Journal ArticleDOI
Activation of coagulation after administration of tumor necrosis factor to normal subjects.
T. van der Poll,H. R. Büller,H. ten Cate,C. H. Wortel,Kenneth A. Bauer,S. J. H. Van Deventer,C. E. Hack,H. P. Sauerwein,Robert D. Rosenberg,J W ten Cate +9 more
Reads0
Chats0
TLDR
It is concluded that a single injection of tumor necrosis factor elicits a rapid and sustained activation of the common pathway of coagulation, probably induced through the extrinsic route and could play an important part in the earlyactivation of the hemostatic mechanism in septicemia.Abstract:
Tumor necrosis factor has been implicated in the activation of blood coagulation in septicemia, a condition commonly associated with intravascular coagulation and disturbances of hemostasis. To evaluate the early dynamics and the route of the in vivo coagulative response to tumor necrosis factor, we performed a controlled study in six healthy men, monitoring the activation of the common and intrinsic pathways of coagulation with highly sensitive and specific radioimmunoassays. Recombinant human tumor necrosis factor, administered as an intravenous bolus injection (50 micrograms per square meter of body-surface area), induced an early and short-lived rise in circulating levels of the activation peptide of factor X, reaching maximal values after 30 to 45 minutes (mean +/- SEM increase after 45 minutes, 34.2 +/- 18.2 percent; tumor necrosis factor vs. saline, P = 0.015). This was followed by a gradual and prolonged increase in the plasma concentration of the prothrombin fragment F1+2, peaking after four to five hours (mean increase after five hours, 348.0 +/- 144.8 percent; tumor necrosis factor vs. saline, P less than 0.0001). These findings signify the formation of factor Xa (activated factor X) and the activation of prothrombin. Activation of the intrinsic pathway could not be detected by a series of measurements of the plasma levels of factor XII, prekallikrein, factor XIIa-C1 inhibitor complexes, kallikrein-C1 inhibitor complexes, and the activation peptide of factor IX. The delay between the maximal activation of factor X and that of prothrombin amounted to several hours, indicating that neutralization of factor Xa activity was slow. We conclude that a single injection of tumor necrosis factor elicits a rapid and sustained activation of the common pathway of coagulation, probably induced through the extrinsic route. Our results suggest that tumor necrosis factor could play an important part in the early activation of the hemostatic mechanism in septicemia.read more
Citations
More filters
Journal ArticleDOI
Disseminated Intravascular Coagulation
Marcel Levi,Ten Cate H +1 more
TL;DR: Bleeding may be the presenting symptom in a patient with disseminated intravascular coagulation, a factor that can complicate decisions about treatment, and the use and subsequent depletion of platelets and coagulating proteins resulting from the ongoing coagulations may induce severe bleeding.
Journal ArticleDOI
Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer
Steven E. Raper,Narendra Chirmule,Frank S. Lee,Nelson A. Wivel,Adam Bagg,Guangping Gao,James M. Wilson,Mark L. Batshaw +7 more
TL;DR: The death of an 18-year-old male with partial ornithine transcarbamylase (OTC) deficiency who participated in a pilot (safety) study of gene therapy points to the limitations of animal studies in predicting human responses, the steep toxicity curve for replication defective adenovirus vectors, substantial subject-to-subject variation in host responses to systemically administered vectors, and the need for further study of the immune response to these vectors.
Journal ArticleDOI
High-Dose Antithrombin III in Severe Sepsis: A Randomized Controlled Trial
Brian Warren,Alain Eid,Pierre Singer,Subramanion S. Pillay,Peder Carl,Ivan Novak,Pavel Chalupa,Alan Atherstone,Istvan Pénzes,Andrezej Kübler,Sigurd Knaub,Heinz-Otto Keinecke,Hubert Heinrichs,Fritz Schindel,Mathias Juers,Roger C. Bone,Steven M. Opal +16 more
TL;DR: High-dose antithrombin III therapy had no effect on 28-day all-cause mortality in adult patients with severe sepsis and septic shock when administered within 6 hours after the onset and was associated with an increased risk of hemorrhage when administered with heparin.
Journal ArticleDOI
Treatment of Septic Shock with the Tumor Necrosis Factor Receptor:Fc Fusion Protein
Charles J. Fisher,Jan M. Agosti,Steven M. Opal,Stephen F. Lowry,Robert A. Balk,Jerald C. Sadoff,Edward Abraham,Roland M. H. Schein,Ernest Benjamin +8 more
TL;DR: In patients with septic shock, treatment with the TNFR:Fc fusion protein does not reduce mortality, and higher doses appear to be associated with increased mortality.
Journal ArticleDOI
Veno-occlusive Disease of the Liver and Multiorgan Failure after Bone Marrow Transplantation: A Cohort Study of 355 Patients
George B. McDonald,Mary S. Hinds,Lloyd D. Fisher,Howard G. Schoch,John L. Wolford,Banaji M,Barbara J. Hardin,Howard M. Shulman,Reginald A. Clift +8 more
TL;DR: The clinical impression is that the current incidence of VOD at the institution is much higher than the 21% rate reported 9 years ago and that more patients have severe liver disease, which may explain the apparent increased incidence and severity of this complication.
References
More filters
Journal ArticleDOI
Shock and tissue injury induced by recombinant human cachectin.
Kevin J. Tracey,Bruce Beutler,Stephen F. Lowry,James P Merryweather,Stephen D. Wolpe,Ian W. Milsark,Robert J. Hariri,Thomas J. Fahey,Alejandro Zentella,J. D. Albert,G. Tom Shires,Anthony Cerami +11 more
TL;DR: It appears that a single protein mediator (cachectin) is capable of inducing many of the deleterious effects of endotoxin.
Journal ArticleDOI
Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia
Kevin J. Tracey,Kevin J. Tracey,Yuman Fong,David G. Hesse,Kirk R. Manogue,Annette T. Lee,George C. Kuo,Stephen F. Lowry,Anthony Cerami +8 more
TL;DR: Protection against shock, vital organ dysfunction, persistent stress hormone release and death was conferred by administration of antibodies 2 h before bacterial infusion, indicating that cachectin is a mediator of fatal bacteraemic shock and suggesting that antibodies against Cachectin offer a potential therapy of life-threatening infection.
Journal ArticleDOI
Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin
TL;DR: The data suggest that cachectin/TNF is one of the principal mediators of the lethal effect of endotoxin, and this effect was dose-dependent and was most effective when the antiserum was administered prior to the injection of the endotoxin.
Journal ArticleDOI
Detection of circulating tumor necrosis factor after endotoxin administration.
Hamish R. Michie,Kirk R. Manogue,David R. Spriggs,Arthur Revhaug,S. T. O'Dwyer,Charles A. Dinarello,Anthony Cerami,Sheldon M. Wolff,Douglas W. Wilmore +8 more
TL;DR: It is concluded that the response to endotoxin is associated with a brief pulse of circulating tumor necrosis factor and that the resultant responses are effected through the cyclooxygenase pathway.
Journal ArticleDOI
Cachectin: more than a tumor necrosis factor.
Bruce Beutler,Anthony Cerami +1 more
TL;DR: The metabolic impact of infectious and neoplastic disease states has long been known to clinicians and may provoke a severe wasting diathesis, in which negative calorie and nitrogen balance lead to death despite the absence of a large parasite or tumor burden.
Related Papers (5)
Modulation of endothelial cell hemostatic properties by tumor necrosis factor.
Peter P. Nawroth,David M. Stern +1 more