DIAGNOS TICS
this incurring tragic human cost, it is also a matter of huge concern for hospital Trusts intent on avoiding litigation as a result of pre-eclampsia not being recognised and managed in a timely manner. Until recently, the diagnosis of pre- eclampsia has been based on a combination of general clinical features and laboratory- based tests, followed by a ‘watch and wait’ policy. A clear and timely method that accurately flags pre-eclampsia has unsurprisingly been the holy grail for antenatal care for many years and, recently, attention has turned to the measurement of placenta-derived growth factors to fill this void.
The emergence of biomarkers Angiogenic biomarkers, including placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1), are increasingly being implemented as useful tools in the pre-eclampsia diagnostic pathway, answering key questions that help clinicians to know exactly what they’re dealing with. In particular, PlGF-based testing has a high negative predictive value and has already been adopted to rule-out pre-eclampsia in several different countries in Europe, including the UK, as well as currently being rolled out in the Middle East. PlGF is a protein involved in the development of spiral arteries within the placenta. In normal pregnancies, the concentration of PlGF rises as gestation progresses, reaching a peak at 26-30 weeks before decreasing towards term. But in pre-eclampsia, PlGF levels do not rise and fall to the same degree, signalling placental dysfunction caused by the arteries straightening and the lumen narrowing, which causes a reduction in the nutrients reaching the fetus. Crucially, it appears that abnormally low concentrations of PlGF seem to precede the clinical onset of pre-eclampsia and may even pre-date symptoms by up to 10 weeks. Conversely, sFlt-1 concentrations increase towards term in healthy pregnancies and are prematurely elevated in women with pre-eclampsia.
The PARROT trial – validating PIGF for clinical practice Evidence supporting the implementation of these newly recognised biomarkers mounted in 2019, with the publication of the PARROT study in the Lancet.10
The
multicentre trial looked at the value of PlGF measurement in 1,035 women with suspected pre-eclampsia from 11 large maternity units in the UK over a period of 16 months, reporting on its effectiveness in reducing maternal and perinatal adverse effects, as well as its economic impact on healthcare resources. Results showed that PlGF testing significantly helped decision-
JANUARY 2023
The power of POC testing – when fast results count
The choice of location for testing PlGF is dictated by the individual preference of each NHS Trust. However, for conditions like pre- eclampsia, a quick turnaround is immensely valuable, giving actionable results in a matter of minutes so that clinicians can start to plan the appropriate patient care.
making for suspected pre-eclampsia patients and that this, in turn, substantially reduced poor patient outcomes while also keeping costs down for the NHS. In the same year, NHS England’s Innovation and Technology Payment (ITP) programme also focused its attention on evaluating two commercially available, NICE-approved assay options for PlGF, with the aim of removing financial and procurement barriers to rapidly introduce the new test within England. The first test, Quidel Triage PLGF Test, measures PlGF alone, both at the point of patient care and in a clinical lab, whereas the second, Elecsys sFlt-1/PlGF (Roche Diagnostics) quantifies the ratio of sFlt-1 and PlGF and is available as a lab-based service. To date, the CE-marked Quidel Triage PLGF test evaluated by the ITP programme has been implemented in more than 60 Trusts in England, both as a point-of-care (POC) assay and a laboratory-based test. This single-use, fluorescence immunoassay takes minutes to perform on a well- known, compact and reliable instrument, Quidel Triage MeterPro, therefore allowing hospitals to place it in a POC setting or within a laboratory depending on individual preference.
It quantifies PlGF concentration in the range of 12-3,000 pg/ml and gives a result in approximately 15 minutes. Sites already using the system are currently split 50/50 between POC or lab use. Its small footprint means that it can be easily moved between locations so users are finding that they can place it according to what works best for that particular Trust, changing that approach at a later date if necessary.
POC PlGF testing also gives maternity services a higher degree of flexibility, so that access can be given anywhere along the antenatal pathway around the clock – from maternity day assessment units to antenatal clinics. It is perhaps especially important for those living in rural areas, where women, dependant on the test result, could potentially be monitored closer to home rather than being admitted to a remote secondary care hospital as a precaution. Midwives in several Trusts are conducting the test in antenatal clinics or day assessment units with great success; it is a very simple method and they can see the clinical benefit, as well as the emotional reassurance it gives to expectant mothers, so they have been very keen to learn how to perform it to the benefit of all. Alternatively, other locations have chosen for the lab teams to run the test, a decision that seems to be partly shaped by the current shortage of midwives.
Benefits
NICE recommends PlGF-based testing to help rule-out pre-eclampsia11
and the
feedback from clinicians, so far, has been overwhelmingly positive. Access to PlGF results is supporting them in quick and effective diagnosis and management and is making a real difference to patient care. Women most commonly present with signs and symptoms of pre-eclampsia after 20 weeks gestation, and PlGF testing is suitable for between 20 weeks, and 34 weeks and six days of a pregnancy. Receiving this key information within a
very short space of time – a maximum of 30 minutes for a POC test, longer for lab-based tests that are subject to sample transfer times – is allowing them to make far quicker clinical judgments and decisions. Only women who clearly need secondary care are being admitted, while others identified as not at risk are being managed as outpatients, which is making huge savings, both in terms of cost to the NHS, as well as inpatient, lab and ultrasound time and resources within each individual
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