Practice Guidelines for Reversal of New and Old Anticoagulants

Hartman, Sarah K.; Teruya, Jun

doi:10.1016/j.disamonth.2012.04.003

Cited by 9 publications

(7 citation statements)

References 54 publications

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“…To assess whether FXIa inhibition by SPGG2 can be reversed, we studied protamine, polybrene and SOS. Protamine is a clinically used arginine-rich polypeptide that counteracts the anticoagulant activity of UFH and LMWHs [29], whereas polybrene is a quaternary amine-containing hydrophobic polymer, which has been explored as a probe of electrostatic interactions [30]. SOS is an FDA approved antacid that is known to bind in heparin-binding sites on proteins such as thrombin [31].…”

Section: Resultsmentioning

confidence: 99%

Allosteric inhibition of factor XIa. Sulfated non-saccharide glycosaminoglycan mimetics as promising anticoagulants

Al‐Horani¹,

Gailani²,

Desai³

2015

Thrombosis Research

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Recent development of sulfated non-saccharide glycosaminoglycan mimetics, especially sulfated pentagalloyl glucopyranoside (SPGG), as potent inhibitors of factor XIa (FXIa) (J. Med. Chem. 2013; 56:867–878 and J. Med. Chem. 2014; 57:4805–4818) has led to a strong possibility of developing a new line of factor XIa-based anticoagulants. In fact, SPGG represents the first synthetic, small molecule inhibitor that appears to bind in site remote from the active site. Considering that allosteric inhibition of FXIa is a new mechanism for developing a distinct line of anticoagulants, we have studied SPGG’s interaction with FXIa with a goal of evaluating its pre-clinical relevance. Comparative inhibition studies with several glycosaminoglycans revealed the importance of SPGG’s non-saccharide backbone. SPGG did not affect the activity of plasma kallikrein, activated protein C and factor XIIIa suggesting that SPGG-based anticoagulation is unlikely to affect other pathways connected with coagulation factors. SPGG’s effect on APTT of citrated human plasma was also not dependent on antithrombin or heparin cofactor II. Interestingly, SPGG’s anticoagulant potential was diminished by serum albumin as well as factor XI, while it could be reversed by protamine or polybrene, which implies possible avenues for developing antidote strategy. Studies with FXIa mutants indicated that SPGG engages Lys529, Arg530 and Arg532, but not Arg250, Lys252, Lys253 and Lys255. Finally, SPGG competes with unfractionated heparin, but not with polyphosphates and/or glycoprotein Ibα, for binding to FXIa. These studies enhance understanding on the first allosteric inhibitor of FXIa and highlight its value as a promising anticoagulant.

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Section: Resultsmentioning

confidence: 99%

Allosteric inhibition of factor XIa. Sulfated non-saccharide glycosaminoglycan mimetics as promising anticoagulants

Al‐Horani¹,

Gailani²,

Desai³

2015

Thrombosis Research

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“…Indications for the use of these medications are similar to those of other anticoagulants. While there are no specific antidotes to these medications, there have been recent reports of the use of PCC to reverse the effect of these medications (Hartman and Teruya 2012).…”

Section: Other Coagulation Cascade Inhibitorsmentioning

confidence: 99%

Neurological Sports Medicine

2015

Encyclopedia of Trauma Care

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“…Dabigatran etexilate is an oral direct competitive reversible thrombin inhibitor approved in 2010. No effective reversal agent has been identified at this time (Hartman and Teruya 2012). Some management strategies have been suggested but with a paucity of evidence to support them.…”

Section: Direct Thrombin Inhibitorsmentioning

confidence: 99%