Can measuring endogenous fibrinolysis help in the risk stratification of future thrombotic events in patients with cardiovascular disease?
File(s)
Author(s)
Kanji, Rahim
Type
Thesis or dissertation
Abstract
Hypofibrinolysis is an important contributor and predictor of recurrent atherothrombotic events in patients with acute coronary syndrome (ACS). However, whether fibrinolysis efficiency is the aetiological factor for the higher risk of recurrent major adverse cardiovascular events (MACE) in patients with diabetes, and lower risk of MACE in patients achieving spontaneous reperfusion in ST-Elevation Myocardial Infarction (STEMI), is uncertain.
There is also uncertainty regarding the pathomechanism for the higher risk of stroke and subclinical valve thrombosis in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI).
I sought to assess whether the Global Thrombosis Test, exposing whole blood to high shear (thereby serving as a physiological model in vitro), and calculating the time for occlusive thrombus formation (OT), and thereafter the spontaneous reflow of blood (LT), a marker of fibrinolysis efficiency, could help determine pathomechanism.
I recruited patients with severe AS and consecutive patients with ACS to prospective observational studies, and obtained blood samples at specified time points to determine thrombotic profile.
Compared to patients without diabetes, patients with diabetes and ACS had significantly longer LT, reflecting hypofibrinolysis, which was an independent predictor of future MACE at 1 year.
In patients with STEMI, those with spontaneous reperfusion had lower platelet reactivity and more efficient endogenous fibrinolysis, compared to patients with an occluded infarct-related artery. This resulted in superior outcomes, including MACE, up to 4 years.
Determinants of endogenous fibrinolysis (in a sub-analysis), included shear-induced platelet reactivity, fibrinogen and CRP.
In patients with severe AS, a significant increase in LT was observed post-TAVI. This increase was greater in patients with stroke post-discharge. LT was also significantly elevated in patients with persistent subclinical valve thrombosis.
Variability in endogenous fibrinolysis efficiency explains the varying risk profile of certain patient groups. Identifying treatment targets to modulate fibrinolysis efficiency, is therefore warranted.
There is also uncertainty regarding the pathomechanism for the higher risk of stroke and subclinical valve thrombosis in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI).
I sought to assess whether the Global Thrombosis Test, exposing whole blood to high shear (thereby serving as a physiological model in vitro), and calculating the time for occlusive thrombus formation (OT), and thereafter the spontaneous reflow of blood (LT), a marker of fibrinolysis efficiency, could help determine pathomechanism.
I recruited patients with severe AS and consecutive patients with ACS to prospective observational studies, and obtained blood samples at specified time points to determine thrombotic profile.
Compared to patients without diabetes, patients with diabetes and ACS had significantly longer LT, reflecting hypofibrinolysis, which was an independent predictor of future MACE at 1 year.
In patients with STEMI, those with spontaneous reperfusion had lower platelet reactivity and more efficient endogenous fibrinolysis, compared to patients with an occluded infarct-related artery. This resulted in superior outcomes, including MACE, up to 4 years.
Determinants of endogenous fibrinolysis (in a sub-analysis), included shear-induced platelet reactivity, fibrinogen and CRP.
In patients with severe AS, a significant increase in LT was observed post-TAVI. This increase was greater in patients with stroke post-discharge. LT was also significantly elevated in patients with persistent subclinical valve thrombosis.
Variability in endogenous fibrinolysis efficiency explains the varying risk profile of certain patient groups. Identifying treatment targets to modulate fibrinolysis efficiency, is therefore warranted.
Version
Open Access
Date Issued
2023-10-25
Date Awarded
2024-07-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Gorog, Diana
Prasad, Sanjay
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)