Thrombin generation and fibrinolysis in anti-factor IX treated blood and plasma spiked with factor VIII inhibitor bypassing activity or recombinant factor VIIa.

Published

Journal Article

Activated prothrombin complex concentrates (aPCC) and recombinant activated factor VIIa (rFVIIa) are two important therapies in haemophilia patients with inhibitors and improve clot stability. We hypothesized that potential differences in procoagulant and fibrinolytic actions of aPCC and rFVIIa may lie in the clot stability against fibrinolytic activation. We used thrombin generation, fluorescence detection and thromboelastometry in anti-factor IXa (FIXa) aptamer-treated whole blood (WB) and plasma to evaluate: (i) generation of thrombin and activated factor X (FXa) and (ii) viscoelastic properties of blood clots in the presence of tissue plasminogen activator (tPA) after addition of aPCC (0.4 U mL(-1)) or rFVIIa (60 nm). Peak thrombin generation increased from 85 +/- 19 nm in aptamer-treated plasma to 276 +/- 83 nm and 119 +/- 22 nm after addition of aPCC and rFVIIa respectively (P < 0.001). FXa activity increased within 20 min by 87 +/- 6% and by 660 +/- 97% after addition of aPCC and rFVIIa respectively (P < 0.001). TPA-induced lysis time increased from 458 +/- 378 s in aptamer-treated WB to 1597 +/- 366 s (P = 0.001) and 1132 +/- 214 s (P = 0.075), after addition of aPCC and rFVIIa respectively. In this haemophilia model using the anti-FIXa aptamer, the larger amount of thrombin was generated with aPCC compared with rFVIIa, while FXa generation was more rapidly increased in the presence of rFVIIa. Furthermore, clot formation in anti-FIXa aptamer-treated WB was less susceptible to tPA-induced fibrinolysis after adding aPCC compared with rFVIIa.

Full Text

Duke Authors

Cited Authors

  • Bolliger, D; Szlam, F; Molinaro, RJ; Escobar, MA; Levy, JH; Tanaka, KA

Published Date

  • May 2010

Published In

Volume / Issue

  • 16 / 3

Start / End Page

  • 510 - 517

PubMed ID

  • 20050927

Pubmed Central ID

  • 20050927

Electronic International Standard Serial Number (EISSN)

  • 1365-2516

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2516.2009.02164.x

Language

  • eng

Conference Location

  • England