A new observational study suggests that routine platelet measurements during pregnancy may help identify women who do not respond to low-dose aspirin and subsequently develop preeclampsia. The findings indicate that these common and inexpensive tests could support early identification of high-risk pregnancies for tailored intervention.
Researchers analyzed data from 993 women enrolled in an ancillary study of the FORECAST trial, which evaluated first-trimester preeclampsia screening and prevention. Participants were categorized into three groups: those who developed preeclampsia despite taking aspirin (clinically defined as aspirin nonresponsiveness), those who took aspirin and did not develop preeclampsia, and those at low risk who were not prescribed aspirin.
Platelet count (PC), mean platelet volume (MPV), and the PC/MPV ratio were measured at three gestational stages: 9–13 weeks (prior to aspirin administration), 20–24 weeks, and 30–34 weeks. In women who developed preeclampsia despite aspirin treatment, PC declined significantly in the second trimester. By the third trimester, these women also had significantly higher MPV and a lower PC/MPV ratio compared with those who remained preeclampsia-free.
Multivariable logistic regression models showed that PC at 20–24 weeks and PC, MPV, and PC/MPV ratio at 30–34 weeks were significantly associated with aspirin nonresponsiveness. The predictive value of these indices improved when combined with maternal factors such as body mass index, parity, and chronic hypertension. For example, the adjusted odds ratio (AOR) for a low PC/MPV ratio at 30–34 weeks was 0.670 (95% CI, 0.539–0.834; P < .001), and the area under the curve (AUC) reached 0.762 when combined with maternal characteristics.
To evaluate platelet activation at the maternal–fetal interface, the investigators performed Opal immunofluorescence staining on placental villous and decidual tissues. CD42b (a platelet-specific marker) and CD62P (an activation marker) were elevated in the preeclamptic group compared with controls. Manders’ coefficient revealed increased colocalization of these markers in both tissue types among women with preeclampsia, indicating enhanced platelet activation.
To explore the molecular mechanisms involved, the team performed RNA sequencing on platelets isolated from peripheral blood, placental villous tissue, and decidua. Differential expression analysis revealed 20, 618, and 1,819 genes altered in blood, placenta, and decidua, respectively, between preeclamptic and nonpreeclamptic women. Functional enrichment analysis showed significant upregulation of the PI3K-Akt signaling pathway in the placenta and the Wnt signaling pathway in the decidua—both pathways known to regulate platelet activity and vascular remodeling.
Quantitative real-time polymerase chain reaction (RT-qPCR) confirmed increased expression of FKBP5, LAMA5, FGG, and FZD5 in the preeclamptic group. Notably, FKBP5, a gene linked to platelet procoagulant activity, was elevated in peripheral blood samples from women with preeclampsia.
According to the authors, these findings underscore that monitoring platelet indices may assist in identifying women unlikely to benefit from aspirin therapy. The investigators recommend further research to clarify the mechanisms of aspirin nonresponsiveness and determine whether these indices can be integrated into routine clinical risk stratification.
No competing interests were declared.
Source: BMC Medicine