TY - GEN
T1 - Role of GP IIb/IIIa inhibitors on the fibrinolytic resistance of platelet-fibrin thrombi
AU - Huang, T. C.
AU - Jordan, R. E.
AU - Hantgan, R. R.
AU - Alevriadou, B. R.
PY - 1999
Y1 - 1999
N2 - The presence of platelets increases the fibrinolytic resistance of thrombi. When activated, platelets secrete PAI-1 and α2-antiplasmin and induce clot retraction. The search for potent antiplatelet agents has led to inhibitors of the platelet receptor GP IIb/IIIa, one of which is ReoPro (c7E3 Fab; abciximab). The effect of ReoPro on rt-PA-induced fibrinolysis was studied using an in vitro whole blood reperfusion model. When ReoPro was administered simultaneously with rt-PA at a wall shear rate of 500 s-1, it had no effect on the rate of fibrinolysis. rt-PA was found to lyse preformed gel-filtered platelet-fibrin substrates containing fixed platelets quicker than those containing normal platelets. ReoPro was shown to block platelet-fibrin interactions under arterial flow. Hence, we hypothesized (and are currently testing) that a combination of a GP IIb/IIIa inhibitor preincubated with the substrate, and a fibrinolytic drug injected with the flow, may hasten lysis of platelet-fibrin substrates under well-defined hemodynamic conditions. ReoPro may prove a necessary adjunctive treatment during thrombolytic therapy of platelet-rich thrombi.
AB - The presence of platelets increases the fibrinolytic resistance of thrombi. When activated, platelets secrete PAI-1 and α2-antiplasmin and induce clot retraction. The search for potent antiplatelet agents has led to inhibitors of the platelet receptor GP IIb/IIIa, one of which is ReoPro (c7E3 Fab; abciximab). The effect of ReoPro on rt-PA-induced fibrinolysis was studied using an in vitro whole blood reperfusion model. When ReoPro was administered simultaneously with rt-PA at a wall shear rate of 500 s-1, it had no effect on the rate of fibrinolysis. rt-PA was found to lyse preformed gel-filtered platelet-fibrin substrates containing fixed platelets quicker than those containing normal platelets. ReoPro was shown to block platelet-fibrin interactions under arterial flow. Hence, we hypothesized (and are currently testing) that a combination of a GP IIb/IIIa inhibitor preincubated with the substrate, and a fibrinolytic drug injected with the flow, may hasten lysis of platelet-fibrin substrates under well-defined hemodynamic conditions. ReoPro may prove a necessary adjunctive treatment during thrombolytic therapy of platelet-rich thrombi.
UR - https://www.scopus.com/pages/publications/0033342366
M3 - Conference contribution
AN - SCOPUS:0033342366
SN - 0780356756
T3 - Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
SP - 44
BT - Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
PB - IEEE
T2 - Proceedings of the 1999 IEEE Engineering in Medicine and Biology 21st Annual Conference and the 1999 Fall Meeting of the Biomedical Engineering Society (1st Joint BMES / EMBS)
Y2 - 13 October 1999 through 16 October 1999
ER -