Table 1.
Effects on coagulation parameters of experimental anticoagulation and anticoagulation reversal
| Animal, strain | Anticoagulant | Dose | Haemostatic agent | Coagulation test and effect relative to controls* | |
|---|---|---|---|---|---|
| Vitamin K antagonists: anticoagulation | |||||
|
| |||||
| Foerch et al (2008)31 | Mice, CD-1 | Warfarin | Dose 1: 2 mg/kg per 24 h; dose 2: 2 mg/ kg/24 h for 30 h | None | PT. Dose 1: 4·4-fold increase; dose 2: 9-fold increase |
| Illanes et al (2010)32 | Mice, C57BL/6 | Warfarin | 0·4 mg/kg/24 h for 72 h | None | PT. 6·6-fold increase |
| Lauer et al (2011)33 | Mice, CD-1 | Warfarin | 2 mg/kg/24 h for 30 h | None | PT. 4·9-fold increase |
|
| |||||
| Vitamin K antagonists: anticoagulation reversal | |||||
|
| |||||
| Foerch et al (2009)34 | Mice, CD-1 | Warfarin | 2 mg/kg per 24 h | PCC 100 U/kg | PT. 4·0-fold decrease |
| Illanes et al (2011)35 | Mice, C57BL/6 | Warfarin | 0·4 mg/kg/24 h for 72 h | FFP 200 μL; PCC 100 U/kg; rFVIIa 3·5 mg/kg; rFVIIa 10 mg/kg; and TA 400 mg/kg | PT. FFP: 2·6-fold decrease; PCC: 5·1-fold decrease; rFVIIa 3·5 mg/kg: 1·5-fold decrease; rFVIIa 10 mg/kg: 1·7-fold decrease; TA: 1·15-fold decrease |
| Schlunk et al (2012)36 | Mice, CD-1 | Warfarin | 2 mg/kg per 24 h | PCC 100 U/kg; rFVIIa 1 mg/kg | PT. PCC: 3·1-fold decrease; rFVIIa: 4·7-fold decrease |
|
| |||||
| New oral anticoagulants: anticoagulation | |||||
|
| |||||
| Lauer et al (2011)33 | Mice, CD-1 | Dabigatran | Dose 1: 37·5 mg/kg p.o.; dose 2: 75·0 mg/kg p.o.; dose 3: 112·5 mg/kg p.o. | None | aPTT and dTT. Dose 1: aPTT 2·6-fold increase, dTT 6·6-fold increase; dose 2: aPTT 3·1-fold increase, dTT 7·3-fold increase; dose 3: aPTT 4·8-fold increase; dTT: 9·2-fold increase |
| Zhou et al (2011)37 | Mice, C57BL/6 | Dabigatran | Dose 1: 2·25 mg/kg i.p.; dose 2: 4·5 mg/kg i.p.; dose 3: 9 mg/kg i.p. | None | ECT and TVBT. Dose 1: ECT n.d., TVBT 1·5-fold increase; dose 2: ECT ≥7·5-fold increase, TVBT 20-fold increase; dose 3: ECT ≥7·5-fold increase; TVBT ≥20-fold increase |
| Zhou et al (2013)38 | Mice, C57BL/6 | Rivaroxaban | Dose 1: 10 mg/kg p.o.; dose 2: 30 mg/kg p.o. | None | PT. Dose 1: 2·6-fold increase; dose 2:3·5-fold increase |
|
| |||||
| New oral anticoagulants: anticoagulation reversal | |||||
|
| |||||
| Zhou et al (2011)37 | Mice, C57BL/6 | Dabigatran | 9 mg/kg i.p. | Dose 1: PCC 25 U/kg; dose 2: PCC 50 U/kg; dose 3: PCC 100 U/kg | TVBT. Dose 1: no change; dose 2: no change; dose 3: decrease |
| Zhou et al (2013)38 | Mice, C57BL/6 | Rivaroxaban | 30 mg/kg p.o. | PCC 100 U/kg; rFVIIa 1 mg/kg; and FFP 200 μL per mouse | PT. PCC: no change; rFVIIa: decrease; FFP: no change |
PT=prothrombin time. PCC=prothrombin complex concentrate. FFP=fresh frozen plasma. rFVIIa=recombinant factor VIIa. TA=tranexamic acid. p.o.=per os. aPTT=activated partial thromboplastin time. dTT=diluted thrombin time. i.p.=intraperitoneal. ECT=ecarin clotting time. TVBT=tail vein bleeding time. n.d.=not determined.
*
Controls were either non-anticoagulated (sham-treated) animals or anticoagulated animals that received sham treatment for anticoagulation reversal.