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

JACC Basic Transl Sci. 2022 Aug 24;7(11):1069-1082. doi: 10.1016/j.jacbts.2022.05.007. eCollection 2022 Nov.

Authors

Rahim Kanji^{1

2}, Ying X Gue^{2

3}, Mohamed F Farag^{2

3}, Neil H Spencer⁴, Nicola J Mutch⁵, Diana A Gorog^{1

2

3}

Affiliations

¹ Faculty of Medicine, National Heart and Lung Institute, Imperial College, London, United Kingdom.
² Cardiology Department, East and North Hertfordshire NHS Trust, Stevenage, Hertfordshire, United Kingdom.
³ School of Life and Medical Sciences, Postgraduate Medical School, University of Hertfordshire, Hatfield, Hertfordshire, United Kingdom.
⁴ Statistical Services and Consultancy Unit, Hertfordshire Business School, University of Hertfordshire, Hatfield, Hertfordshire, United Kingdom.
⁵ Aberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom.

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.