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AIM To analyze the differential genetic expression and protein localization of thrombomodulin (THBD) and tissue factor (F3) in the placentas of pregnancies affected by preeclampsia. METHODS We assessed the expression of THBD and F3 by immunohistochemistry and real-time polymerase chain reaction (PCR) in placentas from 20 PE cases: 10 early-onset PE placentas, 10 late-onset PE placentas, and 10 control cases (normal pregnancies). RESULTS In cases, we found higher THBD and F3 RNA levels in placental tissue. Protein expression in controls differed from that in late-onset PE placentas, which had lower THBD levels in syncytiotrophoblasts and amniotic cells. Likewise, late-onset PE placentas exhibited comparatively lower F3 expression in the perivillous fibrin. In contrast, early-onset PE had high F3 expression in the subdecidual fibrin. We found no significant differences in the F3/THBD ratio between the groups. CONCLUSION Our study supports evidence that shows the involvement of F3 and THBD in placental disorders. Furthermore, this finding contributes to a better understanding of the physio-pathological role that these molecules may play in the development of this heterogeneous disease.