University of Hertfordshire

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Original languageEnglish
JournalJournal of the American College of Cardiology
Publication statusAccepted/In press - 26 May 2022

Abstract

Objective
To provide mechanistic insight into the determinants of endogenous fibrinolysis.
Background
Endogenous fibrinolysis is an important defence against arterial thrombosis. Earlier, we showed that hypofibrinolysis is risk factor for adverse cardiovascular events in acute coronary syndrome (ACS) patients (hazard ratio 9.1). 
Methods
In the prospective RISK-PPCI study, blood samples from 496 patients with ST-elevation myocardial infarction, taken at presentation, were assessed for whole blood endogenous lysis time (LT) and shear-induced thrombotic occlusion time (OT). In a subgroup of 129 patients, we additionally measured plasma clot lysis time (CLT), thrombin generation (TG), fibrinogen and high sensitivity C-reactive protein (hs-CRP).

Results
Whole blood lysis time correlated with fibrinogen (r=0.300, p=0.001), plasma CLT (r=0.195, p=0.032), hs-CRP (r=0.236, p=0.011) and inversely with OT (r = -0.200, p=0.026). TG was not directly related to LT, but more rapid TG was associated with faster OT (r = -0.263, p=0.012). Fibrinogen level correlated with fibrin clot density (r=0.545, p<0.001), hs-CRP (r=0.361, p<0.001) and plasma CLT (r=0.194, p=0.041). Hs-CRP correlated with fibrinogen, plasma CLT (r=0.269, p=0.005) and fibrin clot density (r=0.367, p<0.001).

Conclusion
The effectiveness of fibrinolysis in whole blood is related to fibrinogen, hs-CRP levels and shear-induced platelet reactivity, the latter related to thrombin generation. Further, plasma clot lysis in response to tissue-plasminogen activator is only weakly related to endogenous fibrinolysis in whole blood, indicating an important role for cellular components. Our data, strengthening the evidence for bi-directional cross talk between coagulatory and inflammatory pathways, provide mechanistic insights that could help guide pharmacological strategies to treat hypofibrinolysis.

ID: 27447721