Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Aug 24;7(11):1069-1082.
doi: 10.1016/j.jacbts.2022.05.007. eCollection 2022 Nov.

Determinants of Endogenous Fibrinolysis in Whole Blood Under High Shear in Patients With Myocardial Infarction

Rahim Kanji  1   2 , Ying X Gue  2   3 , Mohamed F Farag  2   3 , Neil H Spencer  4 , Nicola J Mutch  5 , Diana A Gorog  1   2   3
Affiliations

Determinants of Endogenous Fibrinolysis in Whole Blood Under High Shear in Patients With Myocardial Infarction

Rahim Kanji et al. JACC Basic Transl Sci. .

Abstract

Hypofibrinolysis is a recently-recognized risk factor for recurrent cardiovascular events in patients with ST-segment elevation myocardial infarction (STEMI), but the mechanistic determinants of this are not well understood. In patients with STEMI, we show that the effectiveness of endogenous fibrinolysis in whole blood is determined in part by fibrinogen level, high sensitivity C-reactive protein, and shear-induced platelet reactivity, the latter directly related to the speed of thrombin generation. Our findings strengthen the evidence for the role of cellular components and bidirectional crosstalk between coagulatory and inflammatory pathways as determinants of hypofibrinolysis.

Keywords: ACS, acute coronary syndrome; LT, lysis time; MACE, major adverse cardiovascular events; OT, occlusion time; PAI, plasminogen activator inhibitor; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction; fibrinolysis; myocardial infarction; platelet function; t-PA, tissue plasminogen activator; thrombosis; vWF, von Willebrand factor.

PubMed Disclaimer

Conflict of interest statement

This work was supported in part by a grant from Alpha MD, London, United Kingdom. Dr Mutch was supported by the British Heart Foundation PG/15/82/31721 and Friends of Anchor. Dr Gorog has received institutional research grants from Bayer, Medtronic, Alpha MD, and Boehringer Ingelheim; has received speaker’s fees from AstraZeneca and Boehringer Ingelheim; and is related through family to a company director in Thromboquest Ltd, but neither she, nor her spouse or children, have financial involvement or equity interest in and they have received no financial assistance, support, or grants from the aforementioned. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Relationship Between Whole Blood Endogenous Fibrinolysis and Plasma Clot Lysis and Turbidity Relationship between whole blood endogenous fibrinolysis (lysis time) and plasma clot lysis time (50% clot lysis) (A) and fold-increase in maximum clot absorbance as quantified by turbidity measurements (B).
Figure 2
Figure 2
Relationship Between Occlusion Time and Endogenous Fibrinolysis (Lysis Time) in Whole Blood There was no significant difference between OT quartiles (Kruskal-Wallis test; P = 0.154). There is a relationship at the extremes of LT (ie, Q1 and Q4, Mann-Whitney U test P = 0.030) which is biologically plausible and relevant. ∗P < 0.05.
Figure 3
Figure 3
Relationship Between Occlusion Time in Whole Blood and Lag Time to Thrombin Generation Individual pairwise comparisons were conducted, and after Bonferroni correction, no significant differences were detected.
Figure 4
Figure 4
Relationship Between Occlusion Time in Whole Blood and Velocity Index of Thrombin Generation Individual pairwise comparisons were conducted, and after Bonferroni correction, only the difference between Q1 and Q4 was significant. ∗P < 0.05.
Figure 5
Figure 5
Kaplan-Meier Curves Showing Event-Free Survival for Patients Based on Whole Blood Endogenous Fibrinolysis and Plasma Clot Lysis Kaplan-Meier curves showing event-free survival for patients based on (A) whole blood endogenous fibrinolysis (measured in 129 patients): lysis time <2,500 and ≥2,500 seconds (log rank P = 0.001; HR: 3.6 [95% CI: 1.5-8.5; P = 0.002]) and (B) 50% plasma clot lysis time (measured in 121 patients [in 8 patients, stored plasma was insufficient for analysis]) <78.5 and ≥78.5 minutes (log rank P = 0.037; HR: 4.1 [95% CI: 0.96-17.2; P = 0.057]).
See this image and copyright information in PMC

References

    1. Gorog D.A., Lip G.Y.H. Impaired spontaneous/endogenous fibrinolytic status as new cardiovascular risk factor? JACC review topic of the week. J Am Coll Cardiol. 2019;74(10):1366–1375. - PubMed
    1. Kietsiriroje N., Ariëns R., Ajjan R. Fibrinolysis in acute and chronic cardiovascular disease. Semin Thromb Hemost. 2021;47(5):490–505. - PubMed
    1. Okafor O.N., Gorog D.A. Endogenous fibrinolysis: an important mediator of thrombus formation and cardiovascular risk. J Am Coll Cardiol. 2015;65(16):1683–1699. - PubMed
    1. Krychtiuk K.A., Speidl W.S., Giannitsis E., et al. Biomarkers of coagulation and fibrinolysis in acute myocardial infarction: a joint position paper of the Association for Acute CardioVascular Care and the European Society of Cardiology Working Group on Thrombosis. Eur Hear J Acute Cardiovasc Care. 2021;10(3):343–355. - PubMed
    1. Farag M., Spinthakis N., Gue Y.X., et al. Impaired endogenous fibrinolysis in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention is a predictor of recurrent cardiovascular events: the RISK PPCI study. Eur Heart J. 2018;14(40):295–305. - PubMed