Table 1.
The warfarin decay model: (A) reaction; (B) species; (C) species half-lives.
| (A) REACTIONS IN THE WARFARIN DECAY MODEL | ||
|---|---|---|
| Reaction name | Stoichiometry | Kinetics |
| RfII–decay | fII → inactive species* | fII × ln(2)/t½ fII |
| RfII–formation | Profactor* → fII | (kfII × ln(2)/t½ fII)/(formation rate + 1) |
| RfIX–decay | fIX → inactive species* | fIX × ln(2)/t½ fIX |
| RfIX–formation | Profactor* → fIX | (kfIX × ln(2)/t½ fIX)/(formation rate + 1) |
| RfVII–decay | fVII → inactive species* | fVII × ln(2)/t½ fVII |
| RfVII–formation | Profactor* → fVII | (kfVII × ln(2)/t½ fVII)/(formation rate + 1) |
| R-warfarin–decay | R-warfarin → inactive species* | R-warfarin × ln(2)/t½ R-warfarin |
| S-warfarin–decay | S-warfarin → inactive species* | S-warfarin × ln(2)/t½ S-warfarin |
| RfX–decay | fX → inactive species* | fX × ln(2)/t½ fX |
| RfX–formation | Profactor* → fX | (kfX × ln(2)/t½ fX)/(formation rate + 1) |
| Protein C–decay | Protein C → inactive species* | Protein C × ln(2)/t½ Protein C |
| Protein C–formation | Profactor* → Protein C | (kProtein C × ln(2)/t½ Protein C)/(formation rate + 1) |
| Protein S–decay | Protein S → inactive species* | Protein S × ln(2)/t½ Protein S |
| Protein S–formation | Profactor* → Protein S | (kProtein S × ln(2)/t½ Protein S)/(formation rate + 1) |
| (B) KEY PARTICIPANTS IN THE WARFARIN DECAY MODEL | ||
| Species | Initial concentration (M) | |
| fII | 1.40 × 10−6 | |
| fIX | 9.00 × 10−8 | |
| fVII | 1.00 × 10−8 | |
| Effective R-warfarin/ S-warfarin* | Fitted to obtain start INR | |
| fX | 1.60 × 10−7 | |
| Protein C | 6.00 × 10−8 | |
| Protein S | 1.40 × 10−7 | |
| Protein C/S binding sites on phospholipids | 3.60 × 10−6 | |
| (C) TYPICAL HALF-LIFE (t½) FOR SPECIES IN THE WARFARIN DECAY MODEL | ||
| Species (half-life) | Time (s) | |
| t½ fII | 205,200 (57 h) | |
| t½ fIX | 91,800 (25.5 h) | |
| t½ fVII | 18,000 (5 h) | |
| t½ fX | 135,000 (37.5 h) | |
| t½ protein C | 32,400 (9 h) | |
| t½ protein S | 216,000 (60 h) | |
| t½ R-warfarin | 162,000 | |
| t½ S-warfarin | 104,400† | |
Note for Table A: For the calculation of the formation rate, see section on Turnover model for vitamin K-dependent coagulation factors in the Materials and Methods.
Indicates a ‘boundary species’ that has its value kept constant during the simulation. f, Factor; k, kinetic rate constant; R, reaction; t½, half-life.
Note for Table B:
Effective R-warfarin and S-warfarin concentrations are in arbitrary units reflecting the fraction of remaining warfarin.
Factor concentrations (II, VII, IX, X) are average plasma concentrations taken from Hockin et al. (2002). Protein C and S concentrations were taken from Bungay et al. (2003); protein S was corrected to reflect the free plasma concentration (40% of total) reported in the protein C monograph available online at www.chromogenix.com. f, Factor; INR, international normalized ratio.
Note for Table C:
74,897 for Japanese patients. f, Factor.