Table 2.
Animal and human studies using factor concentrates to reverse anticoagulant effect of dabigatran, rivaroxaban, and apixaban.
| Author | Reversal agent | Test system | Coagulation test effect | Bleeding outcome effect |
|---|---|---|---|---|
| Dabigatran | ||||
| Van Ryn et al. [16] | aPCC | Rat | aPTT unchanged | Decreased bleeding time |
| rfVIIa | Rat | aPTT decreased | Decreased bleeding time | |
| Van Ryn et al. [14] | 4-Factor PCC | Rat | PT decreased, aPTT unchanged | Decreased bleeding time |
| aPCC | Rat | PT decreased, aPTT unchanged, increased thrombin generation | Decreased bleeding time | |
| rfVIIa | PT and aPTT decreased | Decreased bleeding time | ||
| Lambourne et al. [38] | 4-Factor PCC | Mouse | No effect | No effect |
| rfVIIa | Mouse | aPTT decreased | No effect | |
| 4-Factor PCC + rfVIIa | Mouse | TT and aPTT decreased | No effect | |
| aPCC | Mouse | No effect | No effect | |
| Pragst et al. [39] | 4-Factor PCC | Rabbit | PT decreased, aPTT unchanged | Normalized blood loss |
| Zhou et al. [40] | 4-Factor PCC | Mouse ICH | Prevented hematoma expansion; control level mortality | |
| rfVIIa | Mouse ICH | Ineffective control of hematoma expansion | ||
| Marlu et al. [13] | 4-Factor PCC | Human in vitro | Increased amount of thrombin generation | |
| rfVIIa | Human in vitro | Corrected time to thrombin generation | ||
| aPCC | Human in vitro | Corrected time to thrombin generation | ||
| Eerenberg et al. [15] | 4-Factor PCC | Human | No effect on aPTT, TT, or ECT | |
| Khoo et al. [41] | aPCC | Human in vitro | Increased thrombin generation and corrected time to thrombin generation | |
| Warkentin et al. [17] | rfVIIa | Human case report | Decreased aPTT and PT | Decreased blood loss |
| Garber et al. [18] | rfVIIa | Human case report | Worsening ICH | |
| Truumees et al. [19] | rfVIIa | Human case report | Continued blood loss | |
| Lillo-Le Louët et al. [20] | 4-Factor PCC + rfVIIa | Human case report | PT and aPTT unchanged | Continued bleeding |
| 4-Factor PCC + rfVIIa | Human case report | PT and aPTT unchanged | Bleeding stopped with dialysis | |
| Wychowski and Kouides [42] | 3-Factor PCC | Human case report | TT and aPTT unchanged, PT decreased | No further bleeding |
| Dumkow et al. [43] | 3-Factor PCC | Human case report | Clinical bleeding and hemoglobin stabilized | |
| Rivaroxaban | ||||
| Perzborn and Tinel [44] | 4-factor PCC | Rat | PT decreased | Bleeding time decreased |
| Godier et al. [45] | 4-factor PCC | Rabbit | aPTT normalized, PT decreased | No effect on blood loss |
| rfVIIa | Rabbit | aPTT normalized, PT decreased | Decreased bleeding time, no effect on blood loss | |
| Perzborn et al. [46] | 4-Factor PCC | Rat | Decreased PT, normalized TAT concentration | Reduced bleeding time |
| aPCC | Rat | Decreased PT | Reduced bleeding time | |
| Primate | Reduced PT | Normalized bleeding time | ||
| rVIIa | Rat | Decreased PT | Reduced bleeding time | |
| Primate | Decreased PT | Bleeding time unchanged | ||
| Marlu et al. [13] | 4-Factor PCC | Human in vitro | Increased amount of thrombin generation | |
| rfVIIa | Human in vitro | Corrected time to thrombin generation | ||
| aPCC | Human in vitro | Corrected all thrombin generation parameters | ||
| Eerenberg et al. [15] | 4-Factor PCC | Human in vivo | Normalized PT and thrombin generation | |
| Dinkelaar et al. [47] | 4-Factor PCC | Human in vitro | No effect on PT or time to thrombin generation Normalized amount of thrombin generation | |
| Körber et al. [48] | 4-Factor PCC | Human in vitro | No effect on aPTT, PT | |
| rfVIIa | Human in vitro | Decreased clotting time, no effect on aPTT, PT | ||
| Apixaban | ||||
| Escolar et al. [23] | PCC | Human in vitro | Increased thrombin generation | |
| rfVIIa | Human in vitro | Increased thrombin generation | ||
| aPCC | Human in vitro | Increased thrombin generation |
aPCC: activated prothrombin complex concentrate; rfVIIa: recombinant factor VIIa.