Efficacy of tissue plasminogen activator in the lysis of thrombosis of the cerebral venous sinus

Abstract

Therapy for thrombo-occlusive disease of the cerebral venous sinuses remains controversial. Although several thrombolytic agents, such as urokinase and anticoagulants, are recommended for treatment, major significant risks include cerebral hemorrhage, especially in patients with venous infarction. Tissue plasminogen activator (tPA) has shown a high affinity for fibrin-bound plasminogen, while exhibiting a low affinity for circulating plasminogen. The purpose of this study was to evaluate this drug for use in cerebral sinus thrombo-occlusive disease. Eleven adult male rabbits were chosen as experimental animals. All animals underwent microsurgical dissection of their major dural venous sinuses. Direct compression was used to form a thrombus within the sinus. The presence of significant venous thrombosis was confirmed radiographically by iohexol sinography. Subsequently, tPA was delivered systemically via the marginal ear vein at a dose of 3000 units/h; the result was total lysis of the clot documented by a sinogram 1 hour after the drug was administered. Postmortem pathological examination confirmed total lysis in seven of eight animals. One animal showed partial retained clot fragments. No significant coagulopathic state was observed. In three control animals, saline was infused without clot lysis. We conclude that tPA is a highly effective agent for the lysis of acute induced venous sinus thrombosis in an experimental model.