ArticleThrombosis research2011
Recombinant factor VIIa analog NN1731 (V158D/E296V/M298Q-FVIIa) enhances fibrin formation, structure and stability in lipidated hemophilic plasma.
Article in Thrombosis research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
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- Clot formation and fibrinolysis assays reveal functional differences among hemostatic agents in hemophilia A plasma.Research and practice in thrombosis and haemostasis · 2024Article
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- Article
- Tissue factor pathway inhibitor is a potential modifier of bleeding risk in factor XI deficiency.Journal of thrombosis and haemostasis : JTH · 2023Article
- A proposal for managing bleeding in patients on therapeutic factor XI(a) inhibitors.Journal of thrombosis and haemostasis : JTH · 2022Article
- Fibrinolysis and bleeding of unknown cause.Research and practice in thrombosis and haemostasis · 2021Article
- Thrombin-generating potential, plasma clot formation, and clot lysis are impaired in patients with bleeding of unknown cause.Journal of thrombosis and haemostasis : JTH · 2019Article
- Abnormal plasma clot formation and fibrinolysis reveal bleeding tendency in patients with partial factor XI deficiency.Blood advances · 2018Article
- Coagulation activation in sickle cell trait: an exploratory study.British journal of haematology · 2015Article
- Fibrinolysis and the control of blood coagulation.Blood reviews · 2015Review
- Air pollution upregulates endothelial cell procoagulant activity via ultrafine particle-induced oxidant signaling and tissue factor expression.Toxicological sciences : an official journal of the Society of Toxicology · 2014Article
- Abnormal plasma clot structure and stability distinguish bleeding risk in patients with severe factor XI deficiency.Journal of thrombosis and haemostasis : JTH · 2014Article
- Optical imaging of fibrin deposition to elucidate participation of mast cells in foreign body responses.Biomaterials · 2014Article
- Effect of BAX499 aptamer on tissue factor pathway inhibitor function and thrombin generation in models of hemophilia.Thrombosis research · 2012Article
- Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
introductionThe bypassing agent recombinant factor VIIa (rFVIIa) is efficacious in treating bleeding in hemophilia patients with inhibitors. Efforts have focused on the rational engineering of rFVIIa variants with increased hemostatic potential. One rFVIIa analog (V158D/E296V/M298Q-FVIIa, NN1731) improves thrombin generation and clotting in purified systems, whole blood from hemophilic patients and factor VIII-deficient mice.
methodsWe used calibrated automated thrombography and plasma clotting assays to compare effects of bypassing agents (rFVIIa, NN1731) on hemophilic clot formation, structure, and ability to resist fibrinolysis.
resultsBoth rFVIIa and NN1731 shortened the clotting onset and increased the maximum rate of fibrin formation and fibrin network density in hemophilic plasma clots. In the presence of tissue plasminogen activator, both rFVIIa and NN1731 shortened the time to peak turbidity (TTPeak(tPA)) and increased the area under the clot formation curve (AUC(tPA)). Phospholipids increased both rFVIIa and NN1731 activity in a lipid concentration-dependent manner. Estimated geometric mean concentrations of rFVIIa and NN1731 producing similar onset, rate, TTPeak(tPA), and AUC(tPA) as seen with 100% factors VIII and IX were: 24.5, 74.3, 29.7, and 37.1 nM rFVIIa, and 8.6, 31.2, 9.0, and 11.3 nM NN1731, respectively. In each case, the NN1731 concentration was significantly lower than rFVIIa.
conclusionsThese findings suggest that like rFVIIa, NN1731 improves the formation, structure, and stability of hemophilic clots. Higher lipid concentrations may facilitate assessment of both rFVIIa and NN1731 activity. NN1731 appears likely to support rapid clot formation in tissues with high endogenous fibrinolytic activity.
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