(rivaroxaban)
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XARELTO® (rivaroxaban)
Medical Information
XARELTO - Reversal Agents in Human Studies - Andexanet alfaa (PRT064445) - Comparative Analysis of Andexanet alfa and PCC
Last updated : 05/16/2024
Rayatdoost et al (2024) conducted a study that compared the effectiveness of andexanet alfa (specific therapy) vs PCC (nonspecific therapy, including 4-factor PCCs [Cofact®, Beriplex®, Octaplex®, and Prothromplex] and aPCC [FEIBA]) in XARELTO-anticoagulated blood from 10 healthy donors.1
The mean age and weight of the subjects were 35 years and 75 kg, respectively. The blood cell counts were within normal adult ranges and the XARELTO plasma concentration was comparable in all spiked samples of each study group (the 6 DOAC reversal agents).1
Coagulation Measurements
PT
- 4-factor PCC concentrations equivalent to 25 and 50 IU kg-1 shortened the PT for all XARELTO concentrations (37.5, 75, 150, and 300 ng mL-1). However, 4-factor PCC only normalized PT when XARELTO concentration was <37.5 ng mL-1.1
- aPCC (at concentrations equivalent to 25 and 50 IU kg-1) reversed PT prolongation by 40-45% (P<0.0001 for both concentrations), and at a concentration equivalent to 50 IU kg-1 (~0.7 IU mL-1), aPCC reduced PT from 30 seconds to a minimum of 13.5 seconds for XARELTO concentration of 300 ng mL-1 (P<0.0001).1
- Andexanet alfa (~4.0 µM), reduced PT prolongation by 13-56% for all XARELTO concentrations (P<0.0001).1
aPTT
- 4-factor PCCs did not significantly affect aPTT for any XARELTO concentrations, whereas aPCC reduced aPTT prolongation by 20-30% for all XARELTO concentrations (P<0.0001).1
- Andexanet alfa reversed aPTT prolongation by 6-27% for all XARELTO concentrations. Additionally, at XARELTO concentration of 300 ng mL-1, the reversal effect was comparable for andexanet alfa (P=0.9996) and aPCC (P=0.8833; at a concentration equivalent to 50 IU kg-1).1
Thrombin Generation
- At lower XARELTO concentrations, 4-factor PCCs (both concentrations) partially reversed the anticoagulant effects, whereas that was not the case at higher XARELTO concentrations.1
- At XARELTO concentrations of >75 ng mL-1, a shortened lag time was observed for andexanet alfa and aPCC vs 4-factor PCCs (P<0.0001). At XARELTO concentrations of >150 ng mL-1, significant effects on increasing ETP were observed for andexanet alfa vs 4-factor PCCs and aPCC (P<0.05).1
Flow chamber experiments showed that 4-factor PCCs concentration-dependently increased thrombus formation. At a concentration equivalent to 50 IU kg-1, 4F-PCCs completed clot formation in 6 minutes.1
aAndexxa® (coagulation factor Xa [recombinant], inactivated-zhzo) is a product of AstraZeneca. Please refer to the Andexxa Prescribing Information for complete product information or call AstraZeneca at 1-800-236-9933.
aPCC, activated prothrombin complex concentrate; aPTT, activated partial thromboplastin time; DOAC, direct oral anticoagulants; ETP, endogenous thrombin potential; IU, international unit; PCC, prothrombin complex concentrate; PT, prothrombin time.
Reference
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1. Rayatdoost F, Deventer K, Rossaint R, et al. Comparative analysis of andexanet alfa and prothrombin complex concentrate in reversing anticoagulation by rivaroxaban ex vivo. Br J Anaesth. 2024;132(2):251-259.
