German research comparing different treatment strategies for cerebral venous thrombosis (CVT) suggests that the glycoprotein (GP) IIb/IIIa antagonist abciximab and recombinant tissue plasminogen activator (rtPA) may be effective alternatives to enoxaparin.
"Preliminary uncontrolled investigations suggest that thrombolysis may be more effective than intravenous heparin therapy, which is widely accepted for treatment of CVT," note Carina Röttger (Justs-Liebig-University, Giessen) and colleagues. "The role of platelets in the pathogenesis of CVT has not yet been studied systematically," they add.
To investigate further, the team used a newly developed rat model of superior sagittal sinus (SSS) thrombosis to compare the effects of thrombolytic and anticoagulant treatment on recanalization, brain parenchymal changes, and motor deficits. Thrombosis was induced by the topical application of ferric chloride in a surgically exposed SSS, and magnetic resonance imaging (MRI) was used to confirm occlusion.
After 6 hours, the rats were assigned to receive a single 10 mg/kg dose of rtPA, 6 mg/kg of abciximab, or 450 IU/kg of enoxaparin, administered twice daily. Additionally, a control group of rats had SSS thrombosis induced, but were untreated.
Follow-up MRI scans, including T2- and diffusion-weighted images, were performed 1, 2, and 7 days postoperatively.
Reporting their results in the journal Stroke, Röttger et al say that both control and enoxaparin treated animals showed a significantly reduced T2-RT relaxation time, indicating the development of diffuse brain edema. Occlusion levels after 7 days were similar in both of these groups, at 48% and 52%, respectively.
In contrast, occlusion levels were significantly lower in animals treated with abciximab and rtPA after 7 days, at 36% and 15%, respectively.
The researchers note, however, that animals treated with enoxaparin displayed a significant improvement in functional deficits.
While observing that it has no effect on recanalization, the authors conclude: "Enoxaparin treatment in rats with CVT significantly influences clinical outcome."
They add: "GP IIb/IIIa antagonists and rtPA accelerate thrombolysis. They may represent an alternative in treatment of cerebral venous thrombosis."