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Evaluation of a novel kallikrein inhibitor on hemostatic activation in vitro.

Publication ,  Journal Article
Tanaka, KA; Szlam, F; Katori, N; Vega, JD; Levy, JH
Published in: Thromb Res
2004

BACKGROUND: DX-88 is a potent kallikrein inhibitor that is being studied for the treatment of hereditary angioedema (HAE) and represents a potential alternative to aprotinin in cardiac surgical patients. The current study was designed to evaluate in vitro effects of DX-88 on coagulation in comparison with aprotinin. METHODS: Blood samples were obtained from consented 12 healthy volunteers. DX-88 or aprotinin was added to blood at 200 and 800 kallikrein inhibitory units (KIU) per milliliter for aprotinin, and at 1.1, 2.2, or 8.8 microg/ml for DX-88. Thromboelastography (TEG) was performed using celite, kaolin, or tissue factor (TF) activation. Kaolin-based activated clotting times (ACTs) were measured at different heparin levels. The whole blood prothrombin time (PT)/PTT values were also measured. The endogenous thrombin generation was assessed with a fluorogenic assay using platelet-poor plasma (PPP). RESULTS: With celite and kaolin activation of TEG, the reaction time was prolonged with DX-88 and aprotinin. With tissue factor activation, TEG parameters were not affected. DX-88 caused dose-dependent kaolin-ACT prolongation that was augmented by increasing doses of heparin. DX-88 or aprotinin had no significant effects on the PT values, but PTT values were dose-dependently prolonged. Both agents delayed the onset of thrombin generation when PTT reagent was used as a trigger, whereas no change was observed when tissue factor was used. CONCLUSION: We found that DX-88 delayed contact activator induced coagulation without affecting tissue factor mediated coagulation. For evaluation of coagulation during DX-88 therapy, the use of PT or tissue factor-activated TEG may be preferable.

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Published In

Thromb Res

DOI

ISSN

0049-3848

Publication Date

2004

Volume

113

Issue

5

Start / End Page

333 / 339

Location

United States

Related Subject Headings

  • Whole Blood Coagulation Time
  • Thrombin
  • Thrombelastography
  • Recombinant Proteins
  • Prothrombin Time
  • Partial Thromboplastin Time
  • Oligopeptides
  • Kallikreins
  • In Vitro Techniques
  • Humans
 

Citation

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Tanaka, K. A., Szlam, F., Katori, N., Vega, J. D., & Levy, J. H. (2004). Evaluation of a novel kallikrein inhibitor on hemostatic activation in vitro. Thromb Res, 113(5), 333–339. https://doi.org/10.1016/j.thromres.2004.03.022
Tanaka, Kenichi A., Fania Szlam, Nobuyuki Katori, J David Vega, and Jerrold H. Levy. “Evaluation of a novel kallikrein inhibitor on hemostatic activation in vitro.Thromb Res 113, no. 5 (2004): 333–39. https://doi.org/10.1016/j.thromres.2004.03.022.
Tanaka KA, Szlam F, Katori N, Vega JD, Levy JH. Evaluation of a novel kallikrein inhibitor on hemostatic activation in vitro. Thromb Res. 2004;113(5):333–9.
Tanaka, Kenichi A., et al. “Evaluation of a novel kallikrein inhibitor on hemostatic activation in vitro.Thromb Res, vol. 113, no. 5, 2004, pp. 333–39. Pubmed, doi:10.1016/j.thromres.2004.03.022.
Tanaka KA, Szlam F, Katori N, Vega JD, Levy JH. Evaluation of a novel kallikrein inhibitor on hemostatic activation in vitro. Thromb Res. 2004;113(5):333–339.
Journal cover image

Published In

Thromb Res

DOI

ISSN

0049-3848

Publication Date

2004

Volume

113

Issue

5

Start / End Page

333 / 339

Location

United States

Related Subject Headings

  • Whole Blood Coagulation Time
  • Thrombin
  • Thrombelastography
  • Recombinant Proteins
  • Prothrombin Time
  • Partial Thromboplastin Time
  • Oligopeptides
  • Kallikreins
  • In Vitro Techniques
  • Humans