scholarly journals A first-in-human study of the safety, tolerability, pharmacokinetics and pharmacodynamics of PF-06741086, an anti-tissue factor pathway inhibitor mAb, in healthy volunteers

2018 ◽  
Vol 16 (9) ◽  
pp. 1722-1731 ◽  
Author(s):  
M. Cardinal ◽  
C. Kantaridis ◽  
T. Zhu ◽  
P. Sun ◽  
D. D. Pittman ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Human Study ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Tissue Factor Pathway

Decreased Plasma Tissue Factor Pathway Inhibitor Levels in Patients with Thrombotic Thrombocytopenic Purpura

1995 ◽  
Vol 73 (01) ◽  
pp. 010-014 ◽  
Author(s):  
Hideo Wada ◽  
Masayuki Kobayashi ◽  
Yoshihiro Wakita ◽  
Minori Shimura ◽  
Tutomu Nakase ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Healthy Volunteers ◽  
Tissue Factor ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Plasma Levels ◽  
Tissue Factor Pathway Inhibitor ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Thrombocytopenic Purpura ◽  
Tissue Factor Pathway

SummaryWe measured plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC) to examine the relationship between TFPI and vascular endothelial cell injury. TF antigen was detected in the plasma of healthy volunteers, and the levels were significantly increased in the patients with DIC, but decreased slightly in those with TTP. Plasma TFPI levels were significantly decreased in patients with TTP compared with those in healthy volunteers. The concentration of plasma thrombomodulin (TM) antigen was significantly higher in those with TTP than in normal volunteers. One month after treatment, TTP patients showed a significant decrease in plasma TM levels, and a significant increase, in plasma TFPI levels, but plasma levels of TF antigen were not significantly increased. As plasma TFPI/TF ratio was significantly increased after treatment, the hypercoagulable state was therefore improved after treatment. There was no significant difference in plasma TF and TFPI levels between those who achieved complete remission (CR) and those who died. However, plasma TM levels were significantly higher in those who died than in those who achieved CR. Plasma TFPI levels might reflect injury of vascular endothelial cells as do plasma TM levels, and decreased plasma TFPI/TF ratio and vascular endothelial cell injuries might play causative roles in TTP.

Effects of low-molecular-weight dermatan sulfate on coagulation, fibrinolysis and tissue factor pathway inhibitor in healthy volunteers

1996 ◽  
Vol 7 (1) ◽  
pp. 49-56 ◽  
Author(s):  
J. Harenberg ◽  
M. Jeschek ◽  
M. Acker ◽  
R. Malsch ◽  
G. Huhle ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Healthy Volunteers ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Dermatan Sulfate ◽  
Low Molecular Weight ◽  
Tissue Factor Pathway

Elevated Tissue Factor and Tissue Factor Pathway Inhibitor Circulating Levels in Ischaemic Heart Disease Patients

1998 ◽  
Vol 79 (03) ◽  
pp. 495-499 ◽  
Author(s):  
Anna Maria Gori ◽  
Sandra Fedi ◽  
Ludia Chiarugi ◽  
Ignazio Simonetti ◽  
Roberto Piero Dabizzi ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischaemic Heart Disease ◽  
Tissue Factor ◽  
Plasma Levels ◽  
Tissue Factor Pathway Inhibitor ◽  
Common Source ◽  
Previous Myocardial Infarction ◽  
Control Subjects ◽  
Tissue Factor Pathway ◽  
Circulating Levels

SummarySeveral studies have shown that thrombosis and inflammation play an important role in the pathogenesis of Ischaemic Heart Disease (IHD). In particular, Tissue Factor (TF) is responsible for the thrombogenicity of the atherosclerotic plaque and plays a key role in triggering thrombin generation. The aim of this study was to evaluate the TF/Tissue Factor Pathway Inhibitor (TFPI) system in patients with IHD.We have studied 55 patients with IHD and not on heparin [18 with unstable angina (UA), 24 with effort angina (EA) and 13 with previous myocardial infarction (MI)] and 48 sex- and age-matched healthy volunteers, by measuring plasma levels of TF, TFPI, Prothrombin Fragment 1-2 (F1+2), and Thrombin Antithrombin Complexes (TAT).TF plasma levels in IHD patients (median 215.4 pg/ml; range 72.6 to 834.3 pg/ml) were significantly (p<0.001) higher than those found in control subjects (median 142.5 pg/ml; range 28.0-255.3 pg/ml).Similarly, TFPI plasma levels in IHD patients were significantly higher (median 129.0 ng/ml; range 30.3-316.8 ng/ml; p <0.001) than those found in control subjects (median 60.4 ng/ml; range 20.8-151.3 ng/ml). UA patients showed higher amounts of TF and TFPI plasma levels (TF median 255.6 pg/ml; range 148.8-834.3 pg/ml; TFPI median 137.7 ng/ml; range 38.3-316.8 ng/ml) than patients with EA (TF median 182.0 pg/ml; range 72.6-380.0 pg/ml; TFPI median 115.2 ng/ml; range 47.0-196.8 ng/ml) and MI (TF median 213.9 pg/ml; range 125.0 to 341.9 pg/ml; TFPI median 130.5 ng/ml; range 94.0-207.8 ng/ml). Similar levels of TF and TFPI were found in patients with mono- or bivasal coronary lesions. A positive correlation was observed between TF and TFPI plasma levels (r = 0.57, p <0.001). Excess thrombin formation in patients with IHD was documented by TAT (median 5.2 μg/l; range 1.7-21.0 μg/l) and F1+2 levels (median 1.4 nmol/l; range 0.6 to 6.2 nmol/l) both significantly higher (p <0.001) than those found in control subjects (TAT median 2.3 μg/l; range 1.4-4.2 μg/l; F1+2 median 0.7 nmol/l; range 0.3-1.3 nmol/l).As in other conditions associated with cell-mediated clotting activation (cancer and DIC), also in IHD high levels of circulating TF are present. Endothelial cells and monocytes are the possible common source of TF and TFPI. The blood clotting activation observed in these patients may be related to elevated TF circulating levels not sufficiently inhibited by the elevated TFPI plasma levels present.

Behandlung der tiefen Venenthrombose

2000 ◽  
Vol 20 (01) ◽  
pp. 65-69 ◽  
Author(s):  
A. Loew ◽  
H. Riess
Keyword(s):  
Tissue Factor ◽  
Medikamentöse Therapie ◽  
Tissue Factor Pathway Inhibitor ◽  
Tissue Factor Pathway ◽  
Faktor Xa

ZusammenfassungVon den verschiedenen, zur Behandlung der tiefen Venenthrombose zur Verfügung stehenden Optionen, stellt die akute Antikoagulanzientherapie mit Heparinen, insbesondere niedermolekularen Heparinen, gefolgt von der frühzeitig überlappend eingeleiteten oralen Antikoagulation, das Standardvorgehen dar. Thrombolyse, Thrombektomie und Implantation von Kavaschirmfiltern kommen nur bei wenigen Patienten sinnvoll in Betracht. Während somit die medikamentöse Therapie mit Heparinen und Cumarinen die medikamentöse Standardbehandlung darstellt, sind begleitende Therapiemaßnahmen, wie die Notwendigkeit zur initialen Immobilisation der Patienten sowie zur Kompressionsbehandlung bei tiefen Venenthrombosen in ihrer Wertigkeit ungesichert und Gegenstand kontroverser Diskussionen. Darüber hinaus werden die optimale Dauer der oralen Antikoagulation, der Stellenwert einer prolongierten Therapie mit niedermolekularen Heparinen sowie der Stellenwert neuerer Antithrombotika wie Antithrombine, Faktor-Xa-Hemmstoffe und »Tissue factor pathway inhibitor« diskutiert.

Sign in / Sign up

Export Citation Format

Share Document