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

Rahim Kanji; Ying X. Gue; Mohamed F. Farag; Neil H. Spencer; Nicola J. Mutch; Diana A. Gorog

doi:10.1016/j.jacbts.2022.05.007

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

Rahim Kanji
, Ying X. Gue
, Mohamed F. Farag
, Neil H. Spencer
, Nicola J. Mutch
, Diana A. Gorog^*

^*Corresponding author for this work

Imperial College London
East and North Hertfordshire NHS Trust
University of Hertfordshire

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

10 Downloads (Pure)

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.

Original language	English
Pages (from-to)	1069-1082
Number of pages	14
Journal	JACC: Basic to Translational Science
Volume	7
Issue number	11
Early online date	14 Nov 2022
DOIs	https://doi.org/10.1016/j.jacbts.2022.05.007
Publication status	Published - Nov 2022

Bibliographical note

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.

Funding

The authors would like to thank Mrs M. Donnarumma and Mrs L. Robertson for their strong technical support in performing plasma clot lysis and thrombin generation assays.

Keywords

fibrinolysis
Myocardial infarction
platelet function
thrombosis

Access to Document

10.1016/j.jacbts.2022.05.007Licence: CC BY-NC-ND

Kanji_etal_JACC_Determinants_of_Endogenous_VOR
https://creativecommons.org/licenses/by-nc-nd/4.0/
Final published version, 1.14 MBLicence: CC BY-NC-ND

Cite this

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title = "Determinants of Endogenous Fibrinolysis in Whole Blood Under High Shear in Patients With Myocardial Infarction",

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.",

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author = "Rahim Kanji and Gue, \{Ying X.\} and Farag, \{Mohamed F.\} and Spencer, \{Neil H.\} and Mutch, \{Nicola J.\} and Gorog, \{Diana A.\}",

note = "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{\textquoteright}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.",

year = "2022",

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AU - Spencer, Neil H.

AU - Mutch, Nicola J.

AU - Gorog, Diana A.

N1 - 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.

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N2 - 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.

AB - 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.

KW - fibrinolysis

KW - Myocardial infarction

KW - platelet function

KW - thrombosis

UR - https://www.scopus.com/pages/publications/85141777397

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JO - JACC: Basic to Translational Science

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ER -

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

Abstract

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Keywords

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