Improvement of spatial fibrin formation by the anti‐TFPI aptamer BAX499: changing clot size by targeting extrinsic pathway initiation

Abstract

BAX499 significantly improves spatial coagulation by inhibiting TFPI in a spatially localized manner that is different to that observed with rVIIa.

Gla-domainless factor Xa: molecular bait to bypass a blocked tenase complex

“…More recently, two different kinds of TFPI inhibitors have been investigated: sulfated polysaccharides 16,19 and aptamers. 17,18 Our study, using a strategy to inhibit TFPI that differs from the three previously published methods, confirms the potential interest of this target with regards to restoring blood clotting in hemophilia patients with or without inhibitors.…”

“…15 In addition, other approaches to neutralizing TFPI have been shown to be active ex vivo and in animal models. [16][17][18][19] Here, we propose a new approach to unlock the tenase complex of hemophilia patients with or without inhibitor. In contrast to activated factor X (FXa), Gla-domainless FXa (GDXa) is unable to bind to procoagulant phospholipids and is almost completely devoid of procoagulant activity.…”

Factor XI and traveling waves: the key to understanding coagulation in hemophilia?

“…Specifically, experiments with existing bypassing agents [17] and potential new ones [18] indicate that this should be kept in mind: thrombin produced near activation site is not equivalent to that produced far from it. The 'spatial' concept can provide a new point-of-view for understanding the bleeding mechanism and hemophilia treatment strategies.…”

Influence of temperature on spatial fibrin clot formation process in thrombodynamics

“…Стационарная скорость роста сгустка достоверно не изменилась и при понижении температуры с 37°С до 28°С (p<0,05 непарный критерий Стъюдента). Как было показано ранее [19,20], начальная скорость роста сгустка определяется, главный образом, активностью внешней теназы. В настоящей работе мы исследовали температурную зависимость активности внешней теназы (рис.…”

“…Как было показано ранее [19,20], начальная скорость роста сгустка определяется активностью комплекса внешней теназы, а стационарная скорость роста сгустка -активностью комплекса внутренней теназы, поэтому было принято решение измерить зависимости активностей комплексов внешней и внутренней теназ от температуры.…”