Abstracts

RATIONALE: Much attention has been paid to the possibility of a bleeding diathesis due to valproate (e.g. Zeller et al., Epilepsia 1999;40:186-9; Anderson et al., J Neurosurg 1997;87:252-6). To our knowledge, no reports have surfaced of possible bleeding complications due to any of the newer anticonvulsants. A dramatic case at our center of hemorrhagic complication (index case) of epilepsy surgery in a patient on levetiracetam prompted a review of our surgical cases for any other possible levetiracetam-associated hemorrhages.
METHODS: A retrospective chart review of all epilepsy surgeries performed at our institution in the past three years was initiated. Hemorrhagic complication was defined as hematoma, bleeding requiring transfusion, bleeding requiring premature termination of the initial surgical procedure, or a repeat procedure to address bleeding. Cases were considered to be associated with levetiracetam if it was being received at the time of surgery or had been discontinued the day before surgery. Each chart was also reviewed for other possible causes of bleeding (DIC, underlying coagulation disorder, etc.).
RESULTS: Three cases were uncovered, all unexplained. Two were in the context of levetiracetam therapy. The first case (index case) had had previous surgeries (off LVT) without complications. He was noted to have significant oozing at the time of subdural electrode implantation, although pre-op screen was normal. LVT was stopped to provoke seizures and he went for resection 7 days later without excess bleeding. Pre-op medications, LVT and OXC, were resumed that evening. The next day he developed subural, epidural, and subgaleal hemorrhage, requiring reoperation. LVT has not been resumed; extensive w/u for known coagulopathies was negative. The second case had a subdural hematoma requiring multiple procedures to control. The third patient was in status on pentobarbital and propofol; subdural strips could not be placed due to bleeding.
Two more cases of bleeding abnormalities without surgical complications were detected: a patient on levetiracetam, lamotrigine and topiramate had persistently abnormal coagulation studies with negative hematologic evaluation; the second, on lamotrigine and topiramate, had significant oozing at surgery insufficient to meet the above criteria.
CONCLUSIONS: In clinical trials, levetiracetam altered leukocyte levels, produced a significant increase in frequency of upper respiratory tract infections, and produced statistically significant but clinically trivial decreases in erythrocyte count (Harden, Epilepsia 2001;42[suppl.4]:36-39). The possibility may exist that levetiracetam has a subtle effect on megakaryocytes, producing a previously unappreciated bleeding diathesis.
Our findings suggest a higher than expected association between levetiracetam treatment and hemorrhagic complications of epilepsy surgery in our center[ssquote]s series of patients. We are continuing our analysis to permit calculation of relative risk versus other anticonvulsants. We urge other surgical centers to review their own experience for any evidence of levetiracetam-associated hemorrhagic complications. (Disclosure: Grant - Werz MA: GlaxoSmithKline, Consulting - Werz MA: GlaxoSmithKline, Honoraria - Werz MA: GlaxoSmithKline Swartz B: GlaxoSmithKline, UCB-Pharma, Ortho-McNeil, Novartis)