Fibrinolysis therapy achieved with tissue plasminogen activator and aspiration of the liquefied clot after experimental intracerebral hemorrhage: rapid reduction in hematoma volume but intensification of delayed edema formation

Abstract

Object. Fibrinolysis therapy accomplished using tissue plasminogen activator (tPA) and aspiration is considered to be a viable alternative to microsurgery and medical therapy for the treatment of deep-seated spontaneous intracerebral hematomas (SICHs). Tissue plasminogen activator is a mediator of thrombin- and ischemia-related delayed edema. Because both thrombin release and ischemia occur after SICH, the authors planned to investigate the effect of fibrinolytic therapy on hematoma and delayed edema volume. Methods. A spherical hematoma was created in the frontal white matter of 18 pigs. In the tPA-treated group (nine pigs), a mean of 1.55 ml tPA was injected into the clot and the resulting liquefied blood was aspirated. Magnetic resonance (MR) imaging was performed on Days 0 (after surgery), 4, and 10, and the volumes of hematoma and edema were determined. In the animals not treated with tPA (untreated group; nine pigs), the volume of hematoma dropped from 1.43 ± 0.42 ml on Day 0 to 0.85 ± 0.28 ml on Day 10. In the tPA-treated group, the volume of hematoma was reduced from 1.51 ± 0.28 ml on Day 0 to 0.52 ± 0.39 ml on Day 10. In comparison with the untreated group, the reduction in hematoma volume was significantly accelerated (p = 0.02). In the untreated group, perihematomal edema increased from 0.32 ± 0.61 ml to 1.73 ± 0.73 ml on Day 4, before dropping to 1.17 ± 0.92 ml on Day 10. In the tPA-treated group, the volume of the edema increased from 0.09 ± 0.21 ml on Day 0 to 1.93 ± 0.79 ml on Day 4, and further to 3.34 ± 3.21 ml on Day 10. The increase in edema volume was significantly more pronounced in the tPA-treated group (p = 0.04). Conclusions. Despite a significantly accelerated reduction in hematoma volume, the development of delayed perifocal edema was intensified by fibrinolytic therapy, which is probably related to the function of tPA as a mediator of edema formation after thrombin release and ischemia. Further experimental and clinical investigations are required to establish the future role of fibrinolysis in the management of SICH.