Titanium is a potent inducer of contact activation: implications for intravascular devices.
contact activation
factor XI
factor XII
prekallikrein
titanium
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
26
09
2022
revised:
07
12
2022
accepted:
15
12
2022
pmc-release:
01
05
2024
medline:
2
5
2023
pubmed:
26
1
2023
entrez:
25
1
2023
Statut:
ppublish
Résumé
Titanium (Ti) and its alloys are widely used in manufacturing medical devices because of their strength and resistance to corrosion. Although Ti compounds are considered compatible with blood, they appear to support plasma contact activation and may be thrombogenic. The objective of this study was to compare Ti and titanium nitride (TiN) with known activators of contact activation (kaolin and silica) in plasma-clotting assays and to assess binding and activation of factor XII, (FXII), factor XI (FXI), prekallikrein, and high-molecular-weight kininogen (HK) with Ti/TiN. Ti-based nanospheres and foils were compared with kaolin, silica, and aluminum in plasma-clotting assays. Binding and activation of FXII, prekallikrein, HK, and FXI to surfaces was assessed with western blots and chromogenic assays. Using equivalent surface amounts, Ti and TiN were comparable with kaolin and superior to silica, for inducing coagulation and FXII autoactivation. Similar to many inducers of contact activation, Ti and TiN are negatively charged; however, their effects on FXII are not neutralized by the polycation polybrene. Antibodies to FXII, prekallikrein, or FXI or coating Ti with poly-L-arginine blocked Ti-induced coagulation. An antibody to FXII reduced FXII and PK binding to Ti, kallikrein generation, and HK cleavage. Titanium compounds induce contact activation with a potency comparable with that of kaolin. Binding of FXII with Ti shares some features with FXII binding to soluble polyanions but may have unique features. Inhibitors targeting FXII or FXI may be useful in mitigating Ti-induced contact activation in patients with titanium-based implants that are exposed to blood.
Sections du résumé
BACKGROUND
Titanium (Ti) and its alloys are widely used in manufacturing medical devices because of their strength and resistance to corrosion. Although Ti compounds are considered compatible with blood, they appear to support plasma contact activation and may be thrombogenic.
OBJECTIVES
The objective of this study was to compare Ti and titanium nitride (TiN) with known activators of contact activation (kaolin and silica) in plasma-clotting assays and to assess binding and activation of factor XII, (FXII), factor XI (FXI), prekallikrein, and high-molecular-weight kininogen (HK) with Ti/TiN.
METHODS
Ti-based nanospheres and foils were compared with kaolin, silica, and aluminum in plasma-clotting assays. Binding and activation of FXII, prekallikrein, HK, and FXI to surfaces was assessed with western blots and chromogenic assays.
RESULTS
Using equivalent surface amounts, Ti and TiN were comparable with kaolin and superior to silica, for inducing coagulation and FXII autoactivation. Similar to many inducers of contact activation, Ti and TiN are negatively charged; however, their effects on FXII are not neutralized by the polycation polybrene. Antibodies to FXII, prekallikrein, or FXI or coating Ti with poly-L-arginine blocked Ti-induced coagulation. An antibody to FXII reduced FXII and PK binding to Ti, kallikrein generation, and HK cleavage.
CONCLUSION
Titanium compounds induce contact activation with a potency comparable with that of kaolin. Binding of FXII with Ti shares some features with FXII binding to soluble polyanions but may have unique features. Inhibitors targeting FXII or FXI may be useful in mitigating Ti-induced contact activation in patients with titanium-based implants that are exposed to blood.
Identifiants
pubmed: 36696212
pii: S1538-7836(22)18253-X
doi: 10.1016/j.jtha.2022.12.014
pmc: PMC10621279
mid: NIHMS1938470
pii:
doi:
Substances chimiques
Factor XI
9013-55-2
Factor XII
9001-30-3
Kaolin
24H4NWX5CO
Prekallikrein
9055-02-1
Titanium
D1JT611TNE
titanium nitride
6RW464FEFF
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1200-1213Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL101972
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL144113
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL140025
Pays : United States
Organisme : NHLBI NIH HHS
ID : R44 HL126235
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest statement D.G. is a consultant for pharmaceutical companies (Anthos Therapeutics; Aronora, Inc.; Bayer Pharma; Bristol-Myers Squibb; Ionis Pharmaceuticals; Janssen, Pharmaceuticals) with interests in targeting factor XI, factor XII, and prekallikrein for therapeutic purposes. M.W. and E.I.T are employees of Aronora, and they, as well as Oregon Health and Sciences University, may have financial interest in the results of this study. EPF is an employee of KalVista Pharmaceuticals Inc. The other authors have no conflicts to report.
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