Catalytic life of activated factor XIII in thrombi: Implications for fibrinolytic resistance and thrombus aging

Brian R. Robinson, Aiilyan K. Houng, Guy L. Reed

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Background - Because the increased fibrinolytic resistance of older thrombi may be caused by the continuous cross-linking action of fibrin-bound activated factor XIII (FXIIIa), we examined the persistence of FXIIIa catalytic activity in clots of various ages. Methods and Results - The time-related changes in FXIIIa activity in clots was measured with (1) α2-antiplasmin (α2AP), a physiological glutamine substrate; (2) α2AP13-24, a peptide; and (3) pentylamine, a nonspecific lysine substrate. The cross-linking of α2AP, α2AP13-24, and pentylamine into fibrin by clot-bound FXIIIa declined rapidly with half-lives of 19, 21, and 26 minutes, respectively. Mutational studies showed that glutamine 14 (but not glutamine 3 or 16) and valine 17 of α2AP13-24 were required for efficient cross-linking to fibrin. The loss of activity was not due primarily to FXIIIa proteolysis and was partially restored by reducing agents, suggesting that oxidation contributes to the loss of the enzyme's activity in clots. In vivo, the ability of thrombus-bound FXIIIa to cross-link an infused α2AP13-24 peptide into existing pulmonary emboli also declined significantly over time. Conclusions - FXIIIa cross-links α2AP and an α2AP peptide, in a sequence-specific manner, into formed clots with a catalytic half-life of ≃20 minutes. This indicates that FXIIIa activity is a hallmark of new thrombi and that the antifibrinolytic cross-linking effects of FXIIIa are achieved more rapidly in thrombi than previously believed.

Original languageEnglish (US)
Pages (from-to)1151-1157
Number of pages7
JournalCirculation
Volume102
Issue number10
DOIs
StatePublished - Sep 5 2000
Externally publishedYes

Keywords

  • Embolism
  • Fibrinolysis
  • Thrombus

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint

Dive into the research topics of 'Catalytic life of activated factor XIII in thrombi: Implications for fibrinolytic resistance and thrombus aging'. Together they form a unique fingerprint.

Cite this