Journal of thrombosis and haemostasis : JTH · 2013
A new regulatory function of activated factor V: inhibition of the activation by tissue factor/factor VII(a) of factor X.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Al Dieri R, Bloemen S, Kelchtermans H, Wagenvoord R, Hemker H C
Аннотация
BACKGROUND: We observed that minute amounts of thrombin or the enzyme Russell's viper venom activating factor V (RVV-V) added to plasma strongly diminish the potential of that plasma to generate thrombin after being triggered by tissue factor.
OBJECTIVE: To find the mechanism behind this phenomenon.
METHODS AND RESULTS: Thrombin generation (TG) initiated by tissue factor (TF) is strongly and dose-dependently inhibited by addition of activated factor V (FVa) or by addition of a factor V activator (thrombin or RVV-V). No inhibition is seen when TG is triggered via the intrinsic pathway or by direct activation of factor X. The effect is independent of proteins C and S and tissue factor pathway inhibitor (TFPI). In factor VII-deficient plasma the effect is seen when it is spiked with recombinant factor VII (FVII) and to a much lesser extent when spiked with recombinant FVIIa. In a purified system, FVa also dose-dependently inhibits the activation of FX by TF/FVII(a). The inhibitory effect is neutralized by antibodies against the light chain of FVa but not by antibodies against the heavy chain.
CONCLUSIONS: Our observations can be explained by assuming that FVa, via its light chain, binds to the complex TF/FVII(a) and prevents it from activating FX. We assume that this mechanism reduces the possibility that thrombin and factor Xa escaping from a wound area into the circulation, together with blood-borne tissue factor, would trigger intravascular coagulation.
OBJECTIVE: To find the mechanism behind this phenomenon.
METHODS AND RESULTS: Thrombin generation (TG) initiated by tissue factor (TF) is strongly and dose-dependently inhibited by addition of activated factor V (FVa) or by addition of a factor V activator (thrombin or RVV-V). No inhibition is seen when TG is triggered via the intrinsic pathway or by direct activation of factor X. The effect is independent of proteins C and S and tissue factor pathway inhibitor (TFPI). In factor VII-deficient plasma the effect is seen when it is spiked with recombinant factor VII (FVII) and to a much lesser extent when spiked with recombinant FVIIa. In a purified system, FVa also dose-dependently inhibits the activation of FX by TF/FVII(a). The inhibitory effect is neutralized by antibodies against the light chain of FVa but not by antibodies against the heavy chain.
CONCLUSIONS: Our observations can be explained by assuming that FVa, via its light chain, binds to the complex TF/FVII(a) and prevents it from activating FX. We assume that this mechanism reduces the possibility that thrombin and factor Xa escaping from a wound area into the circulation, together with blood-borne tissue factor, would trigger intravascular coagulation.