From the Division of Cardiology (B.J.M.), Department of Medicine,
University Hospital Inselspital, Bern, Switzerland; The Mount Sinai Medical
Center (J.J.B., J.H.C., J.T.F., V.F.), New York, NY; and Cardiovascular
Research Center (L.B.), CSIC-H Sant Pau, Barcelona, Spain.
Correspondence to Beat J. Meyer, MD, Division of Cardiology, Department of Medicine, University Hospital Inselspital, 3010 Bern, Switzerland. E-mail bmeyer{at}insel.unibe.ch
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-1. Thrombus
formation was measured by morphometric analysis
(mm2/mm). The average size of a mural thrombus formed in 5
minutes was 0.14±0.03 mm2/mm. Progression of thrombus
growth within 10 minutes triggered by the preformed thrombus was
evaluated in pigs treated with r-hirudin (1 mg/kg per hour IV) as a
probe for thrombin, high-dose heparin (250 IU/kg per hour IV),
moderate-dose heparin (100 IU/kg per hour), moderate-dose heparin (100
IU/kg per hour) plus aspirin, aspirin alone (5 mg/kg IV), and placebo.
Hirudin was associated with a significant decrease (48%) of mural
thrombus area and significantly reduced growth of thrombus
(0.07±0.01), even compared with the highest dose of heparin
(0.15±0.03), although at lower levels of anticoagulation. Inhibition
of growth of thrombus with heparin was dose dependent, showing an
inverse correlation of thrombus area with mean plasma heparin
concentrations (r=.77, P=.0001). Thrombus
size was unchanged by aspirin (0.29±0.07) compared with controls
(0.28±0.07).
Conclusions—Direct inhibition of thrombin activity with r-hirudin
completely inhibits growth of thrombus, causes dissolution of a
preexisting mural thrombus, and is more effective at lower levels of
anticoagulation than the highest dose of heparin at shear rates typical
of a moderate coronary stenosis.
© 1998 American Heart Association, Inc.
Basic Science Reports
Dissolution of Mural Thrombus by Specific Thrombin Inhibition With r-Hirudin
Comparison With Heparin and Aspirin
Key Words: thrombus • hirudin • thrombosis • platelet aggregation inhibitors
This article has been cited by other articles:
 |
|
 |
|
  V. Fuster, P. R. Moreno, Z. A. Fayad, R. Corti, and J. J. Badimon Atherothrombosis and High-Risk Plaque: Part I: Evolving Concepts J. Am. Coll. Cardiol., September 20, 2005; 46(6): 937 - 954. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Vilahur, E. Segales, E. Salas, and L. Badimon Effects of a Novel Platelet Nitric Oxide Donor (LA816), Aspirin, Clopidogrel, and Combined Therapy in Inhibiting Flow- and Lesion-Dependent Thrombosis in the Porcine Ex Vivo Model Circulation, September 21, 2004; 110(12): 1686 - 1693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.A. Vorchheimer and V. Fuster Thrombin inhibitors in acute coronary artery disease Eur. Heart J., August 1, 2002; 23(15): 1142 - 1144. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Luciardi, S. Berman, J. Muntaner, F. De La Serna, and R. Altman Facilitated Thrombolysis: Dethrombosis? Clinical and Applied Thrombosis/Hemostasis, April 1, 2002; 8(2): 133 - 138. [Abstract] [PDF]
|
|
|
|
|
|
H. Mehta and B. J. Meyer r-Hirudin for percutaneous coronary interventions--time to reconsider? Eur. Heart J., January 2, 2002; 23(2): 95 - 97. [Full Text] [PDF]
|
|
|
|
|
|
S.R Mehta, J.W Eikelboom, H.-J Rupprecht, B.S Lewis, M.K Natarajan, C Yi, J Pogue, and S Yusuf Efficacy of hirudin in reducing cardiovascular events in patients with acute coronary syndrome undergoing early percutaneous coronary intervention Eur. Heart J., January 2, 2002; 23(2): 117 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Badimon, G. Vilahur, S. Sanchez, and X. Duran Atheromatous plaque formation and thrombogenesis: formation, risk factors and therapeutic approaches Eur. Heart J. Suppl., August 1, 2001; 3(suppl_I): I16 - I22. [Abstract] [PDF]
|
|
|
|
|
|
Y. Cottin, M. Kollum, R. Chan, B. Bhargava, Y. Vodovotz, and R. Waksman Vascular repair after balloon overstretch injury in porcine model effects of intracoronary radiation J. Am. Coll. Cardiol., October 1, 2000; 36(4): 1389 - 1395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Moshfegh, M. Redondo, F. Julmy, W. A. Wuillemin, M. U. Gebauer, A. Haeberli, and B. J. Meyer Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: enhanced inhibitory effects of combination therapy J. Am. Coll. Cardiol., September 1, 2000; 36(3): 699 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Peter, J. Graeber, S. Kipriyanov, M. Zewe-Welschof, M. S. Runge, W. Kubler, M. Little, and C. Bode Construction and Functional Evaluation of a Single-Chain Antibody Fusion Protein With Fibrin Targeting and Thrombin Inhibition After Activation by Factor Xa Circulation, March 14, 2000; 101(10): 1158 - 1164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Chesebro and J. J. Badimon Platelet Glycoprotein IIb/IIIa Receptor Blockade in Unstable Coronary Disease N. Engl. J. Med., May 21, 1998; 338(21): 1538 - 1541. [Full Text]
|
|