Blood, Vol. 95 No. 5 (March 1), 2000:
pp. 1878-1879
CORRESPONDENCE
 |
Letter |
To the editor:
Acute priapism associated with the use of sildenafil
in a patient with sickle cell trait
Sildenafil, an oral agent that has proven effective for the
treatment of erectile dysfunction (ED), enables a natural erectile response to sexual stimulation by enhancing the relaxant effect of
nitric oxide (NO) on the corpora cavernosa. Normal penile erection may
involve the release of NO from nonadrenergic, noncholinergic nerves and
possibly endothelial cells of the cavernosal bodies. NO activates
guanylate cyclase, resulting in increased synthesis of cyclic guanosine
monophosphate (cGMP), which induces corpus cavernosal smooth muscle
relaxation, increased blood flow to the penis, increased
intracavernosal pressure, and penile erection. Sildenafil is a potent
inhibitor of cGMP-specific phosphodiesterase (PDE) type 5, which is the
predominant PDE isozyme responsible for the degradation of cGMP in the
corpora cavernosa. When the NO/cGMP pathway is activated, as occurs
with sexual stimulation, inhibition of PDE type 5 by sildenafil causes
increased concentrations of cGMP in the corpora cavernosa. Sexual
stimulation is required for sildenafil to produce its beneficial
pharmacological effects on erectile function.1
With the use of sildenafil, the most commonly reported adverse events
were headache, flushing, dyspepsia, rhinitis, and color perception disturbances that were all mild to moderate in nature. No
cases of priapism were reported with the use of sildenafil in
clinically controlled trials.1,2 Patients who have
conditions that may predispose them to priapism such as sickle cell
anemia, multiple myeloma, or leukemia are, however, advised to use
sildenafil with caution.3 We report here a case of priapism
in a patient with sickle cell trait associated with the use of sildenafil.
The patient is a 39-year-old male with sickle cell trait (AS) and a
past medical history that includes a subarachnoid cyst involving the
optic chiasma diagnosed in 1994 and Bell's Palsy/Ramsay Hunt
syndrome in 1997. The patient suffered head trauma from a motor
vehicle accident in 1998. The patient had sought urologic evaluation
for erectile dysfunction (ED) and was prescribed sildenafil. After
taking a dose of 50 mg, he had an erection within 15 minutes that was
sustained even after ejaculation. His erection became sustained and
painful for about 6 hours. The patient immediately noticed a loss of
morning erection followed by gradual worsening of his ED, with complete
loss of erection 3 months later.
Physical examination was not contributory. Laboratory evaluation
showed: WBC 4.90; Hb 15.1 g/dL; Hct 44.4%; MCV 88.6 fl; Platelet 216/nL. Hormonal determinations revealed: FSH 3.0 mIU/mL (nl 1-8); LH
3.6 mIU/mL (nl 2-12); serum prolactin 14.3 µcg/L (nl 3.00-19.0); testosterone 304 ng/dL (nl 262-1593). Hemoglobin (Hb) electrophoresis, isoelectric focusing, and globin separation by denaturing high performance liquid chromatography (HPLC) were
consistent with sickle cell trait. Use of those three different methods
should detect mutations with charge differences. Red cell separation by
isopycnic density gradient that can detect alterations in mean corpuscular hemoglobin concentration (MCHC) that would
predispose toward polymer formation5 was consistent with
sickle cell trait. Mass spectroscopy can detect electrophoretically
silent mutations of Hb. In this case, it revealed only the presence of
globin chains with molecular weights corresponding to 
,
A, and S, as would be expected in sickle
cell trait. We therefore conclude that the patient has sickle trait and
has no detectable globin or red cell-based predisposition for polymer
formation beyond that which is expected in sickle trait.
Priapism as a complication of sickle cell anemia is a well-known
phenomenon, but has not been associated with sickle cell trait. The
lifetime incidence of priapism in patients with sickle cell
anemia was found to be about 45% in homozygous patients (HbSS) in
a Jamaican study.4 Sickle cell disease is a condition
with very varied phenotypic expression in patients with the
same genetic defect.6
Patients with sickle cell trait are spared the major complications
associated with sickle cell anemia, but a subset of AS individuals
develop minor complications such as hyposthenuria (loss of ability of
the kidneys to concentrate urine), splenic infarcts when exposed to
hypoxic conditions or at high altitudes, and papillary
necrosis.7 In addition, AS individuals are at risk for the
rare occurrence of renal basal tubular carcinoma.8 The
possibility thus exists that patients with sickle cell trait that
suffer these complications might have gene modifiers (epistatic genes)
that increase the risk for these pleiotropic phenotypic traits.
The effects of sildenafil lead to prolonged relaxation of smooth
muscles in the corpora cavernosa and hence restoration of the natural
erectile response to sexual stimulation. Nevertheless, the associated
stagnation of blood within the corpora cavernosa results in
local hypoxia, and in SS individuals the degree of deoxygenation may be
sufficient to lead to erythrocytic rigidity and sickling, which can
lead to priapism.9 To our knowledge, this complication has
not been reported in AS individuals. The susceptibility of a patient
with sickle trait to this condition might also depend on the effects of
inherited modifier genes, which are yet to be identified.
Physicians should be aware of the possibility of sildenafil causing
priapism in patients with sickle cell trait, although we do not know
the incidence rate of this event. In the meantime, the manufacturers
should advise against the use of this drug in sickle trait individuals
until more data are obtained.
Adetola A. Kassim
Mary E. Fabry
Ronald L. Nagel
Division of Hematology, Department of Medicine, Albert Einstein
College of Medicine/Montefiore Medical Center, Bronx, NY
| |
References |
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