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

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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	24 Aug 2022
DOIs	https://doi.org/10.1016/j.jacbts.2022.05.007
Publication status	Published - 14 Nov 2022

Keywords

fibrinolysis
myocardial infarction
platelet function
thrombosis

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

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© 2022 The Author(s). Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the Creative Commons Attribution-NonCommercial-NoDerivatives CC BY-NC-ND licence, https://creativecommons.org/licenses/by-nc-nd/4.0/
Final published version, 1.14 MBLicence: CC BY-NC-ND

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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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AU - Kanji, Rahim

AU - Gue, Ying X.

AU - Farag, Mohamed F.

AU - Spencer, Neil H.

AU - Mutch, Nicola J.

AU - Gorog, Diana A.

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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.

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

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