EVALUATION OF THE MECHANISMS OF ANTIEPILEPTIC DRUG-RELATED CHRONIC LEUKOPENIA

Antiepileptic drug (AED)-related chronic leukopenia [white blood cell (WBC) count <4,000/mu l] is a dilemma, especially when the AED is effe ctive in controlling seizures. We evaluated the possible mechanisms of leukopenia in 7 patients. Mean WBC count was 3,000/mu l with a mean o f 42% polymorphonuclear leukocytes (PMN). The AEDs were carbamazepine (CBZ) alone in 1 patient or CBZ combined with phenytoin (PHT), primido ne (PRM), phenobarbital (PB) and/or valproate (VPA) in 5 patients; one patient was receiving PHT only. Bone marrow (BM) aspirates and PMN an tibody studies using chemiluminescence were normal. Two liver-spleen s cans showed mild relative splenomegaly. After exercise, WBC count(n = 7) increased by 54% (SEM 12%), while the WBC counts in controls (n = 5 ) increased by 52 +/- 16%. Antinuclear antibodies (Hep-2) were absent in 6 patients and positive (1:160) in 1. PMN adhesion to nylon wool wa s decreased (54 +/- 10% in patients vs. 80 +/- 5% in controls: n = 13, p < 0.005). Our data, particularly the appropriate WBC response to th e stress of exercise, and normal BM examinations suggest that continua tion of AED therapy when leukopenia is stable and the percentage of PM N is normal is probably safe. Caution should be used if the absolute P MN count is consistently <1,000/mu l. BM examinations need not be perf ormed routinely for every patient with neutropenia due to AEDs, especi ally if the leukopenia fluctuates in the range of 2,000-4,000 cells/mu l.