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

• Published in: JACC. Basic to translational science Vol. 7; no. 11; pp. 1069 - 1082
• Main Authors: Kanji, Rahim, Gue, Ying X., Farag, Mohamed F., Spencer, Neil H., Mutch, Nicola J., Gorog, Diana A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2022; Elsevier
• Subjects: fibrinolysis; myocardial infarction; Original Research - Clinical; platelet function; thrombosis; vWF; OT; myocardial infarction; LT; platelet function; fibrinolysis; ACS; thrombosis; MACE; PCI; STEMI; PAI; t-PA; PCI, percutaneous coronary intervention; MACE, major adverse cardiovascular events; OT, occlusion time; STEMI, ST-segment elevation myocardial infarction; ACS, acute coronary syndrome; LT, lysis time; vWF, von Willebrand factor; PAI, plasminogen activator inhibitor; t-PA, tissue plasminogen activator
• ISSN: 2452-302X; 2452-302X
• DOI: 10.1016/j.jacbts.2022.05.007

[Display omitted] •Hypofibrinolysis is a recently-recognized risk factor for recurrent cardiovascular events in patients with STEMI, but its mechanistic determinants are not well understood.•In patients with STEMI, we show that the effectiveness of endogenous fibrinolysis in whole blood is related to fibrinogen, hs-CRP, and shear-induced platelet reactivity, the latter related to thrombin generation.•Endogenous fibrinolysis in whole blood is only weakly related to plasma clot lysis in response to t-PA, indicating an important role for cellular components in determining fibrinolytic status.•These findings strengthen the evidence for bidirectional crosstalk between coagulation and inflammation and provide mechanistic insights that could help guide pharmacological strategies to treat hypofibrinolysis, a potentially modifiable cardiovascular risk factor. 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.