Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications

Table 2

Properties of specific reversal agents for use against the DOACs [21, 35–37, 39–41].

	Idarucizumab	Andexanet-α	Ciraparantag
Target	Dabigatran	Factor Xa inhibitors, LMWH, fondaparinux	Factor Xa inhibitors, LMWH, fondaparinux, heparin, and dabigatran
Compound	Humanized monoclonal antibody fragment	Modified recombinant derivative of human FXa (inactive)	Synthetic small molecule
Mechanism of action	350x higher affinity binding to dabigatran than dabigatran-thrombin-binding affinity	“Decoy” receptor for FXa inhibitor with higher binding affinity than natural FXa	Binds to target via noncovalent hydrogen bonds and charge-charge interactions preventing anticoagulants from binding to endogenous targets
Dose	5 g (as sequential i.v. boluses of 2.5 g each)	210–420 mg i.v. bolus + 2 h i.v. infusion at 4–8 mg/min	100–400 mg i.v. bolus
Onset of action	Immediate	Within 5 minutes	Within 10 minutes
Duration of reversal	12 hours	1-2 hours	24 hours
Elimination	Renal	Unknown	Unknown
Clinical trial	REVERSE-AD [35, 36]	ANNEXA-A [42] ANNEXA-R [42]	Ansell et al. [43]
Developmental phase	III/approved	III	II
Storage/stability	Refrigerated/2 years	Refrigerated/2 years	Room temperature/2 years
Side effects	Injection site skin reaction and hematoma, epistaxis	Urticarial, flushing, dysgeusia, headache	Flushing, dysgeusia, headache

FXa = factor Xa, g = grams, i.v. = intravenous, and mg = milligram.