Results
In this study 54 patients were prospectively enrolled. 48 women were
diagnosed with HELLP syndrome while six women fulfilled six or more
Swansea criteria and therefore were diagnosed with AFLP. The clinical
characteristics of the study population are depicted in Table 1.
AFLP patients showed impressively high sFlt-1 levels up to 147170pg/ml
(median: 57570pg/ml [range: 31609-147170pg/ml]) which were
significantly higher than those found in patients with HELLP syndrome
(9713pg/ml [1348-30781]pg/ml; p<0.001; Figure 1).
PLGF serum levels were higher in patients with AFLP than in those with
HELLP syndrome (median: 197 pg/ml [range 127-487pg/ml] versus 40
pg/ml [9-644pg/ml], p<0.01; Figure 2).
sFlt-1/PLGF-ratios were not significantly different between AFLP and
HELLP syndrome patients (192 [157-1159] versus 232 [3-948]; NS);
(Figure 3).
ROC analysis was performed to assess the test performance of sFlt-1 and
PLGF in discriminating between AFLP and HELLP syndrome. A sFlt-1 cut-off
value of 31.2 ng/ml allowed differentiating between these two diseases
with a sensitivity and specificity of 100%. For PLGF on the other hand
the area under the ROC curve was 0.89 (95%CI 0.79-0.98;
p<0.005). A PLGF cut-off value of 110 g/ml showed a
sensitivity of 100% with a specificity of 81 % in distinguishing
between AFLP and HELLP syndrome.
To correct for a potential gestational age-dependent bias regarding the
angiogenic parameters patients with AFLP and HELLP syndrome were matched
(±1 week) on a 1:2 basis. Compared to gestational age-matched HELLP
syndrome patients median [range] sFlt-1 serum levels were still
higher in AFLP patients (HELLP: 9209 pg/ml [2544-30781] versus AFLP:
57570 pg/ml [range: 31609-147170pg/ml]; p<0.001).
Similarly, median PLGF serum concentrations were higher in AFLP patients
when compared to women affected by HELLP syndrome; (AFLP: 197pg/ml
[127-487pg/ml; n=6] versus HELLP: 57pg/ml [17-232 pg/ml; n=12],
p<0.01). Since serum levels of both sFlt-1 and PLGF were
elevated in patients with AFLP when compared with those affected by
HELLP syndrome sFlt-1/PLGF-ratio were not significantly different
between AFLP and HELLP syndrome patients (AFLP: 192 [157-1159]
versus HELLP: 202 [17-832], respectively, p=NS). There was no
overlap in sFlt-1 serum concentrations between theses matched groups, a
sFlt-1 cut-off value of 31100 pg/ml differentiated perfectly between the
two pregnancy complications.
Three out of six patients (50%) in the AFLP group showed sFlt-1 levels
over the threshold of the test detection limit of 85.0 ng/ml. Performing
dilution series with human serum 1:10, sFlt-1 levels up to 147170 pg/ml
were detected.
Further analysis showed that no FGR was found in the off-springs of our
AFLP cohort, whereas 48% of all off-springs following pregnancies
affected by HELLP syndrome were considered as FGR. (Table 1)The rate of
NICU admission was comparable between neonates following pregnancies
with AFLP and HELLP syndrome, however AFLP off-springs showed
significantly lower umbilical cord artery pH values than their peers
following HELLP syndrome: AFLP: 7.23 (7.11-7.28 versus HELLP: 7.33
(7.12-7.38; p<0.01). Apgar scores as well as maternal age or
BMI did not differ significantly between the two groups although 50% of
the neonates in the AFLP group had an Apgar score at 5 minutes of
<7.0 No significant difference was found in aminotransferases
concentrations between women affected by HELLP syndrome and AFLP.