Antithrombotic Properties of a Truncated Recombinant Tissue Factor Pathway Inhibitor in an Experimental Venous Thrombosis Model

1993 ◽  
Vol 23 (1) ◽  
pp. 112-117 ◽  
Author(s):  
Jan Holst ◽  
Bengt Lindblad ◽  
David Bergqvist ◽  
Ole Nordfang ◽  
Per B. Østergaard ◽  
...  
1999 ◽  
Vol 82 (07) ◽  
pp. 1-5 ◽  
Author(s):  
Michael Schmidt ◽  
Christian Götting ◽  
Britt Schwenz ◽  
Stefan Lange ◽  
Gert Müller-Berghaus ◽  
...  

SummaryTissue factor pathway inhibitor (TFPI) is an important regulator in the extrinsic blood coagulation pathway. Although the regulatory biochemical role of TFPI is evident, the clinical significance of this proteinase inhibitor remains to be elucidated. The definition of a clinical TFPI deficiency seems to be more complex than that of other coagulation inhibitors because the activity and concentration of circulating TFPI can not be considered a true measure of in vivo levels. Its determination in plasma samples by immunological methods or functional assays has been shown to be inadequate in the detection of a clinical deficiency.Therefore, we screened genomic DNA samples of blood donors and thrombotic patients for alterations in the TFPI gene to assess the influence of a modified TFPI in venous thromboembolic diseases. We detected a single nucleotide substitution in exon 7 (536C→T) leading to a proline to leucine exchange at amino acid position 151 of the protein ([P151L]TFPI) and found the prevalence of heterozygous carriers in German unrelated blood donors to be 0.2% (n = 5120).Four unrelated persons out of 14 probands carrying the genetic variation could be linked to venous thrombosis. For calculation of a potential risk for venous thrombosis for carriers of the mutation we investigated healthy blood donors about thrombotic events. 7 out of 308 blood donors were found to have a history of venous thrombosis, one of them carried the TFPI mutation. Statistical calculation showed a significant relative risk for venous thrombosis for individuals with the trait (odds ratio, 9.3; confidence interval, 1.8-48.6; p <0.01).


2001 ◽  
Vol 113 (2) ◽  
pp. 537-543 ◽  
Author(s):  
Ali Amini-Nekoo ◽  
T. Simon Futers ◽  
Marco Moia ◽  
Pier M. Mannucci ◽  
Peter J. Grant ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Xianming Fei ◽  
Huan Wang ◽  
Wufeng Yuan ◽  
Mingyi Wo ◽  
Lei Jiang

Activation of blood coagulation contributes to cancer progression. Tissue factor pathway inhibitor-1 (TFPI-1) is the main inhibitor of extrinsic coagulation pathway. The aim of this study is to assess the predicting significance of TFPI-1 for thrombotic complication and metastasis in lung cancer patients. Total of 188 non-small cell lung cancer (NSCLC) patients were included in this study. Plasma TFPI-1, D-dimer (D-D), antithrombin (AT), Fibrinogen (Fbg), and coagulating factor VIII activity (FVIII:C) were measured. In NSCLC patients, significantly decreased TFPI-1 and AT and increased D-D, Fbg, and FVIII:C levels were observed, and there was a significant correlation between TFPI-1 and other hemostatic parameters (P<0.001, resp.). NSCLC patients with deep venous thrombosis (DVT) or metastasis had significantly lower TFPI-1 levels than those without DVT or metastasis (P<0.01, resp.). Multivariate regression revealed that TFPI-1 acted as a predictor for DVT or tumor metastasis in NSCLC patients [OR: 4.15 or 3.28,P<0.05, resp.]. The area under ROC curve of TFPI-1 was 0.905 (95% CI, 0.842~0.967) or 0.828 (95% CI, 0.742~0.915) for predicting DVT or metastasis (P<0.001, resp.). The optimal point of TFPI-1 was 57.7 or 54.3 ng/mL for predicting DVT or metastasis, respectively. Combination of TFPI-1 and D-D measurements can improve the predicting power for DVT or metastasis in NSCLC patients. Our findings suggested that TFPI-1 was a valuable predictor of DVT and tumor metastasis in NSCLC patients.


2013 ◽  
Vol 132 (5) ◽  
pp. 627-634 ◽  
Author(s):  
Feras Abu Saadeh ◽  
Lucy Norris ◽  
Sharon O’Toole ◽  
Bashir M. Mohamed ◽  
Ream Langhe ◽  
...  

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