English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Periprocedural thrombus formation is not only responsible for one of the most serious complications of percutaneous transluminal coronary angioplasty, acute thrombotic occlusion of the coronary artery, but has also been postulated as the initial trigger of pathophysiological mechanisms leading to restenosis. The latter hypothesis is based on experimental findings showing that thrombin activation stimulates mitogenesis and cell growth in cultured fibroblasts and smooth muscle cells. Furthermore, empirical data in patients with unstable angina, in whom coronary thrombus formation following initial plaque disruption is frequently present, have shown a worse acute outcome and increased restenosis rates after percutaneous transluminal coronary angioplasty. For these reasons, antithrombotic therapy with heparin and antiplatelet agents have become established as standard treatment for patients undergoing percutaneous transluminal coronary angioplasty. Heparin is an effective antithrombotic agent that primarily acts by catalyzing the inactivation of thrombin and activated factor X by antithrombin III. Therefore, heparin needs the plasma protein antithrombin III to function as an inhibitor of thrombin. Systemic or local antithrombin deficiency might limit the antithrombotic effectiveness of heparin during percutaneous transluminal coronary angioplasty. Indeed, depletion of antithrombin III activity was demonstrated repeatedly in patients with unstable angina by several authors and is responsible for reduced efficacy of heparin resulting in acute thrombus formation after percutaneous transluminal coronary angioplasty. Accordingly, Schachinger et alP investigated whether an intracoronary infusion of antithrombin III during percutaneous transluminal coronary angioplasty might reduce acute thrombotic occlusion. The result failed to indicate a significant reduction. These authors therefore felt that antithrombin III would not play an important role in this setting and that platelet activation and aggregation were mainly responsible for local thrombus formation and thrombotic occlusion after percutaneous transluminal coronary angioplasty. Unfortunately, patients were not investigated as regards late clinical outcome in this study. In the present issue, Grip and co-workers investigated the possible influence of a dose-adjusted systemic antithrombin III infusion (with a targeted antithrombin III plasma level of 120%) on a hypercoagulable state, as well as on acute thrombotic complications and late restenosis rate in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty. They found no significant differences in dose-adjusted antithrombin III infusion coagulation activation markers, for example prothrombin fragments F,+2, thrombin-a2 antithrombin complexes (TAT) and soluble fibrin. However, fibrin D-dimer plasma concentration was significantly reduced on days 3 and 4 in the antithrombin Ill-treated group. The authors considered these findings were the result of lower thrombin activation and therefore less secondary activation of the endogenous fibrinolytic system in antithrombin Ill-treated patients. There was no influence on acute outcome after percutaneous transluminal coronary angioplasty, including thrombotic occlusion, in the antithrombin Ill-treated group. The restenosis rate was not significantly lower in the antithrombin Ill-treated group, but a trend to a reduced restenosis incidence was seen. This may be because there was less coagulation activation in the antithrombin Ill-treated group. Our understanding of the cellular and molecular mechanisms of restenosis remains limited. Restenosis is believed to result primarily from a 'response to injury' of the interventional trauma and from subsequent disturbed wound healing. Disproportional activation of one or more physiological woundhealing responses may result in poorly controlled and therefore persistent pathological reactivation, instead of self-limited and favourable vascular remodelling. These responses include platelet activation and aggregation, thrombin formation, cell recruitment and activation, cell proliferation, matrix synthesis and tissue contraction. At present no clear information is available about the definite role of thrombin formation in unstable patients with percutaneous transluminal coronary angioplasty and restenosis, although some hypothetical conclusions can be drawn and are worthy of discussion. We cannot exclude the possibility that periprocedural thrombin formation is a prominent contributor to restenosis, even though no relationship has been found between an increase in direct (TAT, F,+2) and a decrease in indirect biochemical markers (DDimer) of thrombin activation and the development of late restenosis'. These biochemical markers of thrombin generation are too sensitive to differentiate

Adjunctive infusion of antithrombin III during percutaneous transluminal coronary angioplasty