|
Zhou et al., 2011 [54]
|
Murine intracerebral haemorrhage model
|
9.0
|
100
|
Haematoma volume:
|
PCC effectively prevented haematoma growth and significantly reduced 24-h mortality
|
|
Post-dabigatran: 17.0 ± 4.1 mm3
|
|
Post-PCC: 11.7 ± 3.0 mm3
|
|
Mortality:
|
|
Control animals: 30 %
|
|
PCC-treated mice: 4 %
|
|
Pragst et al., 2012 [55]
|
Leporine standardised kidney injury model
|
0.4
|
20, 35 or 50
|
Blood loss:
|
PCC resulted in a dose-dependent reduction in blood loss and acceleration in haemostasis. At the highest dose, blood loss was normalised in all animals. All doses of PCC successfully treated dabigatran-induced anticoagulation at plasma concentrations similar to those seen in patients receiving dabigatran
|
|
Control: 1.0–7.2 ml
|
|
Post-dabigatran: mean 29 ml
|
|
Post-PCC: decreased by 5.44 ml per 10 IU/kg PCC
|
|
No change in aPTT
|
|
PT shortened by 0.335 s per 10 IU/kg PCC
|
|
Herzog et al., 2014 [56]
|
Leporine arterial venous shunt model
|
0, 0.075, 0.2, 0.45
|
0, 5 or 300
|
Bleeding time:
|
Dabigatran-induced bleeding was effectively reversed by PCC. The thromboembolic risk associated with PCC administration appeared to be reduced due to the persistence of dabigatran in the plasma
|
|
Increasing PCC doses shortened time to haemostasis for rabbits treated with 0.2 mg/kg dabigatran
|
|
No dose of PCC could reverse the effects of 0.45 mg/kg dabigatran on time to haemostasis
|
|
Thrombosis:
|
|
The frequency of pulmonary thrombi decreased progressively with increasing concomitant dabigatran dose
|
|
Grottke et al., 2014 [49]
|
Porcine liver trauma model
|
30 (daily oral dose) then intravenous infusion to reach supratherapeutic plasma concentration
|
PCC:
|
PCC:
|
Both PCC and aPCC diminished the effects of dabigatran, restoring ROTEM® parameters and PT to 80–90 % of baseline
|
|
30 or 60
|
No effect on aPTT
|
|
aPCC:
|
aPCC:
|
|
30 or 60
|
No effect on aPTT
|
|
Honickel et al., 2015 [57]
|
Porcine polytrauma model
|
30 (daily oral dose) then intravenous infusion to reach supratherapeutic plasma concentration
|
aPCC:
|
50 IU/kg aPCC associated with significant reduction in blood loss vs placebo group and those treated with 25 IU/kg
|
aPCC (50 IU/kg) is effective in reducing blood loss in anticoagulated pigs
|
|
25 or 50
|
|
Lower-dose aPCC (25 IU/kg) had an initial effect that was not sustained, suggesting stoichiometric excess of prothrombin vs dabigatran may be required
|
|
Honickel et al., 2015 [18]
|
Porcine polytrauma model
|
30 (daily oral dose) then intravenous infusion to reach supratherapeutic plasma concentration
|
30 or 60
|
Significant decreases in PT, CT and CFT
|
Three-factor and four-factor PCCs are similarly effective for dabigatran reversal
|
|
Honickel et al., 2015 [58]
|
Porcine polytrauma model
|
30 (daily oral dose) then intravenous infusion to reach supratherapeutic plasma concentration
|
25, 50 or 100
|
50 and 100 IU/kg PCC associated with significant reductions in blood loss vs placebo group and those treated with 25 IU/kg
|
PCC can be effective in reducing blood loss in anticoagulated pigs
|
|
High doses may induce a procoagulant state
|
|
Low doses may be ineffective
|
|
High-dose PCC (100 IU/kg) led to overcorrection of thrombin generation
|
