Alteplase Reversal Information

Andexanet alfa is FDA indicated for reversal of apixaban, but is NOT currently on formulary at St. Vincent. It is recommended for life-threatening bleeding, bleeding into a critical organ. It is a modified human factor Xa decoy protein that binds and sequesters factor Xa inhibitors, but also TFPI. Anti FXa assay results rapidly decrease within 2 minutes after bolus and this is maintained throughout the duration of the continuous infusion. Anti Xa levels returned to placebo levels approximately 2 hours after completion of bolus or infusion. Andexanet alfa is associated with pro-thrombotic risks.

Recommended Adult dose:

Apixaban last dose	Timing of apixaban last dose before Andexxa initiation
	< 8 hrs or Unknown	< 8 hrs or Unknown
≤ 5 mg	Low dose: Initial IV Bolus 400 mg at a target rate of 30 mg/min; Follow-on IV Infusion: 4 mg/min for up to 120 minutes (480 mg)	Low dose: Initial IV Bolus 400 mg at a target rate of 30 mg/min; Follow-On IV Infusion: 4 mg/min for up to 120 minutes
> 5 mg or Unknown	High dose: Initial IV Bolus: 800 mg at a target rate of 30 mg/min; Follow-on IV Infusion: 8 mg/min for up to 120 minutes (960 mg)

Andexanet Alpha Pediatric dosing: NO published pediatric dosing is available. Recommend considering the following dosing in patients
< 40kg:
- Bolus: 20 mg/kg (max 800 mg)
- Infusion: 0.2 mg/kg/min for up to 120 minutes
Critical site bleeds: Intracranial hemorrhage, including intraparenchymal, subdural, epidural, and subarachnoid hemorrhages; Other CNS hemorrhage, including intraocular, intra- or extra-axial spinal hemorrhages; Pericardial tamponade; Airway, including posterior epistaxis; Hemothorax, intraabdominal bleeding, and retroperitoneal hemorrhage; Extremity bleeds, including intramuscular and intraarticular bleeding concerning for compartment syndrome, bleeding associated with hemodynamic instability, bleeding in a noncompressible vessel (e.g., subclavian)

Kcentra (prothrombin complex concentrate) 25-50 units/kg for severe bleeding or NovoSeven (rFVIIa) 90 mcg/kg. FEIBA (activated PCC) 50 units/kg would be a last resort due to higher thrombosis risk. They are on formulary at PMCH but are not labeled by the manufacturer for reversal of apixaban.
In the setting of overdose, also consider administration of activated charcoal (50 g) if within 2 hours of dose.
Apixaban is NOT dialyzable because it is mostly protein bound.
Repeat monitoring tests for anticoagulant and platelets, PT, PTT, and fibrinogen after infusing a reversal agent and q 4-6 hours until severe bleeding risk has passed. Determine if and when anticoagulation should be reinitiated and what agent. Monitor patient for thrombosis and bleeding.

Abbreviation	Definition
AAA	Abdominal Aortic Aneurysm
ABCs	Airway, breathing and circulation
ABS	Acrylonitrile Butadiene Styrene
ACS	Acute Coronary Syndrome
ACT	Activated clotting tim
Anti-Xa	Anti factor Xa level; used for monitoring heparins
APLA	Antiphospholipid antibody syndrome
approx	Approximately
APTT	Activated partial thromboplastin time
ASA	Acetylsalicylic acid
AT3	Antithrombin 3
BID	Twice Daily
CABG	Coronary artery bypass grafting
CBC	Complete blood count
CDT	Catheter-directed Thrombolysis
CI	Continuous infusion
CMP	Comprehensive metabolic panel
COX	Cyclooxygenase
Cryo	Cryoprecipitate
DAT	Direct antiglobulin test
DDAVP	Desmopressin acetate
DIC	Disseminated intravascular coagulation
DVT	Deep venous thrombosis
EACA	Epsilon aminocaproic acid
F	Factor
FEIBA	Factor eight inhibitor bypassing activity
FFP	Fresh frozen plasma
FIX	Factor IX
Gm	Gram
HAV	Hepatitis A virus
Hb	Hemoglobin
HBV	Hepatitis B virus
HCV	Hepatitis C virus
HD	Hemodialysis
HIV	Human immunodeficiency virus
hrs	Hours
I.V.	Intravenous
ICU	Intensive care unit
INR	International normalized ratio
IPA	Inhibition of Platelet Aggregation
IU/kg	International units per kilogram of body weight
LFT	Liver function tests
LMWH	Low molecular weight heparin mcg
mcg	Microgram
mg	Milligram
MI	Myocardial infarction
min	Minutes
NOAC	Non Vitamin K Oral Anticoagulant
P.O.	Per os (oral)
PAI-1	Plasminogen activator inhibitor-1
PCC	Prothrombin Complex Concentration
PCI	Percutaneous Coronary Intervention
PE	Pulmonary embolism
PFA-100	Platelet function analyzer-100; in vitro bleeding time
PRN	As Needed
PT	Prothrombin time
Q	Every
QID	Four times daily
RES	Reticuloendothelial system
rt-PA	Recombinant tissue plasminogen activator
rVIIa	Recombinant factor VIIa (NovoSeven RT)
SC	Subcutaneous
STEMI	ST-Elevation Myocardial Infarction
TCT	Thrombin clotting time
TEG	Thromboelastogram
TPA	Tissue plasminogen activator
U/kg	Units/ kg
UFH	Unfractionated heparin
VKA	Vitamin K antagonists

Abbreviations