Elevated PlGF Levels Found with Acute Fatty Liver of Pregnancy

Although uncommon, with an estimated global incidence of 1 in 7,000 to 15,000 pregnancies, AFLP is a life-threatening disease for both mother and child.

During preeclampsia, poor placentation triggers the excessive release of the soluble vascular endothelial growth factor receptors (VEGFR); also known as soluble Fms-like tyrosine kinase-1 (sFlt-1), which binds its free circulating ligands VEGF and placental growth factor (PlGF). The ensuing angiogenic imbalance is thought to contribute significantly to the clinical manifestations of this disorder.

Physicians at the Erasmus MC University Hospital (Rotterdam, the Netherlands) and their colleagues utilized human serum samples from a database of women with singleton pregnancies who had a clinical diagnosis of AFLP between 2005 and 2020. The team compared matched women with AFLP to 12 gestational age (GA) matched women with either no preeclampsia, confirmed preeclampsia, or HELLP syndrome, given that the values of sFlt-1, free, and total PlGF alter with advancing gestation.

Measurement of sFlt-1, Free PlGF, and Total PlGF was carried out. For the thermal dissociation of all sFlt-1-PlGF complexes, serum samples were placed in a heating block at 70 °C for 10 minutes. Measurements of sFlt-1 and PlGF before and after heating were performed using the automated Elecsys immunoassay from Roche Diagnostics (Cobas 6000, e-module; Rotterdam, the Netherlands).

The scientist found that median levels of free PlGF were significantly lower in 13 women with preeclampsia (117pg/mL) or in 12 women with hemolysis elevated liver enzymes and low platelet count syndrome (59 pg/mL) compared with 11 women without preeclampsia (349 pg/mL). In contrast, median total PlGF did not differ between women with no preeclampsia, preeclampsia, and hemolysis elevated liver enzymes and low platelet count syndrome (354 pg/mL versus 435 pg/mL versus 344 pg/mL) respectively, whereas it was markedly elevated in AFLP compared with all groups (2,054 pg/mL). Furthermore, in AFLP, both sFlt-1 and total PlGF declined rapidly post-delivery, with significantly higher in 12 pre-delivery total PlGF (median, 2,054 pg/mL) than 14 postpartum levels (median, 163 pg/mL), suggesting that in AFLP, PlGF is largely placenta-derived.

The authors concluded that their findings indicated that like sFlt-1, PlGF production is significantly upregulated in AFLP, mainly originating from the placenta. Importantly, total PlGF can now be easily calculated from already available free PlGF and sFlt-1 levels, allowing subsequent evaluation of other groups in whom PlGF is altered. The study was published on June 28, 2021in the journal Hypertension.

Related Links:
Erasmus MC University Hospital
Roche Diagnostics