scholarly journals In vitro uptake of recombinant factor VIIa by megakaryocytes with subsequent production of platelets containing functionally active drug

2016 ◽  
Vol 178 (3) ◽  
pp. 482-486 ◽  
Author(s):  
Anne Marieke Schut ◽  
Marc Kirschbaum ◽  
Jelle Adelmeijer ◽  
Philip G. de Groot ◽  
Ton Lisman
Keyword(s):  
Active Drug ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
In Vitro Uptake

scholarly journals Management of the Bleeding Patient Receiving New Oral Anticoagulants: A Role for Prothrombin Complex Concentrates

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Lisa M. Baumann Kreuziger ◽  
Joseph C. Keenan ◽  
Colleen T. Morton ◽  
David J. Dries
Keyword(s):  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Oral Anticoagulants ◽  
New Oral Anticoagulants ◽  
Coagulation Cascade ◽  
Clotting Factors ◽  
Prothrombin Complex Concentrates ◽  
Clotting System ◽  
Clinical Trial Evidence

Ease of dosing and simplicity of monitoring make new oral anticoagulants an attractive therapy in a growing range of clinical conditions. However, newer oral anticoagulants interact with the coagulation cascade in different ways than traditional warfarin therapy. Replacement of clotting factors will not reverse the effects of dabigatran, rivaroxaban, or apixaban. Currently, antidotes for these drugs are not widely available. Fortunately, withholding the anticoagulant and dialysis are freqnently effective treatments, particularly with rivaroxaban and dabigatran. Emergent bleeding, however, requires utilization of Prothrombin Complex Concentrates (PCCs). PCCs, in addition to recombinant factor VIIa, are used to activate the clotting system to reverse the effects of the new oral anticoagulants. In cases of refractory or emergent bleeding, the recommended factor concentrate in our protocols differs between the new oral anticoagulants. In patients taking dabigatran, we administer an activated PCC (aPCC) [FELBA] due to reported benefit in human in vitro studies. Based on human clinical trial evidence, the 4-factor PCC (Kcentra) is suggested for patients with refractory rivaroxaban- or apixaban-associated hemorrhage. If bleeding continues, recombinant factor VIIa may be employed. With all of these new procoagulant agents, the risk of thrombosis associated with administration of factor concentrates must be weighed against the relative risk of hemorrhage.

scholarly journals A Variant of Recombinant Factor VIIa With Enhanced Procoagulant and Antifibrinolytic Activities in an In Vitro Model of Hemophilia

2007 ◽  
Vol 27 (3) ◽  
pp. 683-689 ◽  
Author(s):  
Geoffrey A. Allen ◽  
Egon Persson ◽  
Robert A. Campbell ◽  
Mirella Ezban ◽  
Ulla Hedner ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Vitro Model

Inhibition of fibrinolysis by recombinant factor VIIa in plasma from patients with severe hemophilia A

Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 175-179 ◽  
Author(s):  
Ton Lisman ◽  
Laurent O. Mosnier ◽  
Thierry Lambert ◽  
Evelien P. Mauser-Bunschoten ◽  
Joost C. M. Meijers ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
In Vitro Study ◽  
Clot Lysis ◽  
Severe Hemophilia ◽  
Large Variability ◽  
Lysis Time ◽  
Clot Lysis Time

Recombinant factor VIIa (rFVIIa) is a novel prohemostatic drug for patients with hemophilia who have developed inhibitory antibodies. The postulation has been made that hemophilia is not only a disorder of coagulation, but that hyperfibrinolysis due to a defective activation of thrombin activatable fibrinolysis inhibitor (TAFI) might also play a role. In this in vitro study, the potential of rFVIIa to down-regulate fibrinolysis via activation of TAFI was investigated. rFVIIa was able to prolong clot lysis time in plasmas from 17 patients with severe hemophilia A. The prolongation of clot lysis time by rFVIIa was completely abolished by addition of an inhibitor of activated TAFI. The concentration of rFVIIa required for half maximal prolongation of clot lysis time (Clys½-VIIa) varied widely between patients (median, 73.0 U/mL; range, 10.8-250 U/mL). The concentration of rFVIIa required for half maximal reduction of clotting time (Cclot½-VIIa) was approximately 10-fold lower than the Clys½-VIIa value (median, 8.4 U/mL; range, 1.7-22.5 U/mL). Inhibition of TFPI with a polyclonal antibody significantly decreased Clys½-VIIa values (median, 2.6 U/mL; range, 0-86.9 U/mL), whereas Cclot½-VIIa values did not change (median, 7.2 U/mL; range, 2.2-22.5 U/mL). On addition of 100 ng/mL recombinant full-length TFPI, a nonsignificant increase of Clys½-VIIa values was observed (median, 119.2 U/mL; range, 12.3-375.0 U/mL), whereas Cclot½-VIIa values did not change (median, 8.8 U/mL; range, 2.6-34.6 U/mL). In conclusion, this study shows that rFVIIa both accelerates clot formation and inhibits fibrinolysis by activation of TAFI in factor VIII-deficient plasma. However, a large variability in antifibrinolytic potential of rFVIIa exists between patients.

scholarly journals Activation of Coagulation by Administration of Recombinant Factor VIIa Elicits Interleukin 6 (IL-6) and IL-8 Release in Healthy Human Subjects

2003 ◽  
Vol 10 (3) ◽  
pp. 495-497 ◽  
Author(s):  
Evert de Jonge ◽  
Philip W. Friederich ◽  
George P. Vlasuk ◽  
William E. Rote ◽  
Margaretha B. Vroom ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Interleukin 6 ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Human Subjects ◽  
In Vitro Experiments ◽  
Healthy Human ◽  
Healthy Human Subjects ◽  
Proinflammatory Responses

ABSTRACT The activation of coagulation has been shown to contribute to proinflammatory responses in animal and in vitro experiments. Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma. This increase was absent when the subjects were pretreated with recombinant nematode anticoagulant protein c2, the inhibitor of tissue factor-factor VIIa.

Effect of recombinant factor VIIa (Novoseven[reg ]) on thrombocytopenia-like conditions in vitro

2001 ◽  
Vol 38 (4F) ◽  
pp. 15-20 ◽  
Author(s):  
Marianne Kjalke ◽  
Marie Johannessen ◽  
Ulla Hedner
Keyword(s):  
Recombinant Factor Viia ◽  
Factor Viia

The in vitro effect of recombinant factor VIIa on coated platelet formation and clot dynamics of stored platelet concentrates

Transfusion ◽  
2009 ◽  
Vol 49 (10) ◽  
pp. 2186-2194 ◽  
Author(s):  
Mette S. Svendsen ◽  
Annemarie T. Kristensen ◽  
Louise Bochsen ◽  
José A. Salado-Jimena ◽  
Pär I. Johansson
Keyword(s):  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Platelet Concentrates ◽  
Vitro Effect ◽  
Platelet Formation

The Effect of In Vitro Recombinant Factor VIIA on Coagulation Parameters for Blood Taken During Liver Transplantation

2005 ◽  
Vol 37 (10) ◽  
pp. 4367-4369 ◽  
Author(s):  
B. Gali ◽  
S.R. Rettke ◽  
D.J. Plevak ◽  
G.A. Nuttall ◽  
P.J. Santrach ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Coagulation Parameters

scholarly journals Recombinant factor VIIa reverses the in vitro and ex vivo anticoagulant and profibrinolytic effects of fondaparinux

2003 ◽  
Vol 1 (11) ◽  
pp. 2368-2373 ◽  
Author(s):  
T. Lisman ◽  
N. R. Bijsterveld ◽  
J. Adelmeijer ◽  
J. C. M. Meijers ◽  
M. Levi ◽  
...  
Keyword(s):  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Ex Vivo
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