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Flow-dependent channel formation in clots by an erythrocyte-bound fibrinolytic agent

Kathryn C. Gersh, Sergei Zaitsev, Douglas B. Cines, Vladimir Muzykantov, John W. Weisel

Abstract

Studies in animal models have shown that plasminogen activators bound to erythrocytes (RBC-PA) have an extended lifetime in the circulation and are safer than free PAs. RBC-PA incorporate into nascent thrombi which are focally lysed from within, an attractive thromboprophylactic option. In static systems, RBC-PA cleave surrounding fibrin fibers, forming pores larger than the cells themselves, and move around the pore edges, enlarging them until eventual clot dissolution. We hypothesized that under flow in blood vessels, RBC-PA form functional patent channels prior to clot dissolution. Here, we used perfusion chambers to study clot lysis by RBC-PA under static versus arterial and venous flow conditions. We found that flow decelerates bulk clot lysis but quickly generates patent channels filled with passing RBCs, via pore enlargement and merging in the direction of flow. Formation of such channels by RBC-PA may help rescue ischemic tissue before bulk dissolution of potentially occlusive clots.

  • Submitted October 4, 2010.
  • Accepted February 4, 2011.