Thrombin generation by activated factor VII on platelet activated by different agonists. Extending the cell-based model of hemostasis

被引：19

作者：

Altman R. ^{[1
]}

Scazziota A.S. ^{[1
]}

Herrera M. de L. ^{[1
]}

Gonzalez C. ^{[2
]}

机构：

[1] Centro de Trombosis de Buenos Aires, Buenos Aires

[2] Department of Pharmacology, School of Medicine, University of Buenos Aires, Buenos Aires

来源：

Thrombosis Journal | / 4卷 / 1期

关键词：

Arachidonic Acid; Thrombin; Tissue Factor; Platelet Rich Plasma; Thrombin Generation;

D O I：

10.1186/1477-9560-4-5

中图分类号：

学科分类号：

摘要：

Background: Platelet activation is crucial in normal hemostasis. Using a clotting system free of external tissue factor, we investigated whether activated Factor VII in combination with platelet agonists increased thrombin generation (TG) in vitro. Methods and results: TG was quantified by time parameters: lag time (LT) and time to peak (TTP), and by amount of TG: peak of TG (PTG) and area under thrombin formation curve after 35 minutes (AUC→ 35min) in plasma from 29 healthy volunteers using the calibrated automated thrombography (CAT) technique. TG parameters were measured at basal conditions and after platelet stimulation by sodium arachidonate (AA), ADP, and collagen (Col). In addition, the effects of recombinant activated FVII (rFVIIa) alone or combined with the other platelet agonists on TG parameters were investigated. We found that LT and TTP were significantly decreased (p < 0.05) and PTG and AUC→35min were significantly increased (p < 0.05) in platelet rich plasma activated with AA, ADP, Col, and rFVIIa compared to non-activated platelet rich plasma from normal subjects (p = 0.01). Furthermore platelet rich plasma activated by the combined effects of rFVIIa plus AA, ADP or Col had significantly reduced LT and TTP and increased AUC→35min (but not PTG) when compared to platelet rich plasma activated with agonists in the absence of rFVIIa. Conclusion: Platelets activated by AA, ADP, Col or rFVIIa triggered TG. This effect was increased by combining rFVIIa with other agonists. Our intrinsic coagulation system produced a burst in TG independent of external tissue factor activity an apparent hemostatic effect with little thrombotic capacity. Thus we suggest a modification in the cell-based model of hemostasis. © 2006 Altman et al; licensee BioMed Central Ltd.

引用

共 27 条

[1] Friederich P.W., Levi M., Bauer K.A., Vlasuk G.P., Rote W.E., Breederveld D., Keller T., Spataro M., Barzegar S., Buller H.R., Ability of recombinant factor VIIa to generate thrombin during inhibition of tissue factor in human subjects, Circulation, 103, pp. 2555-2559, (2001)
[2] Monroe D.M., Hoffman M., Oliver J.A., Roberts H.R., A possible mechanism of action of activated factor VII independent of tissue factor, Blood Coagul Fibrinolysis, 9, SUPPL. 1, (1998)
[3] Zwaal R.F., Comfurius P., Bevers E.M., Lipid-protein interactions in blood coagulation, Biochim Biophys Acta, 1376, pp. 433-453, (1998)
[4] Lentz B.R., Exposure of platelet membrane phosphatidylserine regulates blood coagulation, Prog Lipid Res, 42, pp. 423-438, (2003)
[5] Ross R., Atherosclerosis-An inflammatory disease, N Eng J Med, 340, pp. 115-126, (1999)
[6] Altman R., Scazziota A., Rouvier J., Gonzalez C., Effect of sodium arachidonate on thrombin generation through platelet activation - Inhibitory effect of aspirin, Thromb Haemost, 84, pp. 1109-1112, (2000)
[7] van der Meijden P.E., Feijge M.A., Giesen P.L., Huijberts M., van Raak L.P., Heemskerk J.W., Platelet P2Y12 receptors enhance signalling towards procoagulant activity and thrombin generation A study with healthy subjects and patients at thrombotic risk, Thromb Haemost, 93, pp. 1128-1136, (2005)
[8] Camera M., Frigerio M., Toschi V., Brambilla M., Rossi F., Cottell D.C., Maderna P., Parolari A., Bonzi R., De Vincenti O., Tremoli E., Platelet activation induces cell-surface immunoreactive tissue factor expression, which is modulated differently by antiplatelet drugs, Arterioscler Thromb Vasc Biol, 23, pp. 1690-1696, (2003)
[9] Mackman N., Role of Tissue Factor in Hemostasis, Thrombosis, and Vascular Development, Arterioscler Thromb Vasc Biol, 24, pp. 1015-1022, (2004)
[10] Hemker H.C., Giesen P., Aldieri R., Regnault V., de Smed E., Wagenvoord R., Lecompte T., Beguin S., The calibrated automated thrombogram (CAT): A universal routine test for hyper- and hypocoagulability, Pathophysiol Haemost Thromb, 32, pp. 249-253, (2002)

← 1 2 3 →