0022-5347'91 '1451-0065S02.00/0
THEJOURKAL O F UROLOGY Copyright C 1991 b y AMERICAN CBOLOGICAL ASSOCIATION, INC
Vol. 145, 65-58. January 1991 Printed in C'S A.
PRIAPISM ASSOCIATED WITH THE SICKLE CELL HEMOGLOBINOPATHHES: PREVALENCE, NATURAL HISTORY AND SEQUELAE JACKSON E. FOWLER, JR.,* MABEL MOSHY, MICHAEL STRUB
AND
STEPHEN K. CNINN
From the Division of Urology and Section of Hematology, University of Illinois College of Medicine, Chicago, Illinois
ABSTRACT
T o determine the prevalence and characteristics of priapism associated with sickle cell hemoglobinopathic conditions we interviewed and examined 52 men with sickle cell anemia, 10 with sickle C disease, 3 with sickle B+-thalassemia and 19 with sickle cell trait. Of the men 20 with sickle cell anemia (38%) and 1 with sickle Bt-thalassemia (33%) reported past priapism attacks. Average patient age at onset in the sickle cell anemia patients was 19 years (range 8 to 30 years). Four men had had only 1 attack. The average number of attacks per year in the remaining patients ranged from 1 to 52. Of the patients who reported multiple attacks the average duration of a typical episode and the duration of the longest self-limiting episode was 1.6 and 7.0 hours, respectively. Six patients had experienced 1 attack that persisted for longer than 24 hours. There were no significant differences between the clinical and hematological parameters of the sickle cell anemia patients who did and did not experience priapism or of the priapism patients who had and had not experienced episodes lasting greater than 24 hours. Six patients had been hospitalized for priapism and 4 were treated with a shunting procedure. Of the latter patients 2 were impotent but there was no significant alteration in the sexual function of the other study participants. KEYWORDS:priapism; penis; anemia, sickle cell
Sickle cell hemoglobinopathic conditions result from inheritance of 1 or 2 genes that code for the abnormal S hemoglobin.' Approximately 0.15% of all black Americans are homoz~gous for hemoglobin S and have sickle cell anemia, and approximately 8% are heterozygous and have sickle cell trait. In addition, some black Americans inherit the hemoglobin S gene and a second gene that codes for another such as the B+-thalassemia or C hemoglobin. Chronic hemolytic anemia and recurrent vaso-occlusive events that produce painful crises and ischemic tissue injury are the principal clinical manifestations of sickle cell anemia. The vaso-occlusive phenomena result from decreased erythrocyte pliability and capillary obstruction, and may lead to avascular bone necrosis, retinopatkic conditions, cutaneous ulceration of the lower extremities, and impaired pulmonary, hepatic, cardiac and renal function. The ischemic complications of sickle cell anemia are unusual in patients with sickle cell trait but may be seen in patients with sickle B+-thalassemia and sickle C disease, Priapism is another complication of sickle cell anemia. It is believed that the stagnation of blood within the sinusoids of the corpora cavernosa during a physiological erection increases erythroc~rterigidity and impairs the venous outflow from the corporeal bodies. Prolongation of the erection and pain induced by ischemia of the corporeal tissues are potential consequences of these events. Of the men who seek medical attention for the treatment of priapism to 20% have sickle the prevalence, natural history and sequelae of priapism in men with sickle cell anemia are poorly defined, and data concerning the prevalence of priapism in men with the other sickle cell hemoglobinopathic conditions are not available. We interviewed and examined men with sickle cell hemoglobinopathic conditions to develop insights into these issues.
tinely attended a comprehensive adult sickle cell clinic and 19 consecutive men with sickle cell trait who were hospitalized at our institution for unrelated illnesses during the study period participated in the investigation. The nature of the hemoglobinopathic condition in each patient had been established by hemoglobin electrophoresis with cellulose acetate, ,-itrate agar solubility testing and quantitative chromatography. Steady state hematological parameters and information concerning the clinical manifestations of the hemoglobinopathic conditions were obtained from the clinical records. The data are summarized in Interview and examination. Each participant was interviewed and examined by a who had knowledge of the medical history of the individual. Priapism was defined as an unwanted, sustained erection lasting 30 minutes or longer. A standardized questionnaire was used to determine the estimated frequency of the priapism episodes, the duration of a typical episode and of the longest remembered episode, events that appeared to precipitate the attacks, maneuvers used to terminate the attacks, the necessity for hospitalization to manage attacks and treatments during the hospitalization. In addition, each participant was asked to compare the quality of currenterections with those obtained during the sexual experiences. However, no attempts were made to confirm the validity of this assessment with objective tests. The physical examination was limited to the external genitalia and focused upon palpable abnormalities of the corporeal bodies that might result from repeated priapism episodes. Statistical analysis. Statistical testing was done with the chi'quare and t tests.
'.
RESULTS
One or more priapism episodes were reported by 20 of the men with sickle cell anemia (38%),1with sickle B+-thalassemia (33%) but none with sickle cell trait or sickle C disease. The majority of patients with sickle cell anemia were aware that priapism was a potential complication of the disorder and all patients who had had priapism recognized that the event was abnormal.
MATERIALS A N D METHODS
Patients. A total of 65 consecutive men with sickle cell anemia, sickle B+-thalassemia and sickle C disease who rouAccepted for publication June 12, 1990. * Requests for reprints: Division of Urology, University of Illinois College of Medicine, Box 6998, Chicago, Illinois 60680. 65
F O W L E R A N D ASSOCIATES
TABLE1. Characteristics of patients studied Sickle C disease
Sickle Cell Anemia
Sickle Bt thalassemia
Sickle Cell Trait
No. pts. Age (range)* No. with painful crises (%) No. painful crises per yr.* No. with chronic ischemic complica. tions (%) Hemoglobin (gm./dl.)* % hemoglobin S* % hemoglobin F* % hemoglobin A*
* Mean + 1standard deviation
The clinical and hematological characteristics of the men with sickle cell anemia who had and had not experienced priapism are shown in table 2. None of the parameters in the 2 patient groups was significantly different (p >0.05). When stratified by patient age a t interview and examination the proportion of patients with a history of priapism ranged from 0 to 60% (fig. 1).However, the prevalence of priapism in each of the age groups was not significantly different (p >0.05). The first priapism episode among the men with sickle cell anemia occurred when they were 8 to 30 years old (table 3). Only 2 men (10%) had the first attack during the first decade of life. Of the men 4 (20%) had experienced only I episode at 2, 4, 5 and 5 years before the interview. The interval since the first priapism episode among the men with multiple attacks ranged from 1to 33 years and all but 2 impotent men had had a t least 1 attack during the preceding 12 months. The yearly incidence of multiple priapism episodes ranged from I to 52 and the intervals between attacks were relatively constant for each patient. Clustering of the attacks was not reported. The duration of a typical episode ranged from 30 minutes to 6 hours and was also relatively uniform for each patient. The longest
TABLE3. Characteristics o f ~ r i a a i s mi n m e n with sickle cell anemia Age (yrs.) at first episode (range)' No. with only 1 episode (96) No. with multiple episodes (96) Yrs. since first episode (range)? Annual incidence of episodes (range)? Hrs. of typical episode (range)? Hrs. of longest self-limiting episode (range)t Usual precipitating events (%):$ Sleep Normal daytime activity Normal sexual arousal Cigarette smoking Anesthesia Alcohol ingestion Marijuana use Usual maneuvers to resolve episodes (%):$ Bed rest Analgesics Showers Hydration Ejaculation Exercise
* Mean f 1 standard deviation.
t Mean + 1 standard deviation among men with multiple episodes.
$No. among men with multiple episodes, some patients had more than 1 event.
TABLE 2. Characteristics o f m e n with sickle cell anemia who had and had not exwerienced wriawism No. pts. Age (yrs.)* Hemoglobin (gm./dl.)* % hemoglobin F* Reticulocyte count (%I* Mean corpuscular vol. (fl.)* No. painful crises per yr." No. with chronic ischemic complications (%)
20 28.2 7.2 8.8 f 1.0 3.6 f 2.6 11.8 4.4 89 f 9 16.6 f 21.3 12 (60)
+
+
* Mean + 1 standard deviation.
10-15
16-20
21-25
26-30
31-35
36-40
41-45
age FIG. 1. Prevalence of priapism relative t o age in men with sickle cell anemia.
self-limiting episode remembered by each patient ranged from 1to 48 (mean 7.4) hours. There were no correlations between the average number of priapism episodes per year and the duration of a typical episode or of the longest episode that was self-limiting or treated during hospitalizations (fig. 2). Six men, including 1 who had experienced only 1 episode, had an attack that lasted for 24 hours or longer. With the exception of 2 patients who became impotent, these individuals continued to have priapism of a frequency and duration that paralleled that experienced before the prolonged episode. There were no significant differences in the clinical or hematological parameters of patients who did and did not have an episode that exceeded 24 hours (data not shown). In a majority of cases the priapism episodes usually occurred during sleep and awoke the patient because of penile discomfort (table 3). Normal sexual arousal was the most common precipitating event among the patients who had priapism during the waking hours. However, no provoking event could be identified by more than 40% of the men who usually had attacks during the waking hours. A variety of self-administered treatments or maneuvers were believed to promote resolution of the priapism attacks and I or more were used routinely by the men who experienced multiple episodes. Six patients were hospitalized on 1 occasion each for the treatment of a priapism episode. The duration of the episode that prompted hospital admission ranged from 1%hours to 7 days (fig. 2). The patients were managed at other institutions and the details of treatment were not available. However, 4 patients underwent a shunting procedure: 3 by the technique of Nelson and Winter,3 and 1 by creation of a cavernousspongiosum shunt.
PRIAPISM ASSOCIATED W;TH SICKLE CELL, E ~ ~ E M O G E B B I N O P A T E ~ E ~
Single
1-3 12-24 Average Numkr Episode%p r Year
62
FIG. 2. Duration o f typical and longest priapism episodes and average yearly frequency of priapism episodes in men with sickle cell anemia. 1, episode that necessitated hospitalization but that was not treated surgically. 2, episode managed b y shunting procedure with subsequent potency. 3, episode managed by shunting procedure with subsequent impotence.
O f t h e m e n treated w i t h a W i n t e r shunt 2 have been unable t o obtain a n erection since t h e procedure. I n addition, 2 patients w i t h sickle cell anemia and priapism w h o had never been hospitalized, and 2 w i t h n o history o f priapism had functionally insignificant penile deviation during erection. N o n e o f t h e other study participants reported erectile dysfunction or erections t h a t differed from t h e earliest sexual experiences. O f t h e sickle cell anemia patients with priapism who had not undergone a shunting procedure only 1had palpable induration o f t h e corpora cavernosa. None o f t h e other study participants w h o had n o t undergone a shunting procedure, including t h e 4 m e n w i t h penile deviation during erection, had palpable abnormalities o f t h e corpora cavernosa. T h e patient w i t h sickle B+-thalassemia and priapism had 71% hemoglobin S and had experienced 1 attack per year for 2 years before t h e interview. T h e attacks were self-limiting, lasted for 45 and 90 minutes, and did not require hospitalization. DISCUSSION
T h i s investigation demonstrates t h a t priapism is a c o m m o n complication o f sickle cell anemia. Our observations concerning t h e characteristics o f t h e priapism attacks were necessarily limited t o patient recall and should b e viewed as estimates only. Nonetheless, all o f t h e participants seemed t o appreciate t h e opportunity t o discuss t h e problem i n detail and expressed confidence i n t h e accuracy o f t h e responses. T h e participants were recruited f r o m a n established adult sickle cell clinic and
67
t h e manifestations o f the disease m a y have been more pronounced t h a n i n t h e general population o f m e n with sickle cell anemia. A bias introduced b y t h i s selection process is unquantifiable. Finally, m a n y o f t h e participants were young adults and t h e potential adverse sequelae o f multiple priapism attacks throughout adult life are necessarily indeterminate. Notably, however, our data do not suggest t h a t sexual dysfunction is more c o m m o n in middle-aged m e n with sickle cell anemia t h a n i n young m e n with t h e disorder. W e found t h a t t h e priapism associated w i t h sickle cell anemia is unusual before puberty. T h i s is consistent with t h e reported 6% prevalence o f priapism i n children w i t h sickle cell anemia.4 Most o f t h e affected patients had repeated episodes t h a t lasted for less t h a n 3 hours and a majority o f t h e attacks occurred during sleep. T h i s phenomenon m a y result f r o m t h e physiological dehydration and metabolic acidosis t h a t accompany sleep and t h a t increase t h e rigidity o f erythrocytes i n patients w i t h sickle cell anemia. Anesthesia, marijuana use and alcohol ingestion, which have been reported as inciting causes o f priapism in m e n w i t h sickle cell anemia: were unusual causes o f priapism i n our ~ a t i e n t s . M a n y o f our observations are similar t o those made b y E m o n d et a1 i n a survey o f 104 Jamaican m e n with sickle cell T h e prevalence o f priapism i n t h e Jamaican patients was 42%. Median patient age at onset was 21 years a n d only 4 patients had attacks during t h e first decade o f life. Of t h e patients 57% experienced multiple attacks (more t h a n 10) t h a t usually lasted for less t h a n 3 hours and 31% had o n l y 1 or 2 attacks. Over-all, 27% o f the patients had episodes t h a t lasted for longer t h a n 24 hours. T h e s e major attacks occurred i n patients with infrequent and frequent episodes, and i n some cases constituted t h e only reported episode. Other aspects o f t h e Jamaican study, however, were n o t substantiated b y this experience. Emond et al reported t h a t self-limiting priapism was generally episodic i n nature and t h a t a cluster o f attacks o f t e n culminated i n a n episode t h a t lasted for greater t h a n 24 hours. Priapism after t h e long-lived episodes was uncommon. I n contrast, our patients reported a relatively constant pattern o f self-limiting episodes t h a t i n m a n y cases were more frequent t h a n those in t h e Jamaican m e n , and t h e 4 patients who remained potent after a n attack o f 24 hours or longer continued t o have episodes o f t h e same frequency and duration as those before the prolonged attack. It also is notable t h a t t h e median age o f the Jamaican patients (22 years) paralleled t h a t o f our patient population b u t 27% o f t h e Jamaican m e n w i t h priapism complained o f partial or complete impotence. T h i s complication was reported b y only 10% o f t h e affected patients i n our investigation, a difference t h a t m a y reflect a n increased availability o f medical care i n Chicago t h a n i n Jamaica. Hematological parameters t h a t correlated significantly w i t h a history o f priapism i n the Jamaican study included a decreased level o f hemoglobin F and an increased platelet count. Patients who experienced major attacks had a decreased level o f hemoglobin F , a lower reticulocyte count and a higher m e a n corpuscular volume t h a n the patients who did n o t report major attacks. W e also found that t h e level o f hemoglobin F among t h e sickle cell anemia patients w i t h priapism was lower t h a n i n t h e patients without priapism but t h e difference was n o t statistically significant. T h e r e also were n o differences i n t h e h e matological parameters among t h e priapism patients w h o did and did not have attacks that lasted for 24 hours or longer. However, t h e platelet counts were not recorded i n our study and fewer patients were interviewed. O n l y 1 o f t h e participants i n our study w h o did n o t have sickle cell anemia experienced priapism. T h i s individual had sickle B+-thalassemia, a hemoglobinopathic condition t h a t is characterized b y relatively high levels o f hemoglobin S. T h e number o f patients w i t h sickle C disease or sickle cell trait was limited, and w e are aware o f 2 m e n with sickle C disease w h o
68
F O W L E R AND ASSOCIATES
REFERENCES had previously attended the clinic and complained of prolonged, painful erections. For these reasons our findings are best inter1. Bunn, H. F.: Disorders of hemoglobin. In: Harrison's Principles of preted as evidence that priapism is an unusual complication of Internal Medicine, 11th ed. Edited by E. Brauwald, K. J. sickle C disease and sickle cell trait. Isselbacher, R. G. Petersdorf, J. D. Wilson, J . B. Martin and A. This report does not concern the optimal management of S. Fauci. New York: McGraw-Hill Book Co., vol. 2, chapt. 288, priapism in men with sickle cell hemoglobinopathic conditions pp. 1518-1524,1987. but some of the findings have considerable therapeutic rele2. Pohl, J., Pott, B. and Kleinhans, G.: Priapism: a three-phase vance. Due to the frequency and self-limiting nature of priapism concept of management according to aetiology and prognosis. Brit. J. Urol., 58:113, 1986. in men with sickle cell anemia conservative measures, such as 3. Nelson, J. H., I11 and Winter, C. C.: Priapism: evolution of manhydration, alkalization, exchange transfusions to decrease the agement in 48 patients in a 22-year series. J. Urol., 11'9:455, level of hemoglobin S to 30 to 40% and intracavernous injec1977. tions of an a-adrenergic agent,5,7-galways should be considered 4. Tarry, W. F., Duckett, J. W., Jr. and Synder, H. McC., 111: Urologbefore interventional treatments are performed. This is particical complications of sickle cell disease in a pediatric population. ularly true if the duration of the erection before hospital adJ. Urol., 138:592, 1987. mission is less than 6 hours. On the other hand, there are no 5. Broderick, G. A. and Lue, T. F.: Priapism and the physiology of reliable data concerning the duration of priapism and the risks . erection. AUA Update Series, vol. VII, lesson 29, 1988. of impotence, and shunting procedures do not necessarily lead 6. Emond, A. M., Holman, R., Hayes, R. J. and Sergeant, G. R.: to i m p ~ t e n c e The . ~ timing of surgical intervention in patients Priapism and impotence in homozygous sickle cell disease. Arch. who are refractory to conservative management, therefore, Intern. Med., 140:1434, 1980. must necessarily be left to clinical judgment. 7. Baron, M. and Leiter, E.: The management of priapism in sickle An important byproduct of this experience was the realizacell anemia. J. Urol., 119: 610, 1978. tion that most men with sickle cell anemia had misconceptions 8. Conrad, M. E., Perrine, G. M., Barton, J. C. and Durant, J. R.: concerning the nature of available treatments for priapism and Provoked priapism in sickle cell anemia. Amer. J. Hematol., 9: the indications for medical evaluation. We now spend more 121, 1980. time discussing these issues with our patients and encourage 9. Seeler, R. A,: Priapism in children with sickle cell anemia: successful management with liberal red cell transfusions. Clin. Ped., medical attention for attacks that persist for longer than 4 to 10:418, 1971. 6 hours.
THEJOURKAL O F UROLOGY Copyright C 1991 b y AMERICAN CBOLOGICAL ASSOCIATION, INC
Vol. 145, 65-58. January 1991 Printed in C'S A.
PRIAPISM ASSOCIATED WITH THE SICKLE CELL HEMOGLOBINOPATHHES: PREVALENCE, NATURAL HISTORY AND SEQUELAE JACKSON E. FOWLER, JR.,* MABEL MOSHY, MICHAEL STRUB
AND
STEPHEN K. CNINN
From the Division of Urology and Section of Hematology, University of Illinois College of Medicine, Chicago, Illinois
ABSTRACT
T o determine the prevalence and characteristics of priapism associated with sickle cell hemoglobinopathic conditions we interviewed and examined 52 men with sickle cell anemia, 10 with sickle C disease, 3 with sickle B+-thalassemia and 19 with sickle cell trait. Of the men 20 with sickle cell anemia (38%) and 1 with sickle Bt-thalassemia (33%) reported past priapism attacks. Average patient age at onset in the sickle cell anemia patients was 19 years (range 8 to 30 years). Four men had had only 1 attack. The average number of attacks per year in the remaining patients ranged from 1 to 52. Of the patients who reported multiple attacks the average duration of a typical episode and the duration of the longest self-limiting episode was 1.6 and 7.0 hours, respectively. Six patients had experienced 1 attack that persisted for longer than 24 hours. There were no significant differences between the clinical and hematological parameters of the sickle cell anemia patients who did and did not experience priapism or of the priapism patients who had and had not experienced episodes lasting greater than 24 hours. Six patients had been hospitalized for priapism and 4 were treated with a shunting procedure. Of the latter patients 2 were impotent but there was no significant alteration in the sexual function of the other study participants. KEYWORDS:priapism; penis; anemia, sickle cell
Sickle cell hemoglobinopathic conditions result from inheritance of 1 or 2 genes that code for the abnormal S hemoglobin.' Approximately 0.15% of all black Americans are homoz~gous for hemoglobin S and have sickle cell anemia, and approximately 8% are heterozygous and have sickle cell trait. In addition, some black Americans inherit the hemoglobin S gene and a second gene that codes for another such as the B+-thalassemia or C hemoglobin. Chronic hemolytic anemia and recurrent vaso-occlusive events that produce painful crises and ischemic tissue injury are the principal clinical manifestations of sickle cell anemia. The vaso-occlusive phenomena result from decreased erythrocyte pliability and capillary obstruction, and may lead to avascular bone necrosis, retinopatkic conditions, cutaneous ulceration of the lower extremities, and impaired pulmonary, hepatic, cardiac and renal function. The ischemic complications of sickle cell anemia are unusual in patients with sickle cell trait but may be seen in patients with sickle B+-thalassemia and sickle C disease, Priapism is another complication of sickle cell anemia. It is believed that the stagnation of blood within the sinusoids of the corpora cavernosa during a physiological erection increases erythroc~rterigidity and impairs the venous outflow from the corporeal bodies. Prolongation of the erection and pain induced by ischemia of the corporeal tissues are potential consequences of these events. Of the men who seek medical attention for the treatment of priapism to 20% have sickle the prevalence, natural history and sequelae of priapism in men with sickle cell anemia are poorly defined, and data concerning the prevalence of priapism in men with the other sickle cell hemoglobinopathic conditions are not available. We interviewed and examined men with sickle cell hemoglobinopathic conditions to develop insights into these issues.
tinely attended a comprehensive adult sickle cell clinic and 19 consecutive men with sickle cell trait who were hospitalized at our institution for unrelated illnesses during the study period participated in the investigation. The nature of the hemoglobinopathic condition in each patient had been established by hemoglobin electrophoresis with cellulose acetate, ,-itrate agar solubility testing and quantitative chromatography. Steady state hematological parameters and information concerning the clinical manifestations of the hemoglobinopathic conditions were obtained from the clinical records. The data are summarized in Interview and examination. Each participant was interviewed and examined by a who had knowledge of the medical history of the individual. Priapism was defined as an unwanted, sustained erection lasting 30 minutes or longer. A standardized questionnaire was used to determine the estimated frequency of the priapism episodes, the duration of a typical episode and of the longest remembered episode, events that appeared to precipitate the attacks, maneuvers used to terminate the attacks, the necessity for hospitalization to manage attacks and treatments during the hospitalization. In addition, each participant was asked to compare the quality of currenterections with those obtained during the sexual experiences. However, no attempts were made to confirm the validity of this assessment with objective tests. The physical examination was limited to the external genitalia and focused upon palpable abnormalities of the corporeal bodies that might result from repeated priapism episodes. Statistical analysis. Statistical testing was done with the chi'quare and t tests.
'.
RESULTS
One or more priapism episodes were reported by 20 of the men with sickle cell anemia (38%),1with sickle B+-thalassemia (33%) but none with sickle cell trait or sickle C disease. The majority of patients with sickle cell anemia were aware that priapism was a potential complication of the disorder and all patients who had had priapism recognized that the event was abnormal.
MATERIALS A N D METHODS
Patients. A total of 65 consecutive men with sickle cell anemia, sickle B+-thalassemia and sickle C disease who rouAccepted for publication June 12, 1990. * Requests for reprints: Division of Urology, University of Illinois College of Medicine, Box 6998, Chicago, Illinois 60680. 65
F O W L E R A N D ASSOCIATES
TABLE1. Characteristics of patients studied Sickle C disease
Sickle Cell Anemia
Sickle Bt thalassemia
Sickle Cell Trait
No. pts. Age (range)* No. with painful crises (%) No. painful crises per yr.* No. with chronic ischemic complica. tions (%) Hemoglobin (gm./dl.)* % hemoglobin S* % hemoglobin F* % hemoglobin A*
* Mean + 1standard deviation
The clinical and hematological characteristics of the men with sickle cell anemia who had and had not experienced priapism are shown in table 2. None of the parameters in the 2 patient groups was significantly different (p >0.05). When stratified by patient age a t interview and examination the proportion of patients with a history of priapism ranged from 0 to 60% (fig. 1).However, the prevalence of priapism in each of the age groups was not significantly different (p >0.05). The first priapism episode among the men with sickle cell anemia occurred when they were 8 to 30 years old (table 3). Only 2 men (10%) had the first attack during the first decade of life. Of the men 4 (20%) had experienced only I episode at 2, 4, 5 and 5 years before the interview. The interval since the first priapism episode among the men with multiple attacks ranged from 1to 33 years and all but 2 impotent men had had a t least 1 attack during the preceding 12 months. The yearly incidence of multiple priapism episodes ranged from I to 52 and the intervals between attacks were relatively constant for each patient. Clustering of the attacks was not reported. The duration of a typical episode ranged from 30 minutes to 6 hours and was also relatively uniform for each patient. The longest
TABLE3. Characteristics o f ~ r i a a i s mi n m e n with sickle cell anemia Age (yrs.) at first episode (range)' No. with only 1 episode (96) No. with multiple episodes (96) Yrs. since first episode (range)? Annual incidence of episodes (range)? Hrs. of typical episode (range)? Hrs. of longest self-limiting episode (range)t Usual precipitating events (%):$ Sleep Normal daytime activity Normal sexual arousal Cigarette smoking Anesthesia Alcohol ingestion Marijuana use Usual maneuvers to resolve episodes (%):$ Bed rest Analgesics Showers Hydration Ejaculation Exercise
* Mean f 1 standard deviation.
t Mean + 1 standard deviation among men with multiple episodes.
$No. among men with multiple episodes, some patients had more than 1 event.
TABLE 2. Characteristics o f m e n with sickle cell anemia who had and had not exwerienced wriawism No. pts. Age (yrs.)* Hemoglobin (gm./dl.)* % hemoglobin F* Reticulocyte count (%I* Mean corpuscular vol. (fl.)* No. painful crises per yr." No. with chronic ischemic complications (%)
20 28.2 7.2 8.8 f 1.0 3.6 f 2.6 11.8 4.4 89 f 9 16.6 f 21.3 12 (60)
+
+
* Mean + 1 standard deviation.
10-15
16-20
21-25
26-30
31-35
36-40
41-45
age FIG. 1. Prevalence of priapism relative t o age in men with sickle cell anemia.
self-limiting episode remembered by each patient ranged from 1to 48 (mean 7.4) hours. There were no correlations between the average number of priapism episodes per year and the duration of a typical episode or of the longest episode that was self-limiting or treated during hospitalizations (fig. 2). Six men, including 1 who had experienced only 1 episode, had an attack that lasted for 24 hours or longer. With the exception of 2 patients who became impotent, these individuals continued to have priapism of a frequency and duration that paralleled that experienced before the prolonged episode. There were no significant differences in the clinical or hematological parameters of patients who did and did not have an episode that exceeded 24 hours (data not shown). In a majority of cases the priapism episodes usually occurred during sleep and awoke the patient because of penile discomfort (table 3). Normal sexual arousal was the most common precipitating event among the patients who had priapism during the waking hours. However, no provoking event could be identified by more than 40% of the men who usually had attacks during the waking hours. A variety of self-administered treatments or maneuvers were believed to promote resolution of the priapism attacks and I or more were used routinely by the men who experienced multiple episodes. Six patients were hospitalized on 1 occasion each for the treatment of a priapism episode. The duration of the episode that prompted hospital admission ranged from 1%hours to 7 days (fig. 2). The patients were managed at other institutions and the details of treatment were not available. However, 4 patients underwent a shunting procedure: 3 by the technique of Nelson and Winter,3 and 1 by creation of a cavernousspongiosum shunt.
PRIAPISM ASSOCIATED W;TH SICKLE CELL, E ~ ~ E M O G E B B I N O P A T E ~ E ~
Single
1-3 12-24 Average Numkr Episode%p r Year
62
FIG. 2. Duration o f typical and longest priapism episodes and average yearly frequency of priapism episodes in men with sickle cell anemia. 1, episode that necessitated hospitalization but that was not treated surgically. 2, episode managed b y shunting procedure with subsequent potency. 3, episode managed by shunting procedure with subsequent impotence.
O f t h e m e n treated w i t h a W i n t e r shunt 2 have been unable t o obtain a n erection since t h e procedure. I n addition, 2 patients w i t h sickle cell anemia and priapism w h o had never been hospitalized, and 2 w i t h n o history o f priapism had functionally insignificant penile deviation during erection. N o n e o f t h e other study participants reported erectile dysfunction or erections t h a t differed from t h e earliest sexual experiences. O f t h e sickle cell anemia patients with priapism who had not undergone a shunting procedure only 1had palpable induration o f t h e corpora cavernosa. None o f t h e other study participants w h o had n o t undergone a shunting procedure, including t h e 4 m e n w i t h penile deviation during erection, had palpable abnormalities o f t h e corpora cavernosa. T h e patient w i t h sickle B+-thalassemia and priapism had 71% hemoglobin S and had experienced 1 attack per year for 2 years before t h e interview. T h e attacks were self-limiting, lasted for 45 and 90 minutes, and did not require hospitalization. DISCUSSION
T h i s investigation demonstrates t h a t priapism is a c o m m o n complication o f sickle cell anemia. Our observations concerning t h e characteristics o f t h e priapism attacks were necessarily limited t o patient recall and should b e viewed as estimates only. Nonetheless, all o f t h e participants seemed t o appreciate t h e opportunity t o discuss t h e problem i n detail and expressed confidence i n t h e accuracy o f t h e responses. T h e participants were recruited f r o m a n established adult sickle cell clinic and
67
t h e manifestations o f the disease m a y have been more pronounced t h a n i n t h e general population o f m e n with sickle cell anemia. A bias introduced b y t h i s selection process is unquantifiable. Finally, m a n y o f t h e participants were young adults and t h e potential adverse sequelae o f multiple priapism attacks throughout adult life are necessarily indeterminate. Notably, however, our data do not suggest t h a t sexual dysfunction is more c o m m o n in middle-aged m e n with sickle cell anemia t h a n i n young m e n with t h e disorder. W e found t h a t t h e priapism associated w i t h sickle cell anemia is unusual before puberty. T h i s is consistent with t h e reported 6% prevalence o f priapism i n children w i t h sickle cell anemia.4 Most o f t h e affected patients had repeated episodes t h a t lasted for less t h a n 3 hours and a majority o f t h e attacks occurred during sleep. T h i s phenomenon m a y result f r o m t h e physiological dehydration and metabolic acidosis t h a t accompany sleep and t h a t increase t h e rigidity o f erythrocytes i n patients w i t h sickle cell anemia. Anesthesia, marijuana use and alcohol ingestion, which have been reported as inciting causes o f priapism in m e n w i t h sickle cell anemia: were unusual causes o f priapism i n our ~ a t i e n t s . M a n y o f our observations are similar t o those made b y E m o n d et a1 i n a survey o f 104 Jamaican m e n with sickle cell T h e prevalence o f priapism i n t h e Jamaican patients was 42%. Median patient age at onset was 21 years a n d only 4 patients had attacks during t h e first decade o f life. Of t h e patients 57% experienced multiple attacks (more t h a n 10) t h a t usually lasted for less t h a n 3 hours and 31% had o n l y 1 or 2 attacks. Over-all, 27% o f the patients had episodes t h a t lasted for longer t h a n 24 hours. T h e s e major attacks occurred i n patients with infrequent and frequent episodes, and i n some cases constituted t h e only reported episode. Other aspects o f t h e Jamaican study, however, were n o t substantiated b y this experience. Emond et al reported t h a t self-limiting priapism was generally episodic i n nature and t h a t a cluster o f attacks o f t e n culminated i n a n episode t h a t lasted for greater t h a n 24 hours. Priapism after t h e long-lived episodes was uncommon. I n contrast, our patients reported a relatively constant pattern o f self-limiting episodes t h a t i n m a n y cases were more frequent t h a n those in t h e Jamaican m e n , and t h e 4 patients who remained potent after a n attack o f 24 hours or longer continued t o have episodes o f t h e same frequency and duration as those before the prolonged attack. It also is notable t h a t t h e median age o f the Jamaican patients (22 years) paralleled t h a t o f our patient population b u t 27% o f t h e Jamaican m e n w i t h priapism complained o f partial or complete impotence. T h i s complication was reported b y only 10% o f t h e affected patients i n our investigation, a difference t h a t m a y reflect a n increased availability o f medical care i n Chicago t h a n i n Jamaica. Hematological parameters t h a t correlated significantly w i t h a history o f priapism i n the Jamaican study included a decreased level o f hemoglobin F and an increased platelet count. Patients who experienced major attacks had a decreased level o f hemoglobin F , a lower reticulocyte count and a higher m e a n corpuscular volume t h a n the patients who did n o t report major attacks. W e also found that t h e level o f hemoglobin F among t h e sickle cell anemia patients w i t h priapism was lower t h a n i n t h e patients without priapism but t h e difference was n o t statistically significant. T h e r e also were n o differences i n t h e h e matological parameters among t h e priapism patients w h o did and did not have attacks that lasted for 24 hours or longer. However, t h e platelet counts were not recorded i n our study and fewer patients were interviewed. O n l y 1 o f t h e participants i n our study w h o did n o t have sickle cell anemia experienced priapism. T h i s individual had sickle B+-thalassemia, a hemoglobinopathic condition t h a t is characterized b y relatively high levels o f hemoglobin S. T h e number o f patients w i t h sickle C disease or sickle cell trait was limited, and w e are aware o f 2 m e n with sickle C disease w h o
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REFERENCES had previously attended the clinic and complained of prolonged, painful erections. For these reasons our findings are best inter1. Bunn, H. F.: Disorders of hemoglobin. In: Harrison's Principles of preted as evidence that priapism is an unusual complication of Internal Medicine, 11th ed. Edited by E. Brauwald, K. J. sickle C disease and sickle cell trait. Isselbacher, R. G. Petersdorf, J. D. Wilson, J . B. Martin and A. This report does not concern the optimal management of S. Fauci. New York: McGraw-Hill Book Co., vol. 2, chapt. 288, priapism in men with sickle cell hemoglobinopathic conditions pp. 1518-1524,1987. but some of the findings have considerable therapeutic rele2. Pohl, J., Pott, B. and Kleinhans, G.: Priapism: a three-phase vance. Due to the frequency and self-limiting nature of priapism concept of management according to aetiology and prognosis. Brit. J. Urol., 58:113, 1986. in men with sickle cell anemia conservative measures, such as 3. Nelson, J. H., I11 and Winter, C. C.: Priapism: evolution of manhydration, alkalization, exchange transfusions to decrease the agement in 48 patients in a 22-year series. J. Urol., 11'9:455, level of hemoglobin S to 30 to 40% and intracavernous injec1977. tions of an a-adrenergic agent,5,7-galways should be considered 4. Tarry, W. F., Duckett, J. W., Jr. and Synder, H. McC., 111: Urologbefore interventional treatments are performed. This is particical complications of sickle cell disease in a pediatric population. ularly true if the duration of the erection before hospital adJ. Urol., 138:592, 1987. mission is less than 6 hours. On the other hand, there are no 5. Broderick, G. A. and Lue, T. F.: Priapism and the physiology of reliable data concerning the duration of priapism and the risks . erection. AUA Update Series, vol. VII, lesson 29, 1988. of impotence, and shunting procedures do not necessarily lead 6. Emond, A. M., Holman, R., Hayes, R. J. and Sergeant, G. R.: to i m p ~ t e n c e The . ~ timing of surgical intervention in patients Priapism and impotence in homozygous sickle cell disease. Arch. who are refractory to conservative management, therefore, Intern. Med., 140:1434, 1980. must necessarily be left to clinical judgment. 7. Baron, M. and Leiter, E.: The management of priapism in sickle An important byproduct of this experience was the realizacell anemia. J. Urol., 119: 610, 1978. tion that most men with sickle cell anemia had misconceptions 8. Conrad, M. E., Perrine, G. M., Barton, J. C. and Durant, J. R.: concerning the nature of available treatments for priapism and Provoked priapism in sickle cell anemia. Amer. J. Hematol., 9: the indications for medical evaluation. We now spend more 121, 1980. time discussing these issues with our patients and encourage 9. Seeler, R. A,: Priapism in children with sickle cell anemia: successful management with liberal red cell transfusions. Clin. Ped., medical attention for attacks that persist for longer than 4 to 10:418, 1971. 6 hours.
