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INTERVENTIONAL CARDIOLOGY

Monocyte-derived tissue factor contributes to stent thrombosis in an in vitro system

Tullio Palmerini, MD^*,*, Barry S. Coller, MD, Vittorio Cervi, BSc^*, Luciana Tomasi, BSc^*, Antonio Marzocchi, MD^*, Cinzia Marrozzini, MD^*, Ornella Leone, MD, Milena Piccioli, BSC and Angelo Branzi, MD^*

^* Istituto di Cardiologia
Istituto di Anatomia Patologica, Policlinico S. Orsola, University of Bologna, Bologna, Italy
Laboratory of Blood and Vascular Biology, Rockefeller University, New York, New York

Manuscript received March 25, 2004; revised manuscript received July 2, 2004, accepted July 12, 2004.

^* Reprint requests and correspondence: Dr. Tullio Palmerini, Istituto di Cardiologia, Università di Bologna, Policlinico S. Orsola, Via Massarenti 9, 40138 Bologna, Italy (Email: tulliopalmerini{at}hotmail.com).

OBJECTIVES: This study evaluated the role of circulating tissue factor (TF) in mediating thrombus formation on stents in an in vitro model of stent perfusion.

BACKGROUND: The traditional view of coagulation has recently been challenged by the demonstration that TF is present in circulating blood. The potential contribution of this intravascular pool of TF to thrombus formation on stents is not known.

METHODS: Coronary stents were placed in parallel silicone tubes connected to a roller pump that was set to pump blood at a flow rate of 10 ml/min. Stents were then exposed to heparinized blood from healthy volunteers for 120 min.

RESULTS: The presence of the stent in the circuit caused a significant increase in monocyte TF expression, but only monocytes with attached platelets stained positive for TF. Thrombi formed on stents and the thrombi stained positive for TF. Pretreatment of blood with a monoclonal antibody against TF (cH36) caused a 56% reduction in ¹²⁵I-fibrin(ogen) deposition on stents compared with controls (p = 0.002). Monocyte depletion of blood reduced ¹²⁵I-fibrin(ogen) deposition by 45% (p = 0.01) and TF staining in the thrombus by 83% (p = 0.01). Pretreatment of blood with a monoclonal antibody against P-selectin reduced ¹²⁵I-fibrin(ogen) deposition by 24% (p = 0.04). Perfusion of stents with leukocyte-reduced platelet-rich plasma (PRP) produced small thrombi and treatment of PRP with cH36 reduced ¹²⁵I-fibrin(ogen) deposition by 43% (p = 0.01).

CONCLUSIONS: Circulating TF plays a pivotal role in thrombus formation on stents. Monocytes appear to be the main, but not only, source of TF depositing in the thrombus.

Abbreviations and Acronyms   IOD = integrated optical density   Mab = monoclonal antibody   MRB = monocyte-reduced blood   PPP = platelet-poor plasma   PRP = platelet-rich plasma   TF = tissue factor

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