Relative efficacy of antithrombin compared with antiplatelet agents in accelerating coronary thrombolysis and preventing early reocclusion.

Haskel, Ethan J.; Prager, Nelson A.; Sobel, Burton E.; Abendschein, Dana R.

doi:10.1161/01.cir.83.3.1048

Cited by 137 publications

(47 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34 However, if r-hirudin is administered in combination with thrombolytic agents (rt-PA), residual platelet-rich thrombus may be eliminated at lower levels of anticoagulation (aPTT ratios, 2.5 times control). 10 In experimental studies of coronary thrombosis, hirudin was superior to heparin in facilitating thrombolysis with both t-PA and streptokinase 10,39,40 and almost completely eliminated residual platelet-rich thrombus. 10 Dissolution of mural thrombus by specific thrombin inhibiton with r-hirudin is of potential therapeutic benefit after acute coronary syndromes that could lead to improved vessel patency with reduced stenosis, thus decreasing the need for revascularization procedures in a significant proportion of patients.…”

Section: Discussionmentioning

confidence: 99%

Dissolution of Mural Thrombus by Specific Thrombin Inhibition With r-Hirudin

Meyer

Badimon²,

Chesebro³

et al. 1998

Circulation

View full text Add to dashboard Cite

Background-The presence of residual mural thrombus may predispose to recurrent thrombotic events in acute coronary syndromes. The purpose of this study was to evaluate the effects of antithrombotic and antiplatelet agents on a preformed, fresh mural thrombus during growth of thrombus. Methods and Results-A fresh mural thrombus was formed by perfusing severely injured arterial wall with porcine blood for 5 minutes at a shear rate of 1690 s

show abstract

Section: Discussionmentioning

confidence: 99%

Dissolution of Mural Thrombus by Specific Thrombin Inhibition With r-Hirudin

Meyer

Badimon²,

Chesebro³

et al. 1998

Circulation

View full text Add to dashboard Cite

show abstract

“…It is, however, not easy to directly compare the results from different studies with experimental coronary thrombosis. The techniques for inducing the thrombus have varied from study to study, and the experimental protocol concerning the mode of drug administration, dose levels, and imaging the thrombus and its lysis has also varied between studies [166][167][168][169][170][171].…”

Section: Thrombolysis and Carboxypeptidase U Inhibition -Paper IVmentioning

confidence: 99%

Inhibition of carboxypeptidase U (TAFIa) activity improves rt-PA induced thrombolysis in a dog model of coronary artery thrombosis

Björkman

Abrahamsson

Nerme

et al. 2005

Thrombosis Research

View full text Add to dashboard Cite

The physiologically most important activator of intravascular fibrinolysis is tissue-type plasminogen activator (t-PA) released from endothelial cells. In man, sympathomimetic drugs increase the systemic concentration of t-PA. It is therefore of interest to investigate whether cardiac sympathetic activation can induce a local t-PA release, which could counteract intra-coronary clot formation.Thrombolytic therapy with recombinant t-PA (rt-PA) is effective in acute myocardial infarction, but the treatment is limited by a fairly slow reperfusion rate and frequent early reocclusions. A potential mechanism behind early reocclusions might be that active thrombin is released from the thrombus during thrombolytic therapy. Thrombin has recently been shown to activate procarboxypeptidase U, which in its active form (CPU) down-regulates endogenous fibrinolysis. Therefore, one way of improving thrombolytic efficacy may be to combine rt-PA with a lowmolecular weight direct thrombin inhibitor, which theoretically could have a pro-fibrinolytic effect, either by inhibition of fibrin-bound thrombin and/or by inhibition of CPU activation. An alternative way may be direct inhibition of CPU.In a porcine model, experimental activation of cardiac sympathetic nerves by electrical stimulation at 1 and 8 Hz induced 5-and 20-fold increase in the release of both total and active t-PA together with frequency-dependent increases in heart rate, blood pressure, and coronary blood flow. The t-PA release was independent of the heart rate and coronary flow response, but local infusion of isoprenaline suggested that part of the t-PA response was mediated by stimulation of β-adrenergic receptors. Next, we studied the combined effect of rt-PA and thrombin inhibitors (melagatran, hirudin and heparin) in a canine model of copper coil-induced coronary thrombosis. The profibrinolytic effect of rt-PA, either measured as patency rate or time-to-patency, was significantly enhanced with the low-molecular weight direct thrombin inhibitor melagatran, but to a lesser degree by hirudin and heparin. In the same model it was shown that active CPU is produced locally in the coronary vascular bed during both thrombus formation and clot lysis. Inhibition of thrombin attenuated CPU formation and improved patency. A similar effect was obtained with a direct inhibitor of CPU.In conclusion, the coronary t-PA response to sympathetic stimulation may constitute a thromboprotective defence mechanism to counteract its prothrombotic effects on the systemic level. Furthermore, direct thrombin and/or CPU inhibition may be potential targets for prevention of thrombus formation via facilitation of the endogenous fibrinolytic system.

show abstract

“…6 Animal studies and clinical observations suggest that increased thrombin activity and platelet aggregation, both amenable to control by pharmacological agents, may be involved in the occurrence of reocclusion. [7][8][9] Thus, understanding the mechanisms that regulate platelet reactivity may lead to better prevention and treatment of ischemic heart disease. Fluid dynamic forces may be relevant in this regard, because blood flow through stenotic atherosclerotic arteries results in extremely elevated shear rates.…”

mentioning

confidence: 99%

Enhanced Shear-Induced Platelet Aggregation in Acute Myocardial Infarction

et al. 1999

View full text Add to dashboard Cite

Background-Experiments under controlled flow conditions indicate that the binding of von Willebrand factor (vWF) to platelet glycoprotein (GP) Ib␣ and integrin ␣ IIb ␤ 3 (GP IIb/IIIa complex) is crucial for aggregation at elevated shear rates. We have tested how the plasma of patients with acute myocardial infarction affects this process. Methods and Results-Citrated plasma was obtained from 18 patients with acute myocardial infarction within 6 hours from the onset of symptoms and from 26 control subjects with chest pain syndrome without evidence of ischemia. Aggregation of normal platelets at high shear rates was significantly greater in the presence of patient than control plasma and was inhibited by both anti-GP Ib␣ and anti-␣ IIb ␤ 3 monoclonal antibodies. The observed values (meanϮSD) were 47.6Ϯ17.8% versus 30.1Ϯ9.9% at 10 800 s Ϫ1 (PϽ0.01) and 32.9Ϯ14.1% versus 17.5Ϯ9.5% at 7200 s Ϫ1 (PϽ0.01), respectively, and were positively correlated with plasma vWF antigen levels and ristocetin cofactor activities. In contrast, at the lower shear rate of 1200 s Ϫ1 , aggregation was similar in the presence of control or patient plasma and was not inhibited by the anti-GP Ib␣ antibody. Both vWF antigen and platelet aggregation decreased 2 weeks after the onset of myocardial infarction. Conclusions-Shear-induced platelet aggregation is enhanced in plasma in the presence of acute myocardial infarction, apparently as a result of increased vWF concentration. This may contribute to the onset of acute coronary artery thrombosis and early reocclusion after reperfusion treatment. (Circulation. 1999;99:608-613.)

show abstract

Relative efficacy of antithrombin compared with antiplatelet agents in accelerating coronary thrombolysis and preventing early reocclusion.

Cited by 137 publications

References 44 publications

Dissolution of Mural Thrombus by Specific Thrombin Inhibition With r-Hirudin

Dissolution of Mural Thrombus by Specific Thrombin Inhibition With r-Hirudin

Inhibition of carboxypeptidase U (TAFIa) activity improves rt-PA induced thrombolysis in a dog model of coronary artery thrombosis

Enhanced Shear-Induced Platelet Aggregation in Acute Myocardial Infarction

Contact Info

Product

Resources

About