The Factor VIII Bypassing Activity of Prothrombin Complex Concentrates: The Roles of Factor VIla and of Endothelial Cell Tissue Factor

1991 ◽  
Vol 66 (05) ◽  
pp. 559-564 ◽  
Author(s):  
Jerome M Teitel
Keyword(s):  
Factor Viii ◽  
Tissue Factor ◽  
Factor Viia ◽  
Factor Xa ◽  
Procoagulant Activity ◽  
Tissue Factor Expression ◽  
Prothrombin Complex Concentrates ◽  
Cell Tissue ◽  
Factor Expression ◽  
Necrosis Factor

SummaryAn experimental model incorporating cultured endothelial cells (EC) was used to study the "factor VIII bypassing" activity of prothrombin complex concentrates (PCC), a property exploited in the treatment of hemophiliacs with alloantibodies to factor VIII. Two PCC preparations were ineffective as stimuli of tissue factor expression by EC. However, incubation with a combination of PCC plus endotoxin (lipopolysaccharide, LPS) or tumor necrosis factor (TNF) induced much greater tissue factor expression than was seen in response to either substance alone. PCC expressed an additional direct procoagulant activity at the EC surface, which could not be attributed to either thrombin or factor Xa, and which was diminished by an anti-tissue factor antibody. Therefore factor VIIa, which was detectable in both PCC preparations, likely provided this additional direct procoagulant activity at the EC surface. We also excluded the possibility that coagulation proteases contained in or generated in the presence of PCC are protected from inactivation by AT III. Therefore, PCC can indirectly bypass factor VIII by enhancing induced endothelial tissue factor expression, and also possess direct procoagulant activity, probably mediated by factor VIIa.

Inhibition of thrombin generation by the zymogen factor VII: implications for the treatment of hemophilia A by factor VIIa

Blood ◽  
2000 ◽  
Vol 95 (4) ◽  
pp. 1330-1335 ◽  
Author(s):  
Cornelis van 't Veer ◽  
Neal J. Golden ◽  
Kenneth G. Mann
Keyword(s):  
Factor Viii ◽  
Tissue Factor ◽  
Thrombin Generation ◽  
Hemophilia A ◽  
Factor Viia ◽  
Plasma Concentrations ◽  
Factor Xa ◽  
Factor Vii ◽  
Lag Phase ◽  
Single Chain

Factor VII circulates as a single chain inactive zymogen (10 nmol/L) and a trace (∼10-100 pmol/L) circulates as the 2-chain form, factor VIIa. Factor VII and factor VIIa were studied in a coagulation model using plasma concentrations of purified coagulation factors with reactions initiated with relipidated tissue factor (TF). Factor VII (10 nmol/L) extended the lag phase of thrombin generation initiated by 100 pmol/L factor VIIa and low TF. With the coagulation inhibitors TFPI and AT-III present, factor VII both extended the lag phase of the reaction and depressed the rate of thrombin generation. The inhibition of factor Xa generation by factor VII is consistent with its competition with factor VIIa for TF. Thrombin generation with TF concentrations >100 pmol/L was not inhibited by factor VII. At low tissue factor concentrations (<25 pmol/L) thrombin generation becomes sensitive to the absence of factor VIII. In the absence of factor VIII, factor VII significantly inhibits TF-initiated thrombin generation by 100 pmol/L factor VIIa. In this hemophilia A model, approximately 2 nmol/L factor VIIa is needed to overcome the inhibition of physiologic (10 nmol/L) factor VII. At 10 nmol/L, factor VIIa provided a thrombin generation response in the hemophilia model (0% factor VIII, 10 nmol/L factor VII) equivalent to that observed with normal plasma, (100% factor VIII, 10 nmol/L factor VII, 100 pmol/L factor VIIa). These results suggest that the therapeutic efficacy of factor VIIa in the medical treatment of hemophiliacs with inhibitors is, in part, based on overcoming the factor VII inhibitory effect.

scholarly journals CD8+ T-Cell–Derived Tumor Necrosis Factor Can Induce Tissue Factor Expression on Monocytes

2019 ◽  
Vol 220 (1) ◽  
pp. 73-77 ◽  
Author(s):  
Michael L Freeman ◽  
Soumya Panigrahi ◽  
Bonnie Chen ◽  
Steven Juchnowski ◽  
Scott F Sieg ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Necrosis Factor ◽  
Tissue Factor ◽  
Tumor Necrosis ◽  
Cd8 T Cell ◽  
Tissue Factor Expression ◽  
Factor Expression ◽  
Necrosis Factor

scholarly journals Kinetics of lung tissue factor expression and procoagulant activity in bleomycin induced acute lung injury

2015 ◽  
Vol 4 (1) ◽  
Author(s):  
Li Ma ◽  
Ciara M. Shaver ◽  
Brandon S. Grove ◽  
Daphne B. Mitchell ◽  
Nancy E. Wickersham ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Tissue Factor ◽  
Lung Tissue ◽  
Procoagulant Activity ◽  
Tissue Factor Expression ◽  
Factor Expression ◽  
Kinetics Of

Induction of Tissue Factor Expression in Whole Blood: Lack of Evidence for the Presence of Tissue Factor Expression in Granulocytes

2000 ◽  
Vol 83 (06) ◽  
pp. 861-867 ◽  
Author(s):  
Bjarne Østerud ◽  
Jan Olsen ◽  
L. Vijaya Rao
Keyword(s):  
Tumor Necrosis Factor ◽  
Tissue Factor ◽  
Whole Blood ◽  
Blood Cells ◽  
Tumor Necrosis ◽  
Platelet Rich Plasma ◽  
Tissue Factor Expression ◽  
Factor Expression ◽  
Activated Monocytes ◽  
Necrosis Factor

SummaryThe present investigation was undertaken to explore the effect of platelets, tumor necrosis factor (TNF) and phorbel ester [phorbol 12-myristate 13-acetate (PMA)] on lipopolysaccharide (LPS)-induced tissue factor (TF) activity and TF antigen by using Western blot and ELISA-techniques. LPS was found to induce correlating levels of TF antigen and the activity in monocytes. TNF and PMA, when used alone, failed to induce TF activity and the antigen in monocytes, but enhanced the LPS-induced TF activity and the antigen by 2 to 3-fold. Addition of platelet rich plasma to isolated blood cells enhanced the LPS-induced TF activity but not the antigen levels in monocytes. In contrast to whole platelets, platelet lysates enhanced both LPS-induced TF activity and the antigen. Granulocytes isolated from heparinized plasma incubated for 2 or 24 h with LPS alone or together with PMA, failed to generate TF antigen or the activity. Although granulocyte preparations isolated from whole blood that was incubated for 24 h with LPS and PMA apparently possessed a significant amount of TF activity and the antigen, this could be accounted for by trace levels of contaminating monocytes. Upregulation of LPS-induced TF activity but not the antigen by platelets in the presence of granulocytes suggests that the increased TF activity could be the result of PS enrichment of monocytes by fusion or platelets with activated monocytes.

scholarly journals Selective factor VIII activation by the tissue factor–factor VIIa–factor Xa complex

Blood ◽  
2017 ◽  
Vol 130 (14) ◽  
pp. 1661-1670 ◽  
Author(s):  
Yuichi Kamikubo ◽  
G. Loredana Mendolicchio ◽  
Antonella Zampolli ◽  
Patrizia Marchese ◽  
Andrea S. Rothmeier ◽  
...  
Keyword(s):  
Factor Viii ◽  
Tissue Factor ◽  
Factor Viia ◽  
Factor Xa

Publisher's Note: There is an Inside Blood Commentary on this article in this issue.

scholarly journals Factor Xa Induces Tissue Factor Expression in Endothelial Cells by P44/42 MAPK and NF-κB-Dependent Pathways

2011 ◽  
Vol 169 (2) ◽  
pp. 319-327 ◽  
Author(s):  
Rong Jiang ◽  
Ning-Ping Wang ◽  
Kenichi A. Tanaka ◽  
Jerrold H. Levy ◽  
Robert A. Guyton ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tissue Factor ◽  
Factor Xa ◽  
Tissue Factor Expression ◽  
Factor Expression
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