Clozapine-induced blood
dyscrasias
Eduardo D. Trinidad,* Anil Potti,* Syed A. Mehdi°
*Department of Medicine and °Division of Hematology,
Veterans Affairs Medical Center, University of North Dakota School
of Medicine and Health Sciences, 1919 N Elm Street, Fargo, ND
58102, USA
Correspondence: Anil Potti MD, Department of Medicine, University
of North Dakota School of Medicine and Health Sciences, 1919 N Elm
Street, Fargo, ND 58102, USA. Phone: international +1.701.
293-4132. Fax: international +1.701.293-4145. E-mail:
anilpotti@meritcare.com
We read with interest the
article by Deliliers in
the recent issue of Hematologica. It was interesting to
note his findings, which would suggest a lower than expected rate
of life-threatening leukopenia associated with clozapine
use.1 Although the author had stated that paradoxical
leukocytosis and eosinophilia might be observed, he had also
mentioned that they are usually transient. We present an atypical
case of persistent leukocytosis thought to be secondary to
clozapine use in an effort to add to the literature on the
side-effect profile of this drug commonly used in patients with
schizophrenia and schizo-affective disorders. As in our case, the
diagnosis may sometimes be difficult, since patients may be on
other mood altering drugs that may also have an effect on blood
cell counts.
A 41-year-old caucasian male was admitted to the psychiatric ward
from the emergency department on March 4, 2000 for "violent
thoughts." He had been diagnosed as having paranoid schizophrenia
at 28 years of age. A chart review revealed that in his initial
clinical course, the patient's paranoid ideation and violent
behavior resulted in several trials of various antipsychotic
medications including thioridazine and lithium, which were used
intermittently with limited benefit. In April 1992, the patient
was ultimately placed on clozapine, providing the best management
of his schizophrenia to this date with good control of the
patient's paranoid behavior. Risperidone and buspirone were added
later as mood-stabilizing agents.
During his current hospitalization, the patient was afebrile with
normal vital signs. General and systemic examination were
remarkable for cushingoid features, the rest of the examination
was normal. He had an elevated white cell count of 22.3 x 103
(K) cells/cmm (81% neutrophils). Hemogram revealed a
hematocrit of 45.3%, MCV of 89.2 fL, and platelet count of 270,000
mL. The high white cell count prompted a consult to hematology.
Detailed chart review indicated that the leukocytosis was chronic
in nature dating back eight years to the initiation of clozapine
therapy. He had a normal white blood count prior to starting
clozapine in 1992 and the white blood count has remained
moderately elevated until the present time in a range from 15.4 K
cells/cmm to 24.4 K cells/cmm (Figure
1). A peripheral smear
showed a normochromic, normocytic picture with no nucleated blood
cells and normal white cell maturation with leukocytosis and
neutrophilia. No source of occult infection was identified. The
patient continued to be asymptomatic. Given that the chronic
leukocytosis was considered benign and patient seemed to have the
best response to clozapine, the recommendation to the psychiatric
service was to continue management with clozapine and lithium and
continued monitoring of cell counts. Clozapine is an atypical
antipsychotic agent, the use of which has been limited by its
tendency to cause agranulocytosis.2 Clozapine-induced
neutropenia is thought to be secondary to a cytotoxic effect on
the committed progenitor cell compartment but not on primitive
hematopoietic cells.3 This effect has also been shown
to be more pronounced with N-desmethylclozapine.
Leukocytosis, monocytosis, eosinophilia and lymphopenia are other
blood dyscrasias that have been sporadically reported with
clozapine use.4,5 Most of these side-effects have been
thought to be transient and dose-dependent.5,6 Although
it is likely that in our patient concurrent lithium therapy may be
a contributing factor to,7 the temporal profile between
initiation of clozapine use and onset of leukopenia implicates
clozapine as the primary cause of leukocytosis. It is also to be
noted that patients on therapy with lithium in addition to
clozapine may have 'persistent' leukocytosis. The exact mechanism
of clozapine-induced leukocytosis is not known but knowledge of
this phenomenon may prevent unnecessary evaluation of leukocytosis
in such patients. Our case is the first reported case of
'persistent' leukocytosis secondary to clozapine therapy in a
patient being treated with lithium. Also, it delineates the
practical difficulties in determining a cause for drug-induced
blood dyscrasias in psychiatric patients who frequently are
dependent on more than one mood altering agent in the management
of their disease state.
