arterial stiffness at the 11-to 13-week mark in women who subsequently develop preeclampsia.…”