Skip to main content

Thrombin-activated thrombelastography for evaluation of thrombin interaction with thrombin inhibitors.

Publication ,  Journal Article
Taketomi, T; Szlam, F; Vinten-Johansen, J; Levy, JH; Tanaka, KA
Published in: Blood Coagul Fibrinolysis
December 2007

For intravenous anticoagulation, heparin has been the mainstay drug, but its use may be contraindicated in heparin-induced thrombocytopenia and thrombosis. Heparin alternatives including direct thrombin inhibitors are available, but clotting assays (e.g. partial thromboplastin time) measure the time required to form fibrin gel when only a small amount of thrombin is generated. It was hypothesized that the extent of thrombin inhibition varies among inhibitors, and thrombin-activated thrombelastography would provide useful data on therapeutic responses to thrombin inhibitors. Thrombin was added (0-100 nmol/l final concentration) to nonrecalcified whole blood to evaluate clot formation on thrombelastography. Effects of direct thrombin inhibitors (argatroban 3.75 microg/ml, bivalirudin 15 microg/ml, and lepirudin 3.0 microg/ml), and heparin cofactor II activator and dermatan disulfate (20 microg/ml) were evaluated in the presence of 100 nmol/l thrombin. The interactions of thrombin and respective inhibitors were also compared by fluorogenic thrombin substrate cleavage. Increasing concentrations of thrombin progressively shortened the lag time and increased viscoelasticity on thrombelastography. Only 20 nmol/l thrombin caused instantaneous clotting, but maximal viscoelastic force was obtained at 50-100 nmol/l thrombin. All thrombin inhibitors prolonged the lag time (lepirudin > bivalirudin > argatroban = dermatan disulfate), but full recovery of thrombelastography viscoelasticity was observed with argatroban and bivalirudin. Lepirudin abrogated clotting, and dermatan disulfate suppressed clot development on thrombelastography. Thrombin substrate cleavage was observed only for bivalirudin, and heparin cofactor II without dermatan disulfate. The modified thrombelastography technique using nonrecalcified whole blood may be useful in evaluating the extent and reversibility of thrombin blockade with direct or indirect thrombin inhibitors.

Duke Scholars

Published In

Blood Coagul Fibrinolysis

DOI

ISSN

0957-5235

Publication Date

December 2007

Volume

18

Issue

8

Start / End Page

761 / 767

Location

England

Related Subject Headings

  • Thrombin
  • Thrombelastography
  • Humans
  • Hirudins
  • Heparin Cofactor II
  • Fibrinolytic Agents
  • Cardiovascular System & Hematology
  • Blood Coagulation
  • Anticoagulants
  • 3202 Clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Taketomi, T., Szlam, F., Vinten-Johansen, J., Levy, J. H., & Tanaka, K. A. (2007). Thrombin-activated thrombelastography for evaluation of thrombin interaction with thrombin inhibitors. Blood Coagul Fibrinolysis, 18(8), 761–767. https://doi.org/10.1097/MBC.0b013e3282f102c6
Taketomi, Taro, Fania Szlam, Jakob Vinten-Johansen, Jerrold H. Levy, and Kenichi A. Tanaka. “Thrombin-activated thrombelastography for evaluation of thrombin interaction with thrombin inhibitors.Blood Coagul Fibrinolysis 18, no. 8 (December 2007): 761–67. https://doi.org/10.1097/MBC.0b013e3282f102c6.
Taketomi T, Szlam F, Vinten-Johansen J, Levy JH, Tanaka KA. Thrombin-activated thrombelastography for evaluation of thrombin interaction with thrombin inhibitors. Blood Coagul Fibrinolysis. 2007 Dec;18(8):761–7.
Taketomi, Taro, et al. “Thrombin-activated thrombelastography for evaluation of thrombin interaction with thrombin inhibitors.Blood Coagul Fibrinolysis, vol. 18, no. 8, Dec. 2007, pp. 761–67. Pubmed, doi:10.1097/MBC.0b013e3282f102c6.
Taketomi T, Szlam F, Vinten-Johansen J, Levy JH, Tanaka KA. Thrombin-activated thrombelastography for evaluation of thrombin interaction with thrombin inhibitors. Blood Coagul Fibrinolysis. 2007 Dec;18(8):761–767.

Published In

Blood Coagul Fibrinolysis

DOI

ISSN

0957-5235

Publication Date

December 2007

Volume

18

Issue

8

Start / End Page

761 / 767

Location

England

Related Subject Headings

  • Thrombin
  • Thrombelastography
  • Humans
  • Hirudins
  • Heparin Cofactor II
  • Fibrinolytic Agents
  • Cardiovascular System & Hematology
  • Blood Coagulation
  • Anticoagulants
  • 3202 Clinical sciences