Search

Background: Puumala orthohantavirus (PUUV) causes hemorrhagic fever with renal syndrome (HFRS). Patients with HFRS have an activated coagulation system with increased risk of disseminated intravascular coagulation (DIC) and venous thromboembolism (VTE). The aim of the study was to determine whether circulating extracellular vesicle tissue factor (EVTF) activity levels associates with DIC and VTE (grouped as intravascular coagulation) in HFRS patients., Methods: Longitudinal samples were collected from 88 HFRS patients. Patients were stratified into groups of those with intravascular coagulation (n = 27) and those who did not (n = 61). We measured levels of circulating EVTF activity, fibrinogen, activated partial prothrombin time, D-dimer, tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), and platelets., Results: Plasma EVTF activity was transiently increased during HFRS. Levels of EVTF activity were significantly associated with plasma tPA and PAI-1, suggesting that endothelial cells could be a potential source. Patients with intravascular coagulation had significantly higher peak EVTF activity levels compared with those who did not, even after adjustment for sex and age. The peak EVTF activity value predicting intravascular coagulation was 0.51 ng/L with 63% sensitivity and 61% specificity with area under the curve = 0.63 (95% confidence interval, 0.51-0.76) and P = .046., Conclusions: Plasma EVTF activity during HFRS is associated with intravascular coagulation., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

The intrinsic tenase complex (FIXa-FVIIIa) of the intrinsic coagulation pathway and, to a lesser extent, thrombin-mediated activation of FXI, are necessary to amplify tissue factor (TF)-FVIIa-initiated thrombin generation. In this study, we determined the contribution of murine FIX and FXI to TF-dependent thrombin generation in vitro. We further investigated TF-dependent FIX activation in mice and the contribution of this pathway to hemostasis. Thrombin generation was decreased in FIX- but not in FXI-deficient mouse plasma. Furthermore, injection of TF increased levels of FIXa-antithrombin complexes in both wild-type and FXI-/- mice. Genetic studies were used to determine the effect of complete deficiencies of either FIX or FXI on the survival of mice expressing low levels of TF. Low-TF;FIX-/y male mice were born at the expected frequency, but none survived to wean. In contrast, low-TF;FXI-/- mice were generated at the expected frequency at wean and had a 6-month survival equivalent to that of low-TF mice. Surprisingly, a deficiency of FXI, but not FIX, exacerbated the size of blood pools in low-TF placentas and led to acute hemorrhage and death of some pregnant dams. Our data indicate that FIX, but not FXI, is essential for survival of low-TF mice after birth. This finding suggests that TF-FVIIa-mediated activation of FIX plays a critical role in murine hemostasis. In contrast, FXI deficiency, but not FIX deficiency, exacerbated blood pooling in low-TF placentas, indicating a tissue-specific requirement for FXI in the murine placenta under conditions of low TF., (© 2020 by The American Society of Hematology.)

Tissue factor (TF) is the high-affinity receptor and cofactor for factor (F)VII/VIIa. The TF-FVIIa complex is the primary initiator of blood coagulation and plays an essential role in hemostasis. TF is expressed on perivascular cells and epithelial cells at organ and body surfaces where it forms a hemostatic barrier. TF also provides additional hemostatic protection to vital organs, such as the brain, lung, and heart. Under pathological conditions, TF can trigger both arterial and venous thrombosis. For instance, atherosclerotic plaques contain high levels of TF on macrophage foam cells and microvesicles that drives thrombus formation after plaque rupture. In sepsis, inducible TF expression on monocytes leads to disseminated intravascular coagulation. In cancer patients, tumors release TF-positive microvesicles into the circulation that may contribute to venous thrombosis. TF also has nonhemostatic roles. For instance, TF-dependent activation of the coagulation cascade generates coagulation proteases, such as FVIIa, FXa, and thrombin, which induce signaling in a variety of cells by cleavage of protease-activated receptors. This review will focus on the roles of TF in protective hemostasis and pathological thrombosis., (© 2018 American Heart Association, Inc.)