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Anti-factor IXa Aptamer reduces propagation of thrombin generation in plasma anticoagulated with warfarin.

Publication ,  Journal Article
Szlam, F; Luan, D; Bolliger, D; Szlam, AD; Levy, JH; Varner, JD; Tanaka, KA
Published in: Thromb Res
May 2010

BACKGROUND: Warfarin is routinely used in the prevention and treatment of prothrombotic events. During initiation of warfarin therapy levels of factor (F) VII and protein C decrease rapidly but prothrombin, FIX and FX decline much slower. Therefore, propagation of thrombin generation (TG) remains unaffected much longer, increasing the risk of inadequate anticoagulation. Recently, a novel agent, anti-IXa aptamer, RB006, has been developed. Therefore, we have evaluated the in vitro effects of this agent in warfarin plasma. METHODS: The investigation consisted of two parts. First, a computer simulated time course of TG with warfarin alone and in combination with FIXa inhibition was evaluated and, second, normal volunteer, protein C deficient, FVII deficient and commercial warfarin plasmas (INR 2.1 and 3.1) were spiked with increasing concentrations of aptamer (0-24 microg/ml) and its anticoagulant effects were evaluated using prothrombin time (PT), activated partial thromboplastin time (aPTT) and TG with tissue factor and Actin as activators. Direct effects of aptamer on protein C were also evaluated. RESULTS: Simulation of coagulation during warfarin induction showed that TG can be significantly delayed and decreased by inhibiting FIXa (i.e., with anti-FIXa aptamer). The anti-FIXa aptamer inhibited TG in all tested plasmas, but was most efficacious in warfarin and FVII deficient plasma. The aptamer itself did not inhibit protein C and had no effect on PT, but concentration-dependently increased aPTT. CONCLUSION: The anti-FIXa aptamer potentiates the inhibitory effects of warfarin on TG, and may fill the need as an adjuvant agent during initiation of warfarin therapy.

Duke Scholars

Published In

Thromb Res

DOI

EISSN

1879-2472

Publication Date

May 2010

Volume

125

Issue

5

Start / End Page

432 / 437

Location

United States

Related Subject Headings

  • Warfarin
  • Thrombin
  • Plasma
  • Humans
  • Factor IXa
  • Drug Combinations
  • Dose-Response Relationship, Drug
  • Cardiovascular System & Hematology
  • Aptamers, Nucleotide
  • Anticoagulants
 

Citation

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ICMJE
MLA
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Szlam, F., Luan, D., Bolliger, D., Szlam, A. D., Levy, J. H., Varner, J. D., & Tanaka, K. A. (2010). Anti-factor IXa Aptamer reduces propagation of thrombin generation in plasma anticoagulated with warfarin. Thromb Res, 125(5), 432–437. https://doi.org/10.1016/j.thromres.2009.11.018
Szlam, Fania, Deyan Luan, Daniel Bolliger, Arthur D. Szlam, Jerrold H. Levy, Jeffrey D. Varner, and Kenichi A. Tanaka. “Anti-factor IXa Aptamer reduces propagation of thrombin generation in plasma anticoagulated with warfarin.Thromb Res 125, no. 5 (May 2010): 432–37. https://doi.org/10.1016/j.thromres.2009.11.018.
Szlam F, Luan D, Bolliger D, Szlam AD, Levy JH, Varner JD, et al. Anti-factor IXa Aptamer reduces propagation of thrombin generation in plasma anticoagulated with warfarin. Thromb Res. 2010 May;125(5):432–7.
Szlam, Fania, et al. “Anti-factor IXa Aptamer reduces propagation of thrombin generation in plasma anticoagulated with warfarin.Thromb Res, vol. 125, no. 5, May 2010, pp. 432–37. Pubmed, doi:10.1016/j.thromres.2009.11.018.
Szlam F, Luan D, Bolliger D, Szlam AD, Levy JH, Varner JD, Tanaka KA. Anti-factor IXa Aptamer reduces propagation of thrombin generation in plasma anticoagulated with warfarin. Thromb Res. 2010 May;125(5):432–437.
Journal cover image

Published In

Thromb Res

DOI

EISSN

1879-2472

Publication Date

May 2010

Volume

125

Issue

5

Start / End Page

432 / 437

Location

United States

Related Subject Headings

  • Warfarin
  • Thrombin
  • Plasma
  • Humans
  • Factor IXa
  • Drug Combinations
  • Dose-Response Relationship, Drug
  • Cardiovascular System & Hematology
  • Aptamers, Nucleotide
  • Anticoagulants