Finally impaired endothelial integrity culminates
Finally, impaired endothelial integrity culminates in an increased plasma protein concentration in the interstitial space, and thus accumulation of fluid in the ECM, favoring the swelling of the face and limbs  mainly. Concurrently with this systemic change, there is intense activation of coagulation, reduced tissue perfusion, and increased synthesis of vasoconstrictor agents , .
Biomarkers and management of preeclampsia The complex etiopathogenesis of PE instigates worldwide research on the definition of clinical and laboratory parameters that allow for the early diagnosis of this entity. Because systemic melk inhibitor and proteinuria are not specific symptoms , different biomarkers have been investigated as promising diagnostic tools , , . In the first and second trimesters of pregnancy, the relationship between sFlt-1/PlGF is regarded as a promising index of the imbalance between angiogenic and antiangiogenic factors , , , . Serum levels of both factors are already altered in early pregnancy; for instance, sFlt-1 can be detected from the fifth week. When it is associated with changes in plasma concentration of sEng and with Doppler ultrasound of the uterine artery between 20th and 24th week, the predictive value of these factors reaches up to 89.5% sensitivity and 95% specificity , ; whereas in the presence of abnormal uterine perfusion there may be 100% sensitivity with 93.3% specificity . It is also suggested that nulliparous pregnant women who have serum levels of PlGF <107pg/ml or <20pg/ml on the 26th week are at risk of developing moderate and severe PE , respectively. In the third quarter, the change in PlGF levels, combined with maternal characteristics, has a sensitivity of 86% for the diagnosis of PE between the 34th and 37th weeks of pregnancy, and 53% from the 37th week; with 10% false positive results . Other studies point out that the combined assessment of sFlt-1 and PlGF has a sensitivity of 74.1–78%, with a specificity of 67.2–84% , , . Moreover, measurement of sFlt-1 and PlGF can contribute to the identification and interpretation of abnormal uterine artery Doppler ultrasound parameters in GA <34 weeks , . Pregnant women with increased rates of sFlt-1:PlGF are increasingly at risk of severe hypertensive disorders, placental rupture, inotropic support, and endotracheal intubation , , whereas women with high levels of sEng only present a serious risk of hematoma or hepatic rupture . A prospective observational study conducted in 14 countries, entitled PROGNOSIS (Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia Study), investigated the value of using the sFlt-1:PlGF ratio for prediction of preeclampsia in short term. The median sFlt-1:PlGF ratio was higher among pregnant women with PE or HELLP syndrome (146.4) within the first week or four weeks of evaluation (104.8), when compared to those who did not develop any disorder within the first week (6.3) or within four weeks (5.5). For the single-cutoff model (independent of gestational age; sFlt-1:PIGF ratio=38), the gestational phase model [a model with two cutoff points, one for the earlier gestational phase (24 to <34 weeks) and one for the later gestational phase (≥34 weeks)], and the gestational-week model (a model with a cutoff point for each gestational week), the area under the curve were 89.2%, 90.9%, and 90.5% for 1-week rule out and 86.4%, 86.2%, and 86.2% for 4-week rule in, respectively. Moreover, the median cutoff points were 38.2 (1-week rule out) and 37.5 (4-week rule in); indicating neurons the single cutoff point of 38 was suitable for validation . In validation phase, the median sFlt-1:PlGF ratio was 87.8 for pregnant women diagnosed with PE or HELLP syndrome within the first week of evaluation and 59.4 within four weeks, when compared to those who did not develop any disorder within the first week (8.0) and within four weeks (6.3). Negative predictive value (absence of diagnosis within 1 week) of 38 or lower for the sFlt-1:PlGF ratio was 99.3%, and the positive predictive value (diagnosis of PE, eclampsia or HELLP syndrome within 4 weeks) was 36.7%. Thus, the results suggest that the use of sFlt-1:PlGF ratio to evaluate proteinuria and blood pressure contributes to the diagnosis of PE .