Evaluation of agreement of placental growth factor (PlGF) tests and the soluble FMS-like tyrosine kinase 1 (sFlt-1)/PlGF ratio, comparison of predictive accuracy for pre-eclampsia, and relation to uterine artery Doppler and response to aspirin

Abstract Background Preeclampsia is a leading hypertensive disorder in pregnant women. The angiogenic biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio, have been shown to be associated with diagnosis and prediction of preeclampsia. The objective of this study is to validate the analytical performance of sFlt-1 and PlGF on the Cobas e602 system (Roche Diagnostics Corporation). Method Intra-day and inter-day precisions for both sFlt-1 and PlGF assays were assessed using quality control materials provided from Roche Diagnostics. The accuracies for both assays were assessed by running 60 patient samples, which have been previously analyzed on the Elecsys 411 analyzer (Roche Diagnostics Corporation) at the Beth Israel Deaconess Medical Center. Linearity studies for both assays were performed using patient plasma spiked with recombinant sFlt-1 and PlGF proteins (R&D systems). Hemolysis, icterus, lipemia and biotin interference studies were performed by spiking hemolysate, bilirubin, intralipid or biotin into either pooled patient plasma with detectable levels of sFlt-1 and PlGF or otherwise, patient plasma spiked with recombinant sFlt-1 and PlGF proteins. Results Total precisions for both assays demonstrated CVs of <5.0%. The sFlt-1 and PlGF assays demonstrated analytical measuring ranges of 3060,000 pg/mL and 79,000 pg/mL, respectively (r2 > 0.98). Lower limit of quantitation (10% CV) was 30 pg/mL for sFlt-1 and 7 pg/mL for PlGF, respectively. Interference studies showed sFlt-1 and PlGF were not significantly affected by hemolysis up to H-indices of 500 and 1000 respectively; both assays were not affected by bilirubin up to an I-index of 60, and lipemia up to an L-index of 2800. Biotin at concentrations >30 ng/mL caused significant negative bias for both sFlt-1 and PlGF assays. Comparison studies showed the following: Cobas e602 sFLT-1 = 1.09 [Elecsys 411 sFLT-1] +203 (r2=0.97, Sy/x=1234, n=58); Cobas e602 PlGF = 1.10 [Elecsys 411 PlGF] +47 (r2=0.99, Sy/x=22.1, n=58); Cobas e602 sFLT-1/PlGF ratio = 0.94 [Elecsys 411 sFLT-1/PlGF ratio] +3.5 (r2=0.91, Sy/x=50, n=58). Conclusion sFlt-1 and PlGF measured on Roche Diagnostics Cobas e602 system demonstrated excellent analytical performance and are acceptable for clinical use once approved in the US.

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Applying the concept of uncertainty to the sFlt-1/PlGF cut-offs for diagnosis and prognosis of preeclampsia

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-0477 ◽

2021 ◽

Vol 59 (4) ◽

pp. 681-686

Author(s):

Pacifique Lévy ◽

Safouane Hamdi ◽

Jean Guiboudenche ◽

Marie Clothilde Haguet ◽

Sophie Bailleul ◽

...

Keyword(s):

Quality Control ◽

Growth Factor ◽

Tyrosine Kinase ◽

Error Propagation ◽

Placental Growth Factor ◽

Internal Quality ◽

Diagnosis And Prognosis ◽

Diagnosis By Exclusion ◽

Using Data ◽

Plgf Ratio

Abstract Objectives Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) assays and the corresponding ratios (sFlt-1/PlGF) have been proposed to aid in the diagnosis by exclusion and/or prognosis of preeclampsia (PE). A method for evaluating ratio uncertainties (RUs), based on the theory of error propagation, was applied to the sFlt-1/PlGF ratio. Methods RUs were calculated using data derived from sFlt-1 and PlGF Internal Quality Control (IQC) results collected from four centers using Elecsys (Roche) or Kryptor (Thermo Fisher) sFlt-1 and PlGF assays. The corresponding ratio uncertainties were defined for each ratio value. Results The RUs increased linearly with the sFlt-1/PlGF ratio values. The Elecsys RUs were lower than the Kryptor RUs. Although RUs cannot eliminate differences in ratio values observed among various immunoassays, it can affect interpretation of the sFlt-1/PlGF ratio, especially when results are within the range of predefined PE diagnosis or prognosis cut-offs. Conclusions Since RUs are only a function of PlGF and sFlt-1 precision, they can be calculated for each assay from each laboratory to adjust the interpretation of sFlt-1/PlGF ratio results in the context of PE.

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Inhibin A, activin A, placental growth factor and uterine artery Doppler pulsatility index in the prediction of pre-eclampsia

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.8800 ◽

2011 ◽

Vol 37 (5) ◽

pp. 528-533 ◽

Cited By ~ 45

Author(s):

J. Yu ◽

C. Z. Shixia ◽

Y. Wu ◽

T. Duan

Keyword(s):

Growth Factor ◽

Pulsatility Index ◽

Uterine Artery ◽

Activin A ◽

Placental Growth Factor ◽

Inhibin A ◽

Uterine Artery Doppler

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Identification of patients at risk for early onset and/or severe preeclampsia with the use of uterine artery Doppler velocimetry and placental growth factor

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2006.11.002 ◽

2007 ◽

Vol 196 (4) ◽

pp. 326.e1-326.e13 ◽

Cited By ~ 152

Author(s):

Jimmy Espinoza ◽

Roberto Romero ◽

Jyh Kae Nien ◽

Ricardo Gomez ◽

Juan Pedro Kusanovic ◽

...

Keyword(s):

At Risk ◽

Growth Factor ◽

Early Onset ◽

Uterine Artery ◽

Placental Growth Factor ◽

Severe Preeclampsia ◽

Doppler Velocimetry ◽

Uterine Artery Doppler ◽

Patients At Risk

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Usefulness of the sFlt-1/PlGF (Soluble fms-Like Tyrosine Kinase-1/Placental Growth Factor) Ratio in Diagnosis or Misdiagnosis in Women With Clinical Diagnosis of Preeclampsia

Hypertension ◽

10.1161/hypertensionaha.120.15552 ◽

2020 ◽

Vol 76 (3) ◽

pp. 892-900 ◽

Cited By ~ 1

Author(s):

Alfredo Leaños-Miranda ◽

Ana Graciela Nolasco-Leaños ◽

Reyes Ismael Carrillo-Juárez ◽

Carlos José Molina-Pérez ◽

Liliana Janet Sillas-Pardo ◽

...

Keyword(s):

Growth Factor ◽

Tyrosine Kinase ◽

Clinical Diagnosis ◽

Correct Diagnosis ◽

Kidney Injury ◽

Placental Growth Factor ◽

Adverse Outcomes ◽

Elevated Liver Enzymes ◽

The Relationship ◽

Plgf Ratio

Preeclampsia is characterized by angiogenic imbalance (AI), sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) is useful for its diagnosis and prediction of adverse outcomes, but the relationship among the degrees of AI as assessed by this ratio with the correct diagnosis, clinical characteristics, and outcomes in women with clinical diagnosis of preeclampsia are unclear. We studied 810 women with clinical diagnosis of preeclampsia. Patients were divided into 3 groups based on their degree of AI, evaluated by the sFlt-1/PlGF ratio: no AI (≤38), mild AI (>38–<85), and severe AI (≥85). Patients with no AI were more likely to have comorbidities and false significant proteinuria compared with patients with mild and severe AI ( P <0.001). The rates of preterm delivery, delivery within 14 days, and small-for-gestational-age infant were higher among patients with severe AI than in patients with no and mild AI ( P <0.001) and in patients with mild AI that in those with no AI ( P ≤0.01). The occurrence of any adverse maternal outcome (HELLP syndrome, elevated liver enzymes, thrombocytopenia, placental abruption, acute kidney injury) was only present in patients with severe AI. Interestingly, the frequency of misdiagnosis of preeclampsia was progressively lower as the degrees of AI increased (no AI: 100%, mild AI: 88.2%, and severe AI: 15.6%). We concluded that in women with clinical diagnosis of preeclampsia, severe AI is characterized by high frequency of true preeclampsia and preeclampsia-related adverse outcomes, in contrast, no and mild AI, are characterized by unnecessary early deliveries, often due to misdiagnosis.

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