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Keywords:

  • priapism;
  • sickle-cell anaemia;
  • erectile dys-function;
  • survey

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Authors

Objective  To define the incidence, risk factors and complications of priapism in a large population of patients with sickle-cell anaemia in five centres in the UK and Nigeria, as priapism is common among these patients, but the precise characteristics of the condition in this population are poorly documented.

Patients and methods  A questionnaire was developed and administered to patients with sickle-cell disease. Questions were designed to define the incidence, nature, precipitants, duration, treatment and complications of priapism. A distinction was made between acute (severe) priapism and the recurrent, ‘stuttering’ type.

Results  The questionnaire was completed by 130 patients (mean age 25 years, sd 11, range 4–66) from the five centres; 102 (78%) were homozygous Hb SS genotype, 19 (15%) were Hb SC genotype and two (1.5%) were Hb Sα−thalassaemia. Of the patients, 46 (35%) reported a history of priapism, and of these, 33 (72%) had a history of stuttering priapism, while 24 (52%) had had an acute episode of priapism. The mean age of onset of priapism was 15 years, with 75% of patients having the first episode before their 20th birthday. Sexual activity was the most frequent precipitating factor, with fever and/or dehydration being the next most common. Of the 46 patients, 10 (21%) with a history of priapism reported having erectile dysfunction. A similar proportion reported dissatisfaction with sexual intercourse, including a fear of engaging in sexual activity.

Conclusion  The incidence of priapism among patients with sickle-cell anaemia is high (35%). The implications of priapism for erectile and sexual function are significant and documented in this large series. The treatment of this condition in these patients remains unstandardised. This study highlights the need for an increased awareness of the problems associated with priapism among patients, families and medical professionals.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Authors

Priapism is a condition of painful, purposeless, persistent penile erection, first described by Tripe [1] in 1845, and first associated with sickle-cell disease in 1934 [2]. Classically, two types of priapism are described, i.e. low-flow (ischaemic) and high-flow (not ischaemic), referring to the relative oxygenation of the blood in the corpora cavernosa. The former is painful and blood-gas analysis reveals hypoxia. Priapism in sickle-cell anaemia is a typical form of the low-flow type.

Priapism is known to be a common problem among male patients with sickle-cell disease. The physiology of normal penile erection has been reviewed elsewhere [3]. The precise mechanism of priapism in patients with sickle-cell disease remains unclear. The assumed mechanism is that normal erection decreases the oxygen tension in the corpora cavernosa, predisposing to erythrocyte sickling [4]. The sickled erythrocytes predispose to venous stasis, which therefore perpetuates the priapism. Cavernosography shows that this stasis results in obstruction of the deep dorsal penile vein [5]. An inflammatory reaction follows which results in fibrosis of the spongy trabeculae, which probably leads to subsequent impotence.

Earlier reports suggested that the prevalence of priapism was 2–6%[6]; this information was based predominantly on hospital admission data, with its limitations. In a study of 52 men with sickle-cell disease, 20 (38%) reported having a history of priapism [7]. In a recent study, 27 of 98 (28%) reported a history of priapism on direct questioning [8]. This latter study highlighted the poor knowledge and awareness of this complication in both patients and families of those with sickle-cell disease. Furthermore, the major sequelae of priapism, i.e. erectile dysfunction and equally importantly, sexual function, is poorly documented in this group of patients. In addition, the multitude of described treatments available for priapism is also of interest, and include hydration, analgesia, anaesthesia, mild tranquillisers, oestrogens, blood transfusion, sedation, vasodilators, anticoagulants, antimuscarinics, antifibrinolytics, haemoglobin F modifiers and surgical procedures of varying levels of complexity. This reflects a clear lack of consensus on the best treatment of this condition, and in turn reflects the paucity of published and consistent evidence on the efficacy of intervention. We therefore examined some of these issues, from the perspective of the patient and physician, to add to the knowledge available about this often distressing complication of sickle-cell disease.

Patients and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Authors

A short structured questionnaire was developed and given to all males with sickle-cell disease in five centres (three in the UK and two in Nigeria) with a specialist interest in the management of this condition. There were five main questions to elicit the nature, frequency, duration, treatment (including perceived efficacy) and complications associated with priapism. The questionnaire was initially validated with small cohorts of adults and children of differing backgrounds to ensure that the desired information was obtained reliably. A distinction was made between acute (severe) or prolonged priapism (lasting > 24 h) requiring emergency medical attention, and ‘stuttering’, recurrent priapism of a shorter self-limiting duration. Where necessary or requested, patients were assisted by parents and/or a nurse in completing the questionnaire.

A separate questionnaire was developed and given to all UK haematologists with a special interest in sickle-cell anaemia. All the physicians were registered members of the UK Haemoglobinopathy Forum (an academic body whose main focus is research and education in haemoglobinopathies). The questionnaire was designed to elicit information about the relative frequency with which each physician encountered this clinical problem, their preferred first- and second-line treatments, and how effective the physicians thought the interventions were. We also asked what complications of priapism had been encountered and how often (and at what point) specialist urological consultation was obtained.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Authors

In all, 130 patients from the five participating centres completed the questionnaires. In Nigeria, because of difficulties with the postal services, questionnaires were given directly to patients when they attended the outpatient clinic for routine follow-up, resulting is a response rate of 100%. Questionnaires for patients in the UK centres were sent by post (with a stamped addressed envelope enclosed) to all registered male patients; the UK response rate was 22%, giving an overall response rate of 51%. Table 1 shows the demographics and genotypes of the study population; 79% (102 patients) had homozygous sickle-cell anaemia (mean age 25 years, sd 11.0, range 4–66).

Table 1.  Patient demographics and genotypes, acute/prolonged attack and hospital treatment, precipitating events, and self-treatments
 Centre 
Variable12345Total
  1. Centres: 1, Manchester Royal Infirmary; 2, North Middlesex Hospital, London; 3, City Hospital, Birmingham; 4, Lagos University Teaching Hospital, Nigeria; and 5, University College Hospital, Ibadan, Nigeria. *Some respondents reported more than one event/treatment.

No. evaluated377945  38  57256
No. responding111410  38  57130
Response rate, %291722100100  51
Mean (sd) age, years27.7 (4.7)40.5 (12.7)36.8 (14.1)  18.9 (7.7)  24.0 (8.3)  25 (11.0)
Genotype, n (%):
SS  7  5  4  36 (97)  50 (89)102 (83)
SC  1  6  5    1 (3)    6 (11)  19 (15)
Sα−thal  1  1  0    0    0    2
Not known   –   –   –     –     –    7
No. with priapism (%)  5  5  3  10 (26)  23 (41)  46 (36)
Attacks/treatment
Acute/prolonged  1  2  1    7  13  24
Hospital treatment  1  2  0    5  13  21
When sought medical helpAfter failed usual  selftreatmentUnbearable  pain   – after 24 h/at onset  immediate/when  unwell2 days (2) > 3 days  pain (2), severe  attack 
Precipitating events *
Sleep  1  1  0    2    4    8
Sexual arousal/intercourse  2  0  3    1    6  12
Fever  1  1  0    3    4    9
Dehydration  2  1  1    0    2    6
Cold weather  0  0  0    3    4    7
Self treatment *
Drink water  2  2  2    2    9  17
Exercise  3  0  0    3    7  13
Analgesia  1  3  0    5  10  19

Of the 130 patients, 46 (35%) answered yes to the question; ‘Have you ever had a persistent and painful erection?’ There was no significant difference in the incidence of priapism among the UK (13 of 35, 37%) and the Nigerian centres (33 of 94, 35%; Fisher's exact test, P = 0.84). The mean age of the onset of priapism was 15 years; 75% of patients reporting priapism had the first episode before their 20th birthday and 25% before their 10th birthday (Fig. 1). The maximum age at the first episode among the study sample was 30 years. Overall, 37 (82%) had a history of stuttering priapism; the median frequency of occurrence of stuttering priapism was three times/month (range 4/week to 3/year). The median duration of each attack was 1.25 h, with the longest attack being 8 h.

image

Figure 1. The Kaplan-Meier episode-free survival plot.

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Twenty-four (52%) patients had a history of the acute (severe) type of priapism (Table 1); only six in this latter group had no history of stuttering priapism. Of the 37 patients with stuttering priapism, 18 (49%) had an acute episode, compared with only six of the 93 (6%) of those not reporting stuttering priapism (significantly different, chi-square test, P < 0.001), indicating an association between the two forms of priapism.

Sexual activity (arousal or intercourse) was the commonest reported precipitating event, followed closely by fever and sleep (Table 1). A variety of self-treatments were reported to be useful by respondents, but analgesia, hydration and exercise were the most frequent reported to be of benefit (Table 1).

Only 26 of 46 (57%) respondents with priapism had formally sought medical attention for the problem, 21 of whom had an acute attack, indicating that only five of 37 (14%) with stuttering priapism had ever consulted a physician about the problem.

In the 24 respondents having an acute/prolonged attack requiring hospital care, a variety of treatments were used and reported by 15 (Table 1). These treatments (with the perceived efficacy of the treatment in parentheses) were: Centre 1, one exchange blood transfusion (EBT, partial), Centre 2, one EBT (very); centre 4, one ice pack + intravenous fluids and analgesia (very); one catheter (very); one EBT (very); one rehydrate and analgesia (very); and one analgesia (partial); Centre 5, four EBT (three very, one partial), Four shunt (very) and one rehydration (very).

Of 46 respondents with a history of priapism, 34 (85%) provided information about their current erectile function. Ten reported that they could not have or maintain normal erections, indicating a 29% incidence of erectile dysfunction in this subgroup. Of the 28 respondents with stuttering priapism, 21 (75%) had normal erections, compared with only two of five with acute priapism (not statistically significant, Fisher's exact test, P = 0.15). This suggests that stuttering priapism has no significant association with erectile dysfunction, i.e. stuttering priapism per se does not invariably lead to impotence, but caution should be used in arriving at this conclusion, as there were few patients. Half of patients with impotence had undergone operative intervention for acute/prolonged priapism.

Of the 46 patients, 29 (63%) provided information about current satisfaction (or otherwise) with sexual intercourse; 11 (24%) indicated that they could not have intercourse to their satisfaction. Only five of these 11 reported erectile dysfunction, suggesting that there were other reasons for sexual dissatisfaction. Two of these reported that despite normal erectile function, the fear of an attack of priapism mitigated against sexual enjoyment.

There was no statistically significant relationship between the age of onset of priapism and erectile function (median onset 17 and 16 years for those with and without normal erectile function, respectively, Mann-Whitney U-test, P = 0.40). There was also no significant relationship between the age of onset of priapism and sexual ability (median onset 18 and 10 years for those with and without normal sexual ability, respectively, Mann-Whitney U-test, P = 0.11), although those with normal sexual ability tended to have a later age of onset.

Physician survey

Of the 85 haematologists surveyed, 18 questionnaires were returned. The preferred first-line treatment was supportive therapy (analgesia, rehydration) plus EBT in 43%. Only one physician indicated corporeal aspiration as a first-line treatment; four indicated corporeal aspiration as the second-line. There was significant variation in the reported efficacy of first-line interventions, while second-line interventions were reported to be uniformly disappointing. Only seven of the 18 physicians indicted that they would always request urological consultation, with a further two indicating they would seek urological consultation between a half and two-thirds of the time.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Authors

Recent attempts to clarify the exact incidence of priapism in this group of patients have revealed a much higher incidence than previously recognized. Mantadakis et al.[8] found that up to 28% of patients aged 5–20 years will experience priapism. The present survey, which included a wider age group, confirmed similar findings, with 75% of patients experiencing their first episode by the age of 20 years. There was an indication that the incidence stabilised by the third decade of life. The possible bias introduced by the different response rates in the UK and Nigeria is acknowledged, but interestingly the prevalence of priapism was similar in the two groups. The high life-time probability of priapism is significant and provides new insights into the magnitude of the problem among patients with sickle-cell disease.

Stuttering priapism in particular is a problem which hitherto these patients were simply inclined to tolerate. Just over half the patients in the present study had formally sought medical advice about the problem. There is published evidence of the lack of awareness of this complication of sickle-cell disease among patients. Only 7% of patients who had not experienced priapism were aware that priapism was a complication of the disease [8]. The variety of self-help treatments reported indicate how patients have learnt to cope with the problem. From information in the present study, simple advice about analgesia, hydration and exercise can now be offered to patients as self-help strategies to curtail an attack of priapism. Other measures of potential benefit include having a warm bath and voiding [8].

There is conflicting evidence about the relative merits of conservative and surgical management for acute priapism. There is a suggestion that successful surgical intervention is less likely to preserve potency than successful conservative intervention. In a comprehensive review by Hamre et al.[9] the preservation of potency appeared to be more successful with conservative, i.e. non surgical treatment; 48 of 51 patients (94%) treated conservatively maintained erectile potency, contrasting with only 25 of 43 (58%) retaining erectile potency after surgery. The surgical group also had a 20% incidence of severe local complications, including cellulitis, penile and skin necrosis, urethral fistulae and abscess formation. In practice, it is apparent that surgery is often reserved for the most severe and prolonged cases, and it is possible that subsequent erectile dysfunction is related as much to the duration of acute priapism as to the surgical intervention. Early intervention by corporeal aspiration and irrigation with α-adrenergic agonists has recently been shown to be successful, even in an outpatient setting, with no incidence of erectile dysfunction at a median follow-up of 40 months [10]. Prompt institution of supportive medical therapy in a prolonged attack, with adjunctive intervention consisting of corporeal aspiration with or with no intracavernosal injection therapy is apparently beneficial.

Clearly, acute priapism in sickle-cell haemoglobinopathy is a problem for which ‘prevention is better than cure’. Limiting the duration of a stuttering episode, as noted, is important. Attempts to use medical intervention to reduce attacks of stuttering priapism have met with some success. Agents such as hydroxyurea, which induce the bone marrow to increase the production of fetal haemoglobin, have been tried, with anecdotal reports of success [11]. Self-administered treatment regimens of oral and/or intracavernosal injections of etilefrine (an α−adrenergic agonist) have also been reported to have some success [12]. Etilefrine is not available in the UK but is in continental Europe. The avoidance of more extensive surgical intervention (by early intensive therapy) appears to be an important principle of management.

Sexual satisfaction is a complex issue and few studies have commented on this among patients with sickle-cell disease. The patients’ perspective reported in the present study showed that while erectile dysfunction was present in almost half, a further 18% indicated that the fear of priapism was detrimental to sexual satisfaction.

When the physicians’ questionnaires are considered it is clear that there is a need for urological input at an earlier stage. It would seem that both surgeons and physicians have therapeutic alternatives at their disposal, which are potentially complementary. An earlier resort to corporeal aspiration (with or without intracorporal injection of an α-adrenergic agonist), which requires urological expertise, is important.

In conclusion, priapism and its sequelae in sickle-cell disease is a significant problem, with a third of patients experiencing the problem at some point. There is a need for better education of patients and families about this complication. The hypothesis that preventing and curtailing attacks of stuttering priapism in these patients could reduce the incidence (and sequelae) of acute episodes requires further investigation. Finally, there should be a greater collaborative involvement between haematologists and urologists in managing these patients.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Authors

We thank Pfizer Pharmaceuticals, and Mrs Verna Angus-Davies (Sickle Cell Counsellor) and Mrs Achuzia (Sickle Cell Support Group), Manchester Sickle Cell and Thalassaemia Centre.

References

Authors

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Authors

A.B. Adeyoju, FRCS(Urol), Specialist Registrar.

A.B.K. Olujohungbe, MD, MRCP, FRC(Path), Consultant Haematologist.

J. Morris, Medical Statistician.

A. Yardumian, MD, FRCP, FRC(Path), Consultant Haematologist.

D. Bareford, MD, FRC(Path), Consultant Haematologist.

A. Akenova, FWACP, Consultant Haematologist.

O. Akinyanju, MD, FRCP, Consultant Haematologist.

K. Cinkotai, FRC(Path) Associate Specialist in Haematology.

P.H. O’Reilly, FRCS, Consultant Urologist.

Abbreviations
EBT

exchange blood transfusion.