Table 3.

Summary of ex vivo and in vivo evidence for reversal of factor Xa inhibitor anticoagulant effect

Reversal strategy	Animal studies (factor-Xa-inhibitor-treated animals)	Ex vivo studies (factor-Xa-inhibitor-treated healthy volunteers or patients)	Ex vivo studies (factor-Xa-inhibito- and reversal-agent-treated healthy volunteers)
Nonspecific reversal agents
PCC	Rivaroxaban Corrected aPTT [25] Variably corrected PT [25,26] No reduction of blood loss in rabbits [25] Reduced bleeding time in rats but not primates [26]	Rivaroxaban Corrected PT [16] Variably corrected TG indices [14,16] No correction of anti-Xa activity [16]	Rivaroxaban Corrected PT [13]
aPCC	Rivaroxaban Corrected aPTT [25] Variably corrected PT [25,26] No reduction of blood loss in rabbits [25] Reduced bleeding time in rats and primates [26] Edoxaban Reduced bleeding time in rats [24]	Rivaroxaban Corrected PT [16] Corrected TG indices [14,16] No correction of anti-Xa activity [16]
rVIIa	Rivaroxaban Corrected PT [26] Reduced bleeding time in rats but not primates [26] Edoxaban Reduced bleeding time in rats [24]	Rivaroxaban Corrected PT [16] Variably corrected TG indices [14] No correction anti-Xa activity [16]
Specific reversal agent
PRT064445 [11]	Rivaroxaban Corrected INR, PT, aPTT, anti-Xa activity Reduced blood loss Apixaban, betrixaban Corrected INR, PT, aPTT, anti-Xa activity		Apixaban Decreased anti-Xa activity

Abbreviations: aPTT, activated partial thromboplastin time; aPCC, activated prothrombin complex concentrate; INR, international normalized ratio; PCC, prothrombin complex concentrate; PT, prothrombin time; rVIIa, recombinant activated factor VII; TEM, thromboelastometry; TG, thrombin generation.