A novel, rapid method to compare the therapeutic windows of oral anticoagulants using the Hill coefficient

Sci Rep. 2016 Jul 21;6:29387. doi: 10.1038/srep29387.


A central challenge in designing and administering effective anticoagulants is achieving the proper therapeutic window and dosage for each patient. The Hill coefficient, nH, which measures the steepness of a dose-response relationship, may be a useful gauge of this therapeutic window. We sought to measure the Hill coefficient of available anticoagulants to gain insight into their therapeutic windows. We used a simple fluorometric in vitro assay to determine clotting activity in platelet poor plasma after exposure to various concentrations of anticoagulants. The Hill coefficient for argatroban was the lowest, at 1.7 ± 0.2 (95% confidence interval, CI), and the Hill coefficient for fondaparinux was the highest, at 4.5 ± 1.3 (95% CI). Thus, doubling the dose of fondaparinux from its IC50 would decrease coagulation activity by nearly a half, whereas doubling the dose of argatroban from its IC50 would decrease coagulation activity by merely one quarter. These results show a significant variation among the Hill coefficients, suggesting a similar variation in therapeutic windows among anticoagulants in our assay.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Anticoagulants / administration & dosage*
  • Arginine / analogs & derivatives
  • Blood Coagulation
  • Blood Platelets / cytology
  • Blood Platelets / drug effects*
  • Dose-Response Relationship, Drug
  • Fluorometry
  • Fondaparinux
  • Humans
  • Inhibitory Concentration 50
  • Pipecolic Acids / administration & dosage*
  • Plasma / drug effects
  • Polysaccharides / administration & dosage*
  • Sulfonamides
  • Thrombin / chemistry


  • Anticoagulants
  • Pipecolic Acids
  • Polysaccharides
  • Sulfonamides
  • Arginine
  • Thrombin
  • argatroban
  • Fondaparinux