A functional assay for measuring activated thrombin-activatable fibrinolysis inhibitor in plasma
- PMID: 15203340
- DOI: 10.1016/j.ab.2004.04.007
A functional assay for measuring activated thrombin-activatable fibrinolysis inhibitor in plasma
Abstract
Thrombin-activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase found in plasma that is activated by thrombin, the thrombin-thrombomodulin complex, or plasmin. The active carboxypeptidase, TAFIa, attenuates fibrinolysis by removing newly exposed carboxy-terminal lysine residues on fibrin. The half-maximal effect of TAFIa on clot lysis occurs at 1 nM and the maximal effect occurs at 20 nM. Since the circulating concentration of the procarboxypeptidase is approximately 75 nM, only a small portion needs to be activated to have a significant effect on clot lysis. Several assays to measure total plasma TAFI levels and plasma TAFIa levels after it is fully activated exist. However, no currently available assay is sufficiently sensitive and specific to measure endogenous TAFIa in plasma. We have devised a new sensitive and specific assay for TAFIa in plasma that is based on physiologic function. This assay is based on the fact that TAFIa decreases the cofactor activity of high-molecular-weight fibrin degradation products in the stimulation of plasminogen cleavage in a concentration-dependent fashion. With this assay, we can measure TAFIa concentrations as low as 10 pM in plasma and it is not affected by variability in other hemostatic factors. This assay is reliable and repeatable with intra- and interassay variabilities of 6.5 and 6.1%, respectively.
Similar articles
-
An assay for measuring functional activated thrombin-activatable fibrinolysis inhibitor in plasma.Anal Biochem. 2008 Jan 1;372(1):32-40. doi: 10.1016/j.ab.2007.09.034. Epub 2007 Sep 29. Anal Biochem. 2008. PMID: 17967438
-
Thrombin activatable fibrinolysis inhibitor (TAFI): a role in pre-eclampsia?Clin Chim Acta. 2007 Mar;378(1-2):1-6. doi: 10.1016/j.cca.2006.10.014. Epub 2006 Oct 26. Clin Chim Acta. 2007. PMID: 17184758 Review.
-
Thrombin activatable fibrinolysis inhibitor (TAFI) does not inhibit in vitro thrombolysis by pharmacological concentrations of t-PA.Thromb Haemost. 2001 Apr;85(4):661-6. Thromb Haemost. 2001. PMID: 11341502
-
Thrombin activatable fibrinolysis inhibitor (TAFI) affects fibrinolysis in a plasminogen activator concentration-dependent manner. Study of seven plasminogen activators in an internal clot lysis model.Thromb Haemost. 2004 Mar;91(3):473-9. doi: 10.1160/TH03-06-0377. Thromb Haemost. 2004. PMID: 14983222
-
[Thrombin activatable fibrinolysis inhibitor (TAFI) and its importance in the regulation of fibrinolysis].Vnitr Lek. 2004 Jan;50(1):36-44. Vnitr Lek. 2004. PMID: 15015228 Review. Slovak.
Cited by
-
Thrombin activatable fibrinolysis inhibitor activation and bleeding in haemophilia A.Haemophilia. 2012 May;18(3):e316-22. doi: 10.1111/j.1365-2516.2011.02648.x. Epub 2011 Sep 20. Haemophilia. 2012. PMID: 21933309 Free PMC article.
-
Measuring fibrinolysis: from research to routine diagnostic assays.J Thromb Haemost. 2018 Apr;16(4):652-662. doi: 10.1111/jth.13957. Epub 2018 Feb 17. J Thromb Haemost. 2018. PMID: 29363269 Free PMC article. Review.
-
Kinetics of activated thrombin-activatable fibrinolysis inhibitor (TAFIa)-catalyzed cleavage of C-terminal lysine residues of fibrin degradation products and removal of plasminogen-binding sites.J Biol Chem. 2011 Jun 3;286(22):19280-6. doi: 10.1074/jbc.M110.215061. Epub 2011 Apr 5. J Biol Chem. 2011. PMID: 21467042 Free PMC article.
-
Thrombin-activable fibrinolysis inhibitor zymogen does not play a significant role in the attenuation of fibrinolysis.J Biol Chem. 2008 Apr 4;283(14):8863-7. doi: 10.1074/jbc.M800127200. Epub 2008 Feb 5. J Biol Chem. 2008. PMID: 18252711 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources