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The effects of argatroban on thrombin generation and hemostatic activation in vitro.

Publication ,  Journal Article
Tanaka, KA; Szlam, F; Katori, N; Sato, N; Vega, JD; Levy, JH
Published in: Anesth Analg
November 2004

We evaluated argatroban, a direct thrombin inhibitor, as a heparin adjunct for anticoagulation. Platelet-poor plasma (PPP) was isolated from blood collected from 12 volunteers. Thrombin generation measurements were performed in donor PPP that was mixed with antithrombin (AT)-poor plasma to yield AT levels of 0%, 20%, 60%, and 100%. Effects of argatroban (0-1.0 microg/mL), heparin (0.25 U/mL), or the combination of argatroban (0.5 microg/mL) and heparin were also studied. The addition of increasing concentrations of argatroban, heparin, or both to donor PPP (AT level approximately 100%) caused progressive decreases in the lag time and peak formation of thrombin generation. Heparin (0.25 U/mL) at small AT concentrations had a minimal effect on lag time or peak thrombin formation; its effectiveness of inhibiting thrombin was directly correlated with the concentration of AT. Argatroban at 0.5 microg/mL was effective in decreasing thrombin formation at both low and normal AT levels, but it was most effective when combined with heparin. Additionally, blood samples were obtained from 47 cardiac surgical patients, and the interaction of heparin (>1.5 U/mL) and AT or argatroban on clot formation was evaluated with kaolin activated clotting times (ACTs). Significant increases of ACTs at all heparin levels were observed with the addition of argatroban (0.125 and 0.25 microg/mL). The addition of AT (0.2 U/mL) to heparinized blood samples further prolonged ACTs. In summary, we showed that argatroban, unlike heparin, could effectively reduce thrombin generation regardless of AT levels and could prolong ACTs in vitro at clinically used concentrations.

Duke Scholars

Published In

Anesth Analg

DOI

ISSN

0003-2999

Publication Date

November 2004

Volume

99

Issue

5

Start / End Page

1283 / 1289

Location

United States

Related Subject Headings

  • Whole Blood Coagulation Time
  • Thrombin
  • Sulfonamides
  • Serine Proteinase Inhibitors
  • Platelet Count
  • Pipecolic Acids
  • Partial Thromboplastin Time
  • Middle Aged
  • Male
  • International Normalized Ratio
 

Citation

APA
Chicago
ICMJE
MLA
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Tanaka, K. A., Szlam, F., Katori, N., Sato, N., Vega, J. D., & Levy, J. H. (2004). The effects of argatroban on thrombin generation and hemostatic activation in vitro. Anesth Analg, 99(5), 1283–1289. https://doi.org/10.1213/01.ANE.0000134685.75813.EB
Tanaka, Kenichi A., Fania Szlam, Nobuyuki Katori, Nobukazu Sato, J David Vega, and Jerrold H. Levy. “The effects of argatroban on thrombin generation and hemostatic activation in vitro.Anesth Analg 99, no. 5 (November 2004): 1283–89. https://doi.org/10.1213/01.ANE.0000134685.75813.EB.
Tanaka KA, Szlam F, Katori N, Sato N, Vega JD, Levy JH. The effects of argatroban on thrombin generation and hemostatic activation in vitro. Anesth Analg. 2004 Nov;99(5):1283–9.
Tanaka, Kenichi A., et al. “The effects of argatroban on thrombin generation and hemostatic activation in vitro.Anesth Analg, vol. 99, no. 5, Nov. 2004, pp. 1283–89. Pubmed, doi:10.1213/01.ANE.0000134685.75813.EB.
Tanaka KA, Szlam F, Katori N, Sato N, Vega JD, Levy JH. The effects of argatroban on thrombin generation and hemostatic activation in vitro. Anesth Analg. 2004 Nov;99(5):1283–1289.

Published In

Anesth Analg

DOI

ISSN

0003-2999

Publication Date

November 2004

Volume

99

Issue

5

Start / End Page

1283 / 1289

Location

United States

Related Subject Headings

  • Whole Blood Coagulation Time
  • Thrombin
  • Sulfonamides
  • Serine Proteinase Inhibitors
  • Platelet Count
  • Pipecolic Acids
  • Partial Thromboplastin Time
  • Middle Aged
  • Male
  • International Normalized Ratio