Background Fetal growth restriction (FGR) affects 3%–8% of pregnancies and is associated with increased risk of stillbirth and perinatal morbidity, in addition to increased risk of cardiovascular disease later in life. In severe cases of FGR, vascular resistance in the placenta is increased and blood flow reduced, compromising oxygen and nutrient exchange between mother and fetus. Hypoxia and endothelial dysfunction, have both been demonstrated in FGR, and both have the ability to alter thrombosis and haemostasis. The aim of this study was to determine whether there is increased platelet activation and thrombosis in FGR which may contribute to its pathogenesis.
Methods Dual ex-vivo perfusions were performed on placentas from healthy pregnancies (n=10) and those affected by FGR (n=11). Following perfusion (~5 hour), placental cross-sections were processed and stained with H and E and Martius Scarlet Blue for blind-randomised histological analysis or immunofluorescence to analyse levels of fibrin and tissue factor. Fetal blood samples were collected from the umbilical vein immediately following delivery (n=10 healthy; n=8 FGR) and platelet function analysed using the PFA200
Results Placental sections from pregnancies affected by FGR exhibited significantly more thrombi (p<0.01) within the fetal vasculature than healthy placental sections. Thrombi could be observed in both large conduit and small resistance vessels, with many small vessels completely occluded. In FGR, total fibrin deposition in placental tissue was significantly increased (p<0.001), as was fibrin expression specifically located within fetal vessels (p<0.05). In contrast, tissue factor levels remained unaltered. Blood samples from fetal growth restricted babies demonstrated increased closure time in platelet function assays (122±12.6 s) compared to healthy controls (90.10±5.46 s), and platelet counts were significantly reduced (p<0.05). The red blood cell count, white blood cell count and mean platelet volume were not significantly different.
Conclusions These data indicate that in FGR there is increased platelet activation and thrombosis in fetoplacental vessels, which may contribute to increased vascular resistance through the occlusion of small resistance arteries. Anti-thrombotic therapies, which cross the placenta may therefore be beneficial in FGR to prevent placental thrombosis and improve pregnancy outcome.
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