Figure - available from: Clinical and Applied Thrombosis/Hemostasis
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Schematic showing the principle of thrombus formation in the global thrombosis test. As blood flows through narrow gaps adjacent to the higher ball bearing, high shear forces in this zone cause shear-induced platelet aggregation. Downstream, in the area between the 2 ball bearings, at low shear, activated platelets begin to aggregate. These travel downstream to eventually occlude the narrow gaps adjacent to the smaller ball bearing, by occlusive thrombus.
Source publication
Thrombus formation in a severely stenosed artery is initiated by high shear activation of platelets, with soluble platelet agonists, such as ADP and thromboxane, playing only a secondary role in the growth and stability of the thrombus. Conventional platelet function tests, however, assess only the soluble agonist-dependent pathway of platelet aggr...
Citations
... This not only highlights the fact that a "global" assessment of thrombotic status is preferable but also that there is a need for a novel biomarker that can identify patients with STEMI with a low likelihood of spontaneous reperfusion. There are currently 2 methods to assess global endogenous fibrinolysis, namely viscoelastic tests such as the rotational thromboelastometry ROTEM® (Pentapharm GmbH, Munich, Germany) or thromboelastography (Haemonetics Ltd., Coventry, UK), which assesses thrombus formation and lysis at low shear rates, more akin to venous thrombosis, and the Global Thrombosis Test (Thromboquest Ltd., London, UK), which assesses thrombus formation and lysis under arterial flow conditions of high shear [29][30][31]. ...
Patients with transient ST-segment elevation myocardial infarction or spontaneous reperfusion, which occurs in approximately 20% of patients with ST-segment elevation myocardial infarction (STEMI), have smaller infarcts and more favourable clinical outcomes than patients without spontaneous reperfusion. Understanding the mechanisms underlying spontaneous reperfusion is therefore important, since this may identify possible novel therapeutic targets to improve outcomes in patients with STEMI. In this review, we discuss some of the possible determinants of spontaneous reperfusion including pro-thrombotic profile, endogenous fibrinolytic status, lipoprotein(a) (Lp(a)), inflammatory markers and neutrophil extracellular traps (NETs). Effective (rapid) endogenous fibrinolysis, as assessed in whole blood in vitro, using a point-of-care technique assessment of global thrombotic status, has been strongly linked to spontaneous reperfusion. Lp(a), which has a high degree of homology to plasminogen, may impair fibrinolysis through competitive inhibition of tissue plasminogen activator-mediated plasminogen activation as well as tissue plasminogen activator-mediated clot lysis and contributing to pathogenic clot properties by decreasing fibrin clot permeation. NETs appear to negatively modulate clot lysis by increasing thrombin fibre diameter and inhibiting plasmin-driven lysis of plasma clots. There are limited data that oral anticoagulation may modulate endogenous fibrinolysis but antiplatelet agents currently appear to have no impact. Phase III trials involving subcutaneous P2Y₁₂ or glycoprotein IIb/IIIa inhibitors, oral factor XIa inhibitors, interleukin-6 inhibitors, and apolipoprotein(a) antisense oligonucleotides in patients with cardiovascular disease are ongoing. Future studies will be needed to determine the impact of these novel antithrombotic, anti-inflammatory and lipid lowering therapies on endogenous fibrinolysis and spontaneous reperfusion.
