Evaluation of the mechanisms of antiepileptic drug-related chronic leukopenia.
Antiepileptic drug (AED)-related chronic leukopenia [white blood cell (WBC) count < 4,000/microliters] is a dilemma, especially when the AED is effective in controlling seizures. We evaluated the possible mechanisms of leukopenia in 7 patients. Mean WBC count was 3,000/microliters with a mean of 42% polymorphonuclear leukocytes (PMN). The AEDs were carbamazepine (CBZ) alone in 1 patient or CBZ combined with phenytoin (PHT), primidone (PRM), phenobarbital (PB) and/or valproate (VPA) in 5 patients; one patient was receiving PHT only. Bone marrow (BM) aspirates and PMN antibody studies using chemiluminescence were normal. Two liver-spleen scans 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 was decreased (54 +/- 10% in patients vs. 80 +/- 5% in controls: n = 13, p < 0.005). Our data, particularly the appropriate WBC response to the stress of exercise, and normal BM examinations suggest that continuation of AED therapy when leukopenia is stable and the percentage of PMN is normal is probably safe. Caution should be used if the absolute PMN count is consistently < 1,000/microliters. BM examinations need not be performed routinely for every patient with neutropenia due to AEDs, especially if the leukopenia fluctuates in the range of 2,000-4,000 cells/microliters.
O'Connor
C R
CR
Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School at Camden.
Schraeder
P L
PL
Kurland
A H
AH
O'Connor
W H
WH
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D002220:Carbamazepine / Q000009:adverse effects; D002448:Cell Adhesion / Q000187:drug effects; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy; D005260:Female; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D007970:Leukopenia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010672:Phenytoin / Q000009:adverse effects; D005082:Physical Exertion; D011324:Primidone / Q000009:adverse effects; D014635:Valproic Acid / Q000009:adverse effects
D000927:Anticonvulsants; D011324:Primidone; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin