PMID- 31914798
OWN - NLM
STAT- MEDLINE
DCOM- 20200720
LR  - 20200720
IS  - 1938-2723 (Electronic)
IS  - 1076-0296 (Print)
IS  - 1076-0296 (Linking)
VI  - 26
DP  - 2020 Jan-Dec
TI  - Assay-Based Differentiation in the Neutralization Profile of Unfractionated 
      Heparin, Enoxaparin, and Fondaparinux by Andexanet Alfa.
PG  - 1076029619895120
LID - 10.1177/1076029619895120 [doi]
LID - 1076029619895120
AB  - Andexanet alfa is a recombinant factor Xa decoy protein, designed to reverse 
      bleeding associated with oral anti-Xa agents. Andexanet alfa is also reported to 
      neutralize the effects of heparin-related drugs. This study focused on the 
      neutralization profiles of unfractionated heparin (UFH), enoxaparin, and, a 
      chemically synthetic pentasaccharide, fondaparinux by andexanet alfa. Whole blood 
      clotting studies were carried out using thromboelastography (TEG) and activated 
      clotting time (ACT). The anticoagulant profile of UFH, enoxaparin, and 
      fondaparinux was studied using the activated partial thromboplastin time (aPTT), 
      thrombin time (TT), and amidolytic anti-Xa, and anti-IIa methods. Thrombin 
      generation inhibition was studied using the calibrated automated thrombogram 
      system. Reversal of each of these agents was studied by supplementing andexanet 
      alfa at 100 microg/mL. In the TEG, andexanet alfa produced almost a complete reversal 
      of the anticoagulant effects of UFH and enoxaparin; however, it augmented the 
      effects of fondaparinux. In the ACT, aPTT, and TT, UFH produced strong 
      anticoagulant effects that were almost completely neutralized by andexanet alfa. 
      Enoxaparin produced milder anticoagulant responses that were partially 
      neutralized, whereas fondaparinux did not produce any sizeable effects. In the 
      anti-Xa and anti-IIa assays, UFH exhibited partial neutralization whereas 
      enoxaparin and fondaparinux did not show any neutralization. All agents produced 
      varying degrees of the inhibition of thrombin generation, which were 
      differentially neutralized by andexanet alfa. These results indicate that 
      andexanet alfa is capable of differentially neutralizing anticoagulant and 
      antiprotease effects of UFH and enoxaparin in an assay-dependent manner. However, 
      andexanet alfa is incapable of neutralizing the anti-Xa effects of fondaparinux.
FAU - Siddiqui, Fakiha
AU  - Siddiqui F
AUID- ORCID: 0000-0002-2219-7049
AD  - Cardiovascular Research Institute, Loyola University Chicago, Health Sciences 
      Division, Maywood, IL, USA.
FAU - Tafur, Alfonso
AU  - Tafur A
AD  - Northshore Cardiovascular Institute, NorthShore University Health Systems, 
      Skokie, IL, USA.
FAU - Bontekoe, Emily
AU  - Bontekoe E
AD  - Cardiovascular Research Institute, Loyola University Chicago, Health Sciences 
      Division, Maywood, IL, USA.
FAU - Iqbal, Omer
AU  - Iqbal O
AD  - Cardiovascular Research Institute, Loyola University Chicago, Health Sciences 
      Division, Maywood, IL, USA.
FAU - Jeske, Walter
AU  - Jeske W
AD  - Cardiovascular Research Institute, Loyola University Chicago, Health Sciences 
      Division, Maywood, IL, USA.
FAU - Mehrotra, Siddharth
AU  - Mehrotra S
AD  - Cardiovascular Research Institute, Loyola University Chicago, Health Sciences 
      Division, Maywood, IL, USA.
FAU - Hoppensteadt, Debra
AU  - Hoppensteadt D
AUID- ORCID: 0000-0001-8235-3624
AD  - Cardiovascular Research Institute, Loyola University Chicago, Health Sciences 
      Division, Maywood, IL, USA.
FAU - Ramacciotti, Eduardo
AU  - Ramacciotti E
AUID- ORCID: 0000-0002-5735-1333
AD  - Vascular and Endovascular Surgery, Santa Casa School of Medicine, Sao Paulo, SP, 
      Brazil.
FAU - Fareed, Jawed
AU  - Fareed J
AUID- ORCID: 0000-0003-3465-2499
AD  - Cardiovascular Research Institute, Loyola University Chicago, Health Sciences 
      Division, Maywood, IL, USA.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Clin Appl Thromb Hemost
JT  - Clinical and applied thrombosis/hemostasis : official journal of the 
      International Academy of Clinical and Applied Thrombosis/Hemostasis
JID - 9508125
RN  - 0 (Anticoagulants)
RN  - 0 (Enoxaparin)
RN  - 0 (Heparin Antagonists)
RN  - 0 (PRT064445)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.4.21.6 (Factor Xa)
RN  - J177FOW5JL (Fondaparinux)
SB  - IM
MH  - Anticoagulants/pharmacology
MH  - Blood Coagulation/drug effects
MH  - Blood Coagulation Tests
MH  - Drug Interactions
MH  - Enoxaparin/antagonists & inhibitors
MH  - Factor Xa/*pharmacology
MH  - Fondaparinux/antagonists & inhibitors
MH  - Heparin Antagonists/*pharmacology
MH  - Humans
MH  - Recombinant Proteins/*pharmacology
MH  - Thrombelastography
PMC - PMC7098205
OTO - NOTNLM
OT  - andexanet alfa
OT  - anticoagulants
OT  - enoxaparin
OT  - fondaparinux
OT  - pentasaccharide
OT  - unfractionated heparin
COIS- Declaration of Conflicting Interests: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2020/01/10 06:00
MHDA- 2020/07/21 06:00
PMCR- 2020/01/09
CRDT- 2020/01/10 06:00
PHST- 2020/01/10 06:00 [entrez]
PHST- 2020/01/10 06:00 [pubmed]
PHST- 2020/07/21 06:00 [medline]
PHST- 2020/01/09 00:00 [pmc-release]
AID - 10.1177_1076029619895120 [pii]
AID - 10.1177/1076029619895120 [doi]
PST - ppublish
SO  - Clin Appl Thromb Hemost. 2020 Jan-Dec;26:1076029619895120. doi: 
      10.1177/1076029619895120.