9 research outputs found
Factor XI localization in human deep venous thrombus and function of activated factor XI on venous thrombus formation and hemostasis
Background
Novel anticoagulants targeting coagulation factor (F)XI/activated FXI (FXIa) are currently under development. However, whether FXI is present in human deep vein thrombosis (DVT) and whether FXIa and activated FX (FXa) play different roles in venous thrombus formation and hemostasis remain unclear.
Objectives
To determine the presence of FXI in DVT and the effects of direct oral FXIa and FXa inhibitors on venous thrombus formation and hemostasis in rabbits and on in vitro thrombus formation.
Methods
We immunohistochemically assessed FXI localization in human-aspirated DVT (n = 15). Additionally, we compared thrombus formation induced by endothelial denudation and stenosis or stasis in the jugular vein and skin bleeding time and volume between rabbits treated with direct FXIa inhibitors (ONO-1600586) and FXa inhibitors (rivaroxaban). Ex vivo rabbit and human blood were perfused in a flow chamber under low-shear rates (70/s).
Results
FXI was localized in all DVT, predominantly in fibrin-rich areas. The FXI immunopositive area in the nonorganizing area was greater than that in the organizing area. Although FXIa and FXa inhibitors comparably inhibited venous thrombus formation, FXIa inhibitors did not affect bleeding time or volume in rabbits. FXIa or FXa inhibitors mildly or strongly inhibited fibrin formation at low-shear rates, respectively. Furthermore, the FXIa inhibitor suppressed human FXIa activity, thrombin generation, and fibrin formation during perfusion.
Conclusion
The pathologic findings of human DVT suggest FXI’s role in human DVT. FXIa inhibitors may inhibit less fibrin formation than FXa inhibitors and may explain the minor role of FXIa in hemostasis.Citation: Nobuyuki Oguri, Toshihiro Gi, Eriko Nakamura, Kazunari Maekawa, Eiji Furukoji, Hoshimi Okawa, Sho Kouyama, Saki Horiuchi, Akira Sawaguchi, Tatefumi Sakae, Minako Azuma, Yujiro Asada, Atsushi Yamashita, Factor XI localization in human deep venous thrombus and function of activated factor XI on venous thrombus formation and hemostasis, Research and Practice in Thrombosis and Haemostasis, 9(2), 102720-102720, 2025-02, https://doi.org/10.1016/j.rpth.2025.10272
The early movement for normalizing biology education in Russia after lysenko's downfall in 1965
journal articl
Le miroir du monde, ou, epitome du Theatre d'Abraham Ortelius. Auquel se represente, tant par figures que par les characteres, la vraye situation, nature & propriete ?de la terre vniuerselle. Aggrandi & enrichi, entre autres, de plusieurs belles cartes du Pais?-bas.
Mode of access: Internet.Ochenta mapas xil. en el recto de las p. 18 a 97.Sign.: [A&E]4, F-Bb4
A case of multifocal sclerosis angiomatoid nodular transformations of the spleen occurring after partial splenic infarction with transcatheter arterial embolization for splenic artery aneurysm
Citation:
Kai, K., Hamada, T., Sakae, T. et al. A case of multifocal sclerosis angiomatoid nodular transformations of the spleen occurring after partial splenic infarction with transcatheter arterial embolization for splenic artery aneurysm. Clin J Gastroenterol 17, 198–203 (2024). https://doi.org/10.1007/s12328-023-01869-
Expression of fibroblast activation protein-α in human deep vein thrombosis
Background
Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is associated with wound healing, cancer-associated fibroblasts, and chronic fibrosing diseases. However, its expression in deep vein thrombosis (DVT) remains unclear. Therefore, this study investigated FAP expression and localization in DVT.
Methods
We performed pathological analyses of the aspirated thrombi of patients with DVT (n = 14), classifying thrombotic areas in terms of fresh, cellular lysis, and organizing reaction components. The organizing reaction included endothelialization and fibroblastic reaction. We immunohistochemically examined FAP-expressed areas and cells, and finally analyzed FAP expression in cultured dermal fibroblasts.
Results
All the aspirated thrombi showed a heterogeneous mixture of at least two of the three thrombotic areas. Specifically, 83 % of aspirated thrombi showed fresh and organizing reaction components. Immunohistochemical expression of FAP was restricted to the organizing area. Double immunofluorescence staining showed that FAP in the thrombi was mainly expressed in vimentin-positive or α-smooth muscle actin-positive fibroblasts. Some CD163-positive macrophages expressed FAP. FAP mRNA and protein levels were higher in fibroblasts with low-proliferative activity cultured under 0.1 % fetal bovine serum (FBS) than that under 10 % FBS. Fibroblasts cultured in 10 % FBS showed a significant decrease in FAP mRNA levels following supplementation with hemin, but not with thrombin.
Conclusions
The heterogeneous composition of venous thrombi suggests a multistep thrombus formation process in human DVT. Further, fibroblasts or myofibroblasts may express FAP during the organizing process. FAP expression may be higher in fibroblasts with low proliferative activity
