Suppression of the tissue factor-dependent coagulation cascade: a contributing factor for the development of intratumoral hemorrhage in glioblastoma.

To clarify factors that may contribute to the development of intratumoral hemorrhage, we analyzed the expression of tissue factor (TF), an initiator of the extrinsic coagulation pathway, and of tissue factor pathway inhibitor (TFPI) in glioblastomas with or without massive intratumoral hematoma. Among 196 glioma cases reviewed, there were 13 with macroscopic intratumoral hemorrhage. We focused on the glioblastomas and used immunoblot- and immunohistochemical methods to compare the expression of TF and TFPI in 9 glioblastomas with macroscopic hematoma and 30 glioblastomas without macroscopic hemorrhage. Although TF was expressed in most glioblastomas irrespective of the presence or absence of macroscopic hemorrhage, the staining patterns differed significantly: TF-positive glioma cells were diffusely present in the non-hemorrhage group; in the group with hemorrhage, positive cells, primarily macrophages, were scattered throughout the tissue examined. The expression of TFPI was significantly higher in the group with than in the group without hemorrhage. Our results suggest that local suppression of the TF-dependent coagulation cascade is a contributing factor that permits the occurrence of intratumoral hemorrhage.