1. Prevention of exanguination under apixaban
Prevention of exanguination under apixaban
anticoagulation using Andexanet Alpha
in a polytrauma model
Oliver Grottke, Till Braunschweig, Rolf Rossaint, Pamela B Conley,
Janet M Leeds, Necib Akman, Markus Honickel
Department of Anaesthesiology
- Experimental Haemostaseology -
RWTH University Hospital Aachen, Germany

2. Summary: Andexanet alfa
Andexanet acts as a FXa decoy and retains high affinity for direct and indirect FXa inhibitors
It binds FXa inhibitors and counteracts their activity but is no longer capable of assembly into the prothrombinase complex
Andexanet
Native FXa
FXa Inhibitor
High affinity retained
GLA domain removed to prevent anticoagulant effect
Binding site
A419
S419
GLA
Catalytic Domain
Activity eliminated to prevent thrombin generation S S
N terminal residues retained to reduce immunogenicity
Lu G et al. Nat Med 2013;19(4):446-51

3. Experimental design – preclinical pig study
Apixaban oral pre-treatment: 3 days, 20 mg
1st group (no anticoagulation = sham), n=7
2nd group: control, n=7
3rd group: Andexanet alfa, 1000 mg/, n=7 Bolus i.v.
Surgical preparation
N=28, male pigs
Intubation
4th group: Andexanet alfa, 1000 mg/, n=7 Bolus plus 2 hour infusion (1200 mg: 2 x 600 mg) i.v.
Blood loss
Blood loss
Haemorrhagic shock 12 20 30 60 90
120
180
300
Time [min]
Trauma
Blood withdrawal for laboratory analysis
Volume replacement: Ringer’s
4 mL/kg/h
Bolus 25 mL/kg
(~1 L)
40 mL/kg/h
30 mL/kg/h
i.v., intravenous; p.o., per os

4. Andexanet alfa significantly reduced blood loss
*P<0.05 control vs. all, ‡P<0.05 sham vs. all

5. Thrombus structure: Electron microscopy
Control
Andexanet alfa
Magnification: 2500x
Magnification: 2500x

6. Plasma concentration of apixaban
*P<0.05 control vs. all