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71: Significant differences in dynamic platelet behavior in gestational hypertension and preeclampsia compared with intrauterine growth restriction suggesting alternate pathways in utero-placental disease
Platelet mediated thrombosis occurs when platelets tether adhere and roll on Von Willebrand factor (vWF). We developed a novel microfluidic assay that measures these parameters thus replicating the behavior of platelets in vasculature. Using this dynamic assay of platelet function we investigated patients with preeclampsia (PET), gestational hypertension (GH) & intrauterine growth restriction (IUGR) which has never been shown to date.
Patients were recruited from 24wks gestation. 100ul of blood from each donor was fluorescently-labeled and perfused over a vWF coated polymer chip at arterial shear conditions. Images of platelet interactions at the surface were captured using a vacuum-cooled Andor camera. Multiple parameters of platelet behavior were assessed in each condition and all samples had a triplicate run performed.
28 samples comprising of GH (n=10), PET (n=12) and IUGR (n=6) were obtained and were compared to 13 normal pregnant controls. In GH platelets demonstrated less stasis, less translocation, and less end-surface coverage compared with healthy controls (p<0.0001) with similar findings in PET. However, in IUGR platelets demonstrated more stasis, equal translocation and less surface coverage (p= 0.0001), see table.
Our novel findings show significant differences of in vivo platelet behavior in pregnancies with GH and PET in contrast to IUGR, when compared to healthy pregnant controls. In GH and PET platelets appear less reactive to the vWF surface demonstrating global hypo-reactivity. In IUGR platelets are more static suggesting a tendency to micro-thrombus formation. For the first time we have demonstrated real-time platelet activity in common pregnancy disorders. These results may challenge the theory of a homogenous pathological pathway in utero-placental disease leading to more advanced targeted platelet therapies for these conditions in the future.
1Multiple parameters of platelet function for controls, GH, PET and IUGR
Nstatic, platelets that have not traveled more than 1.5 times their radius from the start to end of the flow run; Ntrans, are platelets that have traveled more than 1.5 times their radius from the start to end of the flow run; %Motion, the percentage of time that a platelet spends moving before stably adhering to the vWF surface; %Surface coverage end, the percentage of platelets (Nstatic and Ntrans) captured in the final image in comparison to the background.