Is heparin treatment the optimal management for cerebral venous thrombosis? Effect of abciximab, recombinant tissue plasminogen activator, and enoxaparin in experimentally induced superior sagittal sinus thrombosis.
BACKGROUND
Based on a newly developed model of reversible superior sagittal sinus (SSS) thrombosis in the rat, we investigated the effect of thrombolytic and anticoagulant treatment on recanalization, brain parenchymal changes, and motor deficits.


METHODS
Thrombosis of the SSS was induced by topical application of ferric chloride. Occlusion was confirmed by magnetic resonance angiography (MRA). Six hours after operation, single treatment with 10 mg recombinant tissue plasminogen activator (rtPA)/kg and 6 mg abciximab/kg or subcutaneous injection of 450 IU/kg enoxaparin twice daily was started, each group containing 10 rats. Follow-up MRI with T2- and diffusion-weighted images was performed on the first, second, and seventh postoperative day.


RESULTS
Control and enoxaparin-treated animals developed diffuse brain edema without infarction or intracerebral bleeding. This was indicated by an increase of T2 relaxation time and a decrease of the apparent diffusion coefficient in the parasagittal and lateral cortex. In these groups, the degree of recanalization after 7 days was comparable (48% versus 52%). Enoxaparin-treated animals showed significant amelioration of functional deficits. Clinical outcome was best in the abciximab-treated group, with a residual sinus occlusion of 36% after 1 week. Highest recanalization was achieved by lysis with rtPA (85%).


CONCLUSIONS
Enoxaparin treatment in rats with cerebral venous thrombosis significantly influences clinical outcome. However, it has no effect on recanalization. GPIIb/IIIa antagonists and rtPA accelerate thrombolysis. They may represent an alternative in treatment of cerebral venous thrombosis.
Röttger
Carina
C
Department of Neurology, Justus-Liebig-University, Giessen, Germany.
Madlener
Katharina
K
Heil
Matthias
M
Gerriets
Tibo
T
Walberer
Maureen
M
Wessels
Tiemo
T
Bachmann
Georg
G
Kaps
Manfred
M
Stolz
Erwin
E
D000077284:Abciximab; D000792:Angiography; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000925:Anticoagulants / Q000627:therapeutic use*; D001792:Blood Platelets; D002712:Chlorides; D004195:Disease Models, Animal; D004487:Edema; D017984:Enoxaparin / Q000627:therapeutic use*; D005290:Ferric Compounds / Q000494:pharmacology; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D002542:Intracranial Embolism and Thrombosis / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D011994:Recombinant Proteins / Q000627:therapeutic use*; D020225:Sagittal Sinus Thrombosis / Q000188:drug therapy*; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000188:drug therapy*
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D002712:Chlorides; D017984:Enoxaparin; D005290:Ferric Compounds; D007140:Immunoglobulin Fab Fragments; D011994:Recombinant Proteins; D006493:Heparin; D010959:Tissue Plasminogen Activator; C024555:ferric chloride; D000077284:Abciximab