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Priapism and erectile dysfunction in sickle cell disease

Priapism and erectile dysfunction in sickle cell disease
Literature review current through: Jan 2024.
This topic last updated: Jul 21, 2023.

INTRODUCTION — Priapism (penile erection in the absence of sexual activity or desire) is a common complication and cause of morbidity in males with sickle cell disease (SCD), including children, adolescents, and adults. The vast majority of cases are ischemic, in which increased pressure compromises vascular circulation (a type of compartment syndrome). Over time, repeated episodes cause permanent damage and erectile dysfunction (ED).

Priapism is considered a medical emergency in which timely diagnosis and appropriate management are vital to preserving normal function. This is a challenging management area because there are few experts dedicated to managing priapism in SCD and few large trials on which to base practice, and management often involves multiple specialties, including urology, emergency medicine, pediatrics, and hematology.

This topic review discusses our approach to the evaluation and treatment of priapism and ED in boys and men with SCD.

Related subjects, including the use of hydroxyurea and regular blood transfusion, as well as overviews of the other clinical findings and routine management of SCD, are presented separately:

Hydroxyurea – (See "Hydroxyurea use in sickle cell disease".)

Transfusion – (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques".)

Clinical features – (See "Overview of the clinical manifestations of sickle cell disease".)

Routine management (child) – (See "Sickle cell disease in infancy and childhood: Routine health care maintenance and anticipatory guidance".)

Routine management (adult) – (See "Overview of the management and prognosis of sickle cell disease".)

Transition from pediatric to adult care – (See "Sickle cell disease (SCD) in adolescents and young adults (AYA): Transition from pediatric to adult care".)

PATHOPHYSIOLOGY AND CLASSIFICATION

Definitions — Priapism is defined as a persistent penile erection that is not related to sexual interest or desire. It can be categorized as low flow (ischemic) or high flow (nonischemic). Low-flow priapism accounts for the vast majority of cases of priapism in individuals with SCD.

Low-flow/ischemic priapism – Low-flow priapism (also called ischemic or veno-occlusive) is responsible for >95 percent of priapism presentations in SCD [1].

Major episodes – While ischemic priapism can last for any time, the longer the course of the erection, the greater the potential for permanent damage to the penile tissue. Episodes lasting ≥4 hours (commonly referred to as major episodes) are especially concerning because ischemia for this duration is associated with a greater risk of permanent tissue damage.

Beyond 24 hours, there may be tissue necrosis and scarring, leading to erectile dysfunction (ED).

Stuttering priapism – Stuttering priapism (also called recurrent ischemic priapism [RIP]) is characterized by brief, recurrent episodes of transient, self-limited priapism [2]. Each episode typically lasts for a few minutes to up to three hours. Like other forms of ischemic priapism, the episodes are painful and unrelated to sexual interest.

High-flow priapism – High-flow priapism (also called nonischemic or arterial) is a rare form of priapism in which the arterial blood supply to the cavernous tissue is disrupted. This typically occurs with penile trauma, penile arterial aneurysm, or iatrogenic causes (eg, needle injury). Fistula formation between the cavernous artery and the lacunar spaces results in unregulated penile engorgement. High-flow priapism is typically not painful and may resolve spontaneously with minimal complications; emergency interventions often are not needed.

ED is defined as the inability to achieve or sustain an erection firm enough for sexual intercourse. ED is a common complication of priapism in SCD and results from repeated episodes of ischemia-induced tissue damage that interfere with the normal vascular changes that lead to an erection.

Mechanisms of priapism

Normal physiology – The basal, flaccid state of the penis is maintained by the sympathetic nervous system that produces high vascular and smooth muscle tone. Penile erection occurs typically in response to parasympathetic nervous system inputs (eg, genital stimulation or psychosexual excitement). Parasympathetic inputs increase arterial blood flow to the penis via the cavernous and helicine arteries, filling the sinusoids and leading to distension of the trabecular cavernosal tissue (figure 1) [3]. Cavernosal distension restricts venous outflow and permits sustained engorgement [1].

Reflex erections are physiologic erections not due to sexual excitement (eg, during rapid eye movement [REM] sleep) [4]. They can occur in any age (even neonates and young children). Sleep-related erections are also highly androgen-dependent [5]; this explains why anti-androgens may be helpful in some individuals who have frequent priapism episodes upon awakening from sleep. (See 'Hormonal therapies' below.)

Nitric oxide (NO) signaling is one of the principal mediators of erection; it causes smooth muscle relaxation in response to parasympathetic inputs. NO is produced in neuronal and endothelial cells by nitric oxide synthase (NOS), using arginine and oxygen as precursors [4]. NO readily diffuses into smooth muscle cells in the cavernosal artery and the sinusoidal space, where it activates guanylate cyclase, leading to increased cyclic guanosine monophosphate (cGMP). cGMP-dependent protein kinases produce signals that reduce intracellular calcium, leading to smooth muscle relaxation, vasodilation, and increased blood flow into the penis.

The erectile response is terminated when phosphodiesterases (PDEs; especially PDE-5, the target of ED drugs) hydrolyze and inactivate cGMP, leading to smooth muscle contraction.

Low-flow priapism mechanism – Low-flow priapism is associated with decreased or absent blood flow in the penile arteries caused by high pressure in the venous sinuses of the corpora cavernosa, which leads to tense rigidity and pain, a type of compartment syndrome. The majority of patients with SCD and priapism are homozygous for hemoglobin S. However, priapism has been described in patients with hemoglobin SC disease, sickle cell beta thalassemia, and sickle cell trait [6-8].

Many episodes of SCD-associated priapism occur upon awakening from sleep, as REM-sleep erections are common and occur by the same mechanisms. Other precipitating factors are discussed below. (See 'Precipitating factors' below.)

NO signalling – Detumescence does not appear to function normally in some individuals with SCD. This may be because NO signaling also regulates PDE-5 protein expression; when NO is chronically depleted (as in individuals with SCD), PDE-5 levels are lower, and the setpoint for termination of the erection is altered [3,9]. An increased risk of priapism in the setting of a low NO state is counterintuitive since penile erection requires high levels of NO. A plausible biological explanation is that priapism occurs due to PDE-5 dysregulation (uncontrolled signaling).

Evidence linking NO depletion with priapism in SCD includes:

-Mouse models of reduced NO synthesis (double NOS knockout [dNOS-/-]) have priapism, pronounced erectile responses, and reduced PDE-5 signaling [10]. The dNOS-/- recapitulates the SCD priapism mouse models [10,11]. In both dNOS-/- and the SCD mice, treatment with a compound derived from hydroxyurea that acts as an NO donor was able to reverse the priapism phenotype [12]. Adenosine mediates vasodilation and NO synthesis, and mouse models have also suggested a role for elevated levels of adenosine in priapism, although it is not known whether a similar effect occurs in people with SCD [3,13,14].

-Individuals with SCD have decreased circulating NO levels due to chronic hemolysis, which releases free hemoglobin (a prominent NO scavenger) into the circulation [15,16]. Hemolysis also releases the enzyme arginase into the circulation; arginase depletes NO by metabolizing the NO precursor arginine into ornithine. NO may also be decreased by excess superoxide anion, a byproduct of oxidative stress. In a case-control study involving participants in the Cooperative Study of Sickle Cell Disease (CSSCD), individuals with a history of priapism had more clinically severe SCD, including higher rates of stroke, acute chest syndrome, and acute painful episodes, as well as increased laboratory markers of hemolysis such as lower hemoglobin, higher reticulocyte count, higher lactate dehydrogenase (LDH), and higher bilirubin [17]. Reduced NO bioavailability has also been proposed to contribute to pulmonary hypertension in SCD. (See "Pulmonary hypertension associated with sickle cell disease", section on 'Pathogenesis'.)

-PDE-5 levels are low in mouse models of SCD and in individuals with SCD and priapism. The low PDE-5 levels may lead to an altered setpoint for PDE-5 homeostasis. Regular treatment with a PDE-5 inhibitor leads to a steady increase in cGMP, and subsequently the incited cGMP-promoter activity induces tissue expressions of PDE-5 [18]. This may explain the paradoxical effect of chronic administration of PDE-5 inhibitors such as sildenafil in reducing priapism [3]. (See 'PDE-5 inhibitors (sildenafil and tadalafil)' below.)

The physiology of ischemic priapism (and vaso-occlusion generally) in SCD remains an area of active investigation. Mechanical sludging of red blood cells (RBCs) in the penile vasculature, previously thought to be responsible for priapism in SCD, is considered less likely to play a major role. (See "Pathophysiology of sickle cell disease".)

High-flow priapism mechanism – High-flow priapism occurs when the arterial inflow into the penis is increased, often due to trauma or injury to the cavernosal artery that creates a fistula between the artery and lacunar spaces. Tissue ischemia is not a major component of high-flow priapism because venous outflow remains intact. As a result, high-flow priapism typically is not painful and often resolves spontaneously.

Mechanisms of ED — ED results when the normal response to parasympathetic inputs is blunted, preventing normal erections. There are many factors that contribute, as discussed separately. (See "Epidemiology and etiologies of male sexual dysfunction".)

In SCD, a major mechanism of ED is prior ischemic priapism, especially prolonged ischemia (episodes lasting >12 hours) and more frequent episodes of ischemia are likely to increase the risk of ED [6,19-21]. The age at which the episodes occur may also contribute; some series have reported that priapism during childhood is less likely to result in ED than priapism in adulthood [19]. Over time, ischemia leads to cellular injury and inflammation, culminating in irreversible damage and fibrosis in the corpora cavernosa.

Individuals with priapism may fear sexual intercourse because of the risk of precipitating a priapism event [6].

EPIDEMIOLOGY

Prevalence of priapism – The prevalence of priapism is estimated to be approximately 35 to 45 percent in males with SCD [6,19,20,22-24]. The actual prevalence may be higher, as some individuals may be reluctant to mention this symptom or to report it in surveys.

In a cross-sectional study from Nigeria involving 500 males with SCD, 33 percent of adults had a history of priapism [24]. The remainder had major priapism (lasting ≥4 hours). Due to shame, lack of knowledge, and paucity of effective medical treatment to prevent or actively treat priapism, a high proportion never sought medical attention (approximately 50 percent).

In a survey of 104 boys and men from Jamaica who were "not reticent to discuss it," at least one episode of priapism was reported by 44 individuals (42 percent) [19]. In a series from a pediatric urology clinic that included 155 boys with SCD, priapism occurred in 10 (6.5 percent) [25]. The priapism prevalence in children reported in this cohort may be lower than expected because only severe cases are likely to be referred to urology clinic.

Prevalence of ED – Erectile dysfunction (ED) following episodes of priapism is very common in individuals with SCD, with reported prevalences of 20 to 30 percent [6,19]. In our practice, ED affects nearly 40 percent of individuals with SCD who have recurrent ischemic priapism (RIP), even if the episodes are minor [26].

CLINICAL FEATURES AND EVALUATION

Typical presentations — Priapism is a clinical diagnosis made when an unwanted erection is present.

Priapism in SCD may occur at any age, but typically it becomes a more significant clinical problem after puberty. The median age of onset is in adolescence (12 to 15 years), with the first episode occurring before age 20 in 75 to 90 percent of affected individuals [6,19,23].

Rarely, individuals without prior knowledge of their SCD status may present with priapism [21]. In a review of the underlying conditions associated with priapism in children and adolescents, SCD accounted for 65 percent of cases; the remainder were related to trauma, leukemia, or medications [4].

Most individuals do not have a history of trauma; rarely, a history of trauma or surgery on the penis may suggest damage to the cavernosal artery and high-flow, nonischemic priapism. (See 'Pathophysiology and classification' above.)

Ischemic priapism is painful. Often the erection is present upon awakening from sleep [25,27,28]. It typically occurs in the absence of another acute vaso-occlusive illness such as acute chest syndrome. However, other sites of pain may be present, and there may be a history of an acute illness with fever or dehydration. (See 'Precipitating factors' below.)

The duration of the erection is not relevant to diagnosis, but it affects the likelihood of long-term complications and thus has an impact on the urgency and type of interventions needed.

Episodes may present as shorter, more frequent episodes (stuttering priapism) or major episodes (lasting >4 hours). (See 'Definitions' above.)

Individuals with priapism commonly have stuttering priapism (over 70 percent) [6,24]. Stuttering episodes often occur in clusters, approximately two to three times per week for several weeks prior to the abating of symptoms.

In a cohort study of adults with sickle cell anemia, the sum of priapism episodes in three months predicts the occurrence of a major priapism [29]. Also, in patients with a history of at least three episodes of priapism in the past 12 months, there is an 80 percent chance of having another episode within 30 days. Sometimes stuttering priapism is a precursor to a major priapism episode. In a review of 39 patients with priapism who presented for medical care, the mean duration of symptoms was 22 hours (range 6 to 70 hours), with four presenting to the hospital more than 36 hours after the onset of symptoms [21]. In a series from Jamaica, 23 patients had experienced prolonged major episodes of priapism lasting more than 24 hours; of these, 14 (61 percent) were preceded by multiple episodes of stuttering priapism [19].

An ischemic priapism episode lasting at least four hours is a urologic emergency. (See 'Ischemic priapism: Acute management' below.)

The frequency of priapism episodes is also variable. Some individuals have only a single episode, while others have as many as 52 episodes per year (approximately once per week) [20]. In a series from Jamaica, approximately one-third of individuals with priapism had one or two events, and two-thirds reported 10 or more episodes [19].

Precipitating factors — Priapism appears to be more frequent in individuals with other complications of SCD, especially elevated tricuspid regurgitation velocity and leg ulcers [16,30]. However, vaso-occlusion in other sites does not appear to trigger an episode of priapism.

In one series of individuals with SCD, the most common precipitating factors were sexual activity, fever, and/or dehydration [6]. In another series, 54 of 104 individuals reported priapism in association with going to sleep, sleeping (45 individuals), or awakening [19]. Another 10 individuals in this series had episodes immediately after sexual intercourse.

While urination may reduce discomfort, there is no evidence that a full bladder plays a role in priapism. The association of a full bladder with stuttering priapism is likely due to the common occurrence of stuttering priapism upon awakening when the bladder happens to be full. (See 'Mechanisms of priapism' above.)

We have also seen episodes of priapism related to the use of illicit or psychotropic drugs and/or alcohol [31]. A list of drugs precipitating priapism is presented in the appendix of a 2022 publication [29]. In some cases, men may inject illicit drugs such as cocaine directly into the penis. Management is similar regardless of these practices.

Some medications thought to precipitate priapism may not actually do so:

We do not believe that sildenafil alone precipitates priapism; in fact, a regimented sildenafil dose may actually reduce the severity of priapism (see 'Prevention' below). In our experience, priapism in the setting of sildenafil use is likely to have been precipitated by concurrent use of other substances such as cocaine.

In our experience, topical testosterone and testosterone replacement in individuals with testosterone deficiency do not cause priapism. Only the injectable forms of testosterone that produce supraphysiologic levels have been implicated.

A prior history of trauma to the genital area may suggest the presence of "high-flow priapism" with damage to the cavernosal artery.

History, examination, and cavernosal blood gas analysis — The history should determine the duration of the episode, circumstances associated with its onset, hydration status, and use of medications. We specifically ask about erectogenic drugs, psychoactive substances, and recreational drugs. Prior therapies and interventions are also important, including therapies that have been effective for treating priapism as well as surgical interventions or other procedures that may have led to aneurysm formation.

Time-sensitive urologic consultation, typically before the fourth hour of priapism episode, is prudent in all cases to assist with evaluation, cavernosal blood gas analysis (often recommended but seldom done because of high probability of ischemic priapism in SCD), and management. (See 'Ischemic priapism: Acute management' below.)

The examination should focus on medical conditions, especially infections or causes of dehydration. As an example, a lung examination should focus on possible pneumonia, and abdominal examination should assess possible gallbladder disease (eg, right upper quadrant pain).

Priapism does not cause fever. Any fever should be thoroughly evaluated to determine the cause and appropriate antibiotics provided if indicated. (See "Evaluation and management of fever in children and adults with sickle cell disease", section on 'Empiric antibiotic therapy'.)

Examination of the penis should determine the degree of tumescence and signs of trauma [1,32]. Frog-leg position allows optimal visualization of the perineum and scrotum to identify ecchymoses, induration, or other evidence of traumatic injury. The examination is often helpful in distinguishing ischemic from nonischemic priapism.

The principal laboratory test to diagnose ischemic priapism and distinguish it from nonischemic priapism is aspiration of blood from the corpus cavernosum (which contains the venous sinuses) [1,32]. Ischemic priapism is by far the most likely cause of priapism in the absence of injury or trauma.

In ischemic (low-flow) priapism, the penis is erect/rigid and painful with a soft glans. Corporal blood is dark in color. Blood gas analysis shows acidosis, hypoxia, and hypercapnia (typical values: pH <7.25, pO2 <30 mmHg, pCO2 >60 mmHg).

In nonischemic (high-flow) priapism, the penis is more pliable. Corporal blood is bright red in color. Blood gas analysis shows a normal pH (typical values: pH approximately 7.40, pO2 >90 mmHg, pCO2 <40 mmHg).

Laboratory testing and imaging — Individuals with SCD who present with suspected low-flow priapism are evaluated with a complete blood count (CBC) and reticulocyte count that should be compared with the individual's baseline.

Significant hemoglobin decrease (≥2g/dl) below the individual's baseline with hemodynamic-related symptoms (mental status changes, unsteadiness), clinical findings (tachycardia, increased respiratory rate, decreased hemoglobin oxygen saturation), or both, are indications for transfusion. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Indications for transfusion'.)

A white blood cell (WBC) count much higher or lower than the individual's baseline raises the possibility of infection; this is especially concerning because individuals with SCD are functionally asplenic and are at risk for infection with encapsulated organisms.

Individuals with fever and/or a WBC count above their baseline should have blood cultures drawn. (See "Evaluation and management of fever in children and adults with sickle cell disease".)

In selected cases, imaging of penile blood flow using color duplex ultrasonography may be helpful. Examples include:

Individuals for whom corporal blood gas analysis cannot be obtained

History of trauma

Confusing results from corporal blood gas analysis

Initial therapy is ineffective

Those who require serial monitoring after an intervention

Doppler ultrasonography in ischemic priapism shows absent or severely reduced blood flow in the cavernosal arteries. In nonischemic priapism, the flow velocity in cavernosal arteries is typically high, and a fistula or pseudoaneurysm may be present.

We use penile arteriography when planning interventions such as embolization for nonischemic (high-flow) priapism [1]. (See 'Management of high-flow priapism' below and "Priapism", section on 'Nonischemic priapism'.)

ISCHEMIC PRIAPISM: ACUTE MANAGEMENT

Management at home — Most episodes of priapism are brief or stuttering and resolve without medical intervention [23]. Instructions should be provided for home management, including when to seek medical attention.

For stuttering priapism or brief episodes of priapism (eg, <3 hours), patients should be advised to maintain hydration (eg, drink extra fluids) and to use oral analgesics for pain control. Some patients have found that exercise, warm or cold compresses, and masturbation with ejaculation may also be soothing and provide some pain relief [33]. If other interventions have proven effective in the past, these may be used as well. (See 'Prevention' below.)

Selected individuals with SCD who have frequent episodes of major priapism may be taught by a urologist to perform self-intracavernosal injections of an alpha-adrenergic agent such as etilefrine [34,35]. (See 'Aspiration and irrigation of the corpus cavernosum' below.)

If the priapism persists >4 hours, patients should present themselves to an emergency department or specialized SCD center for intravenous hydration, parenteral analgesia, and urologic evaluation. (See 'Management in the emergency department and hospital' below.)

Management in the emergency department and hospital — Prompt recognition and appropriate treatment of an ischemic priapism episode are critical to alleviate pain and to prevent ischemic tissue injury and its complications. Priapism lasting >4 hours is a urologic emergency because it represents a compartment syndrome of the penis; at six hours, irreversible tissue damage can begin to occur.

There are no randomized trials evaluating treatments for detumescence (resolution of an acute priapism event), although several therapies have been tested in small studies [36]. Our approach is based on our clinical experience and available information about the underlying pathophysiology of detumescence [1,32].

Analgesia – Priapism can be extremely painful, and appropriate analgesia should not be withheld while awaiting urologic consultation or the results of imaging studies or laboratory tests. (See "Acute vaso-occlusive pain management in sickle cell disease".)

Aspiration and irrigation – Urologic consultation should be obtained without delay, in episodes that last at least two hours, to assist with the evaluation and management, especially if aspiration of cavernosal blood and irrigation is needed. (See 'Aspiration and irrigation of the corpus cavernosum' below.)

Supportive care – Attention to the medical status of the patient is important, including correction of dehydration (intravenous fluids), correction of any metabolic abnormalities, provision of supplemental oxygen if the patient is hypoxemic, and/or treatment of any infection or other acute medical illness.

No systemic pharmacologic therapies have been demonstrated to have efficacy in treating acute priapism. The principal focus for prolonged episodes is to treat the penis directly. (See 'Aspiration and irrigation of the corpus cavernosum' below.)

There is limited evidence that simple red blood cell (RBC) transfusion is an effective treatment for an acute priapism event, consisting mainly of isolated observations in which cause and effect is unclear, and transfusion usually is not indicated. However, RBC transfusion should not be withheld if other conditions are present for which transfusion is indicated (eg, stroke, acute chest syndrome, or severe anemia with associated symptoms and/or evidence of hemodynamic compromise). (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Indications for transfusion'.)

We reserve RBC apheresis (exchange transfusion) for rare, selected cases of acute priapism that do not improve with other therapies. For prolonged priapism refractory to surgical and pharmacologic interventions, we will use exchange transfusion, with a target hemoglobin S reduction to <30 percent and a total hemoglobin typically no greater than 10.5 g/dL. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Exchange blood transfusion'.)

Reviews of the evidence have concluded that exchange transfusion does not improve time to detumescence or other outcomes [37]. The American Society for Apheresis (ASFA) considers the role of exchange transfusion for priapism as "not established" (category III), and the 2014 National Institutes of Health (NIH) SCD guidelines do not recommend transfusion for acute cases of priapism based on low-quality evidence [38,39]. An association of SCD, priapism, and exchange transfusions followed by neurologic events (ASPEN syndrome) have also been described, although the absolute risk is unknown [40]. Despite these concerns, our collective experience indicates that RBC apheresis may be effective and is worth considering when all other treatments have not been successful. All transfusions carry risks of transfusion reactions, alloimmunization, and infection, as well as other complications related to hyperviscosity. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology", section on 'ASFA therapeutic categories' and "Transfusion in sickle cell disease: Management of complications including iron overload".)

Adults with SCD admitted to the hospital with an acute medical illness, including priapism, should receive venous thromboembolism (VTE) prophylaxis. We do not use VTE prophylaxis in children <18 years of age with SCD unless there are other risk factors (family history of thrombophilia, other comorbidity associated with VTE, history of prior VTE). (See "Overview of the management and prognosis of sickle cell disease", section on 'Thromboembolism prophylaxis'.)

Aspiration and irrigation of the corpus cavernosum — For individuals with ischemic priapism lasting >4 hours, we suggest aspiration of blood from the corpus cavernosum, with or without saline irrigation, followed by injection of an alpha-adrenergic agonist [22]. The goal of this treatment is to cause detumescence and in turn allow oxygenated blood to re-enter the cavernosa.

Our approach is consistent with a 2022 guideline from the American Urological Association (AUA) on the management of priapism [41,42].

Individuals treated with alpha-adrenergic agonist for secondary prevention of priapism should be aware of potential complications including intracerebral hemorrhage and myocardial ischemia [43-45].

The procedure is typically conducted by a urologist or a clinician familiar with the penile anatomy and the details of the procedure.

Conscious sedation can be used along with local anesthesia, especially for children, individuals who have not had the procedure before, or others who have high procedure-related anxiety.

A penile ring block with lidocaine is administered for local pain control using a 25- or 27-gauge needle.

Two needles (19- or 21-gauge) are placed through the glans, one into each corporal body. One needle is for irrigation and the other is for aspiration.

Clot is aspirated if possible. Aspiration may relieve some pressure that is contributing to the lack of blood flow and may be sufficient to cause detumescence in 95 percent of cases (37 of 39) [46]. If detumescence occurs, the injection of an alpha-adrenergic agonist may be omitted.

The initial blood sample may be sent for blood gas determination if this was not done previously or concerns remain regarding whether the priapism is ischemic or nonischemic.

Once low-flow priapism is confirmed, an alpha-adrenergic receptor agonist (alpha-adrenergic agent) is injected. Alpha-adrenergic agonists induce smooth muscle contraction in the penile helicine arteries, causing blood to flow out of the corpora cavernosa. Typically, we use phenylephrine diluted to 100 to 500 mcg/mL and injected in a volume of 0.5 to 1 mL every five minutes for a total of three injections. This procedure, when coupled with aspiration, is sufficient to cause detumescence in the majority of cases.

If priapism does not resolve with the more dilute phenylephrine solution, the injections can be continued for approximately one hour [47]. Alternatively, the remaining phenylephrine is diluted in saline to a final concentration of 10 mcg/mL, and the corporal bodies are irrigated with the diluted phenylephrine/saline mixture. Failure of this therapy to produce detumescence may indicate the need for a surgical shunt procedure. (See 'Surgical management' below.)

We avoid beta-adrenergic agonists and mixed alpha-/beta-adrenergic agents (eg, etilefrine; not available in the United States) in the irrigation solution because beta-adrenergic stimulation can cause smooth muscle relaxation, which increases arterial blood flow into the corpora cavernosa, worsening priapism. Beta-adrenergic agents may cause cardiac complications including arrhythmias and/or acute coronary syndrome [48].

The efficacy of aspiration and irrigation with an alpha-adrenergic agonist has been demonstrated in small case series. A prospective study evaluated outcomes in 15 individuals with SCD who presented to the emergency department with priapism that lasted for ≥4 hours. [46]. There were 39 episodes of priapism among these individuals; one individual had 15 episodes. Aspiration of blood and irrigation with dilute phenylephrine produced immediate detumescence on 37 occasions (95 percent). There were no major short- or long-term adverse events, and none of the individuals required hospitalization.

Aspiration and irrigation may be less successful in prolonged priapism (episodes lasting >72 hours). This may be because the erectile tissue is unable to contract due to severe or prolonged acidosis and hypoxia. Higher doses of phenylephrine have been used for prolonged priapism [49]; however, it is preferable to intervene earlier in the course of the episode. Even if aspiration and irrigation are not done earlier, it is worthwhile to consider using later in the course to relieve pain associated with the ischemic episode.

Aspiration and irrigation can be repeated, although if it fails to result in detumescence after a third attempt, this should prompt consideration of a surgical shunt. (See 'Surgical management' below.)

Surgical management — Surgical management is reserved for individuals with SCD for whom aspiration and injection of an alpha-adrenergic agonist do not result in detumescence in up to two or three attempts. Surgical shunts allow the stagnant blood to drain from the corpora cavernosa and arterial blood flow to be re-established.

We have developed a modified distal penile corpora-glanular shunt procedure (the Burnett snake maneuver, a modification of the open Al-Ghorab shunt) [50]. In our report of 10 patients with priapism due to other causes (ie, not SCD) who were treated with this approach after initial aspiration and irrigation did not produce detumescence, the shunt was effective in eight; the remaining two required a penile prosthesis [31]. Complications included a wound infection with skin necrosis in one and intraoperative urethral injury in another.

If distal shunt procedures are ineffective, a penile prosthesis may be used. Case reports suggest that epidural analgesia may also be used as a component of treatment for priapism in children [51,52]. The 2022 AUA/Sexual Medicine Society of North America (SMSNA) guidelines suggest that proximal shunts are mainly of historical interest [41,42]. Additional information on the surgical management of priapism is presented separately. (See "Priapism", section on 'Surgical therapy'.)

While erectile dysfunction (ED) is cited as a complication of surgical shunt procedures, individuals with SCD who undergo these procedures have already had at least one major, prolonged episode of priapism with prolonged tissue ischemia, which undoubtedly contributes to ED. (See 'Mechanisms of ED' above.)

PREVENTION

Overview of prevention — Education and discussions about priapism should be included in the routine health evaluations of boys and men with SCD, and instructions should be provided regarding how to manage episodes at home and when to seek medical attention.

Many individuals are not comfortable initiating discussions about sexual health with members of their care team, and even those who do may infer that this information is not important to the clinician if it is not included in discussions about vaso-occlusive complications [33]. Others may not know that priapism is a complication of SCD, or they may not be aware of the consequences of a prolonged priapism episode [21]. (See "Overview of the management and prognosis of sickle cell disease", section on 'Routine evaluations and treatments' and "Sickle cell disease in infancy and childhood: Routine health care maintenance and anticipatory guidance", section on 'Priapism'.)

As with all individuals who present with vaso-occlusive pain, attention to general health and avoidance of precipitating factors such as infection or dehydration is important. This may be worth emphasizing with certain individuals who appear to have a strong correlation between priapism events and certain precipitating factors (see 'Precipitating factors' above); however, many episodes occur during sleep or with sexual activity.

Certain medications that block alpha-adrenergic receptors (eg, phenothiazines such as cyamemazine, alpha-adrenergic antagonist antihypertensive agents) may precipitate priapism [53]. This association, as well as the possible association between priapism and underlying anxiety disorders, may be a consideration in primary or secondary prevention [54].

For individuals with acute priapism, we avoid medications that may exacerbate priapism, including vaso-active erectile agents (papaverine, phentolamine, prostaglandin E1), certain antihypertensive agents (prazosin, terazosin, tamsulosin, hydralazine, guanethidine, propranolol), and certain anxiolytic, antidepressant, and antipsychotic medications (eg, hydroxyzine, trazadone, bupropion, fluoxetine, sertraline, lithium, clozapine, risperidone, olanzapine, chlorpromazine, thioridazine, phenothiazines).

For individuals with repeated episodes of major priapism or stuttering priapism, secondary prevention strategies should be addressed. Previous episodes of major priapism and stuttering priapism both are associated with an increased risk of major priapism episodes in the future [19]. Our approach is as follows:

Hydroxyurea – We suggest hydroxyurea if the patient is not already taking the medication. We favor increasing to the maximum tolerated dose only when there is laboratory evidence of adherence (typically an increase in mean corpuscular volume [MCV], decrease in white blood cell [WBC] count, and increase in hemoglobin F levels and total hemoglobin when compared with baseline levels). (See 'Hydroxyurea' below.)

Sildenafil, self-injection, prosthesis – For continued episodes despite hydroxyurea, one option is daily sildenafil (see 'PDE-5 inhibitors (sildenafil and tadalafil)' below). This is used to reset the PDE-5 regulatory circuit (see 'Mechanisms of priapism' above) rather than as an erectogenic drug. Other options include regular use of alpha-adrenergic agonists by self-injection into the penis, which the individual usually learns how to perform, penile prosthesis, regular blood transfusions, or a hormonal therapy. These approaches are very different in their associated burdens and risks, and the decision is highly patient-dependent. (See 'Alpha- and beta-adrenergic agonists' below and 'Regular red blood cell transfusions' below and "Surgical treatment of erectile dysfunction".)

Medical therapies to prevent recurrent priapism were reviewed in a 2020 Cochrane review that identified only three small randomized trials, which evaluated stilbestrol, sildenafil, etilefrine, or ephedrine [55]. Of these, none showed a statistically significant reduction in the frequency of stuttering priapism or major priapism events. However, these trials were all small, and the evidence was considered insufficient to allow firm conclusions. We sometimes use these agents, as discussed below.

Hydroxyurea — For individuals with frequent or prolonged episodes of priapism who are not receiving hydroxyurea based on other SCD indications, we suggest hydroxyurea. Examples of appropriate settings for this approach include the following:

More than two to three episodes of major priapism per year (lasting for >3 to 4 hours)

Frequent episodes of stuttering priapism (eg, more than once per week or once every other week)

Escalating pattern of symptoms

When hydroxyurea is used, we typically start at a low dose (15 to 20 mg/kg daily) and gradually increase to the maximum tolerated dose based on complete blood count (CBC) parameters. Dosing, monitoring, and adverse effects of hydroxyurea, as well as reproductive considerations, are discussed separately. (See "Hydroxyurea use in sickle cell disease".)

No randomized trials have evaluated prevention of a first episode of priapism; the original trials that demonstrated a benefit of hydroxyurea in SCD did not assess priapism as an endpoint. Limited observational data suggest that hydroxyurea may reduce the likelihood of priapism in patients with SCD [56-58]. Indirect evidence comes from randomized trials and observational studies demonstrating that hydroxyurea reduces many other vaso-occlusive complications. (See "Hydroxyurea use in sickle cell disease", section on 'Evidence for efficacy'.)

Examples of observational evidence for the efficacy of hydroxyurea in secondary prevention of priapism include:

In a series of five individuals with stuttering priapism or major priapism episodes who were treated with hydroxyurea for secondary prevention, four had resolution of priapism [57]. Two individuals who subsequently stopped hydroxyurea had recurrence of priapism that again remitted upon reintroduction of hydroxyurea.

A case report described a 25-year-old male with SCD who had stuttering and acute priapism episodes that resolved with hydroxyurea [58].

Among approximately 200 individuals with SCD enrolled in a clinical trial testing anti-P selectin therapy, nearly two-thirds were receiving hydroxyurea at baseline, and the rate of priapism (median rate, zero episodes per year) was much lower than would be expected based on historical data [56].

However, these studies are difficult to evaluate because soliciting a history of priapism is not uniform among hematologists, and patients' memories may be variable. In our practice, we have some individuals who have priapism despite receiving hydroxyurea with evidence of adequate dosing.

Regular red blood cell transfusions — For individuals who have priapism despite hydroxyurea, it may be appropriate to give a course of chronic (regular) blood transfusions. This assumes that hydroxyurea is being taken as directed and dosed to maximum tolerated dose. (See "Hydroxyurea use in sickle cell disease", section on 'Administration and dosing'.)

If chronic transfusions are used, they are administered similarly to chronic transfusions for other indications, with a goal of maintaining the hemoglobin S (Hb S) <50 percent. This Hb S percentage is slightly higher (ie, less aggressive transfusion) compared with the target of <30 percent used for other, more life-threatening complications. Individuals using this approach should be aware that it is not based on high-quality evidence from randomized trials and that complications of transfusion are possible in the short term (transfusion reactions, alloimmunization) and the long term (iron overload). When we use this approach, we generally re-evaluate the decision after 6 to 12 months. If priapism has not been significantly reduced, we do not continue the therapy indefinitely. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Prophylactic (regularly scheduled) transfusion'.)

In contrast with secondary prevention, blood transfusion is not used routinely to treat an acute episode of priapism. (See 'Ischemic priapism: Acute management' above.)

Other medical therapies for SCD — There are limited data to describe the efficacy of the newer US Food and Drug Administration (FDA)-approved drugs for SCD such as L-glutamine, voxelotor, and crizanlizumab. Clinical trials that led to approval of these drugs did not report data on priapism outcomes, presumably because priapism events were rare.

A phase 2 study of the effect of crizanlizumab on priapism is ongoing (NCT 03938454). In an unpublished report from this study involving 24 patients treated with crizanlizumab for 26 weeks, 17 (71 percent) had a decrease in priapic events [59]. The median reduction in events was 53 percent, with greater benefit in individuals who had more frequent events at baseline.

PDE-5 inhibitors (sildenafil and tadalafil) — The phosphodiesterase (PDE)-5 inhibitors sildenafil and tadalafil are options for people who continue to have episodes of priapism despite hydroxyurea. PDE-5 inhibitor therapy for priapism treatment follows a regimented daily dosing protocol, in distinction from use for erectogenic purposes.

Sildenafil and tadalafil are available in generic form, and patients in the United States may be able to reduce the cost significantly by using coupons.

Additional study of PDE-5 inhibitors is warranted. A phase 2 randomized trial comparing tadalafil and placebo is underway [60]. Available evidence supporting the use of PDE-5 inhibitors includes:

A retrospective chart review study identified 216 individuals with priapism from all causes; 114 had recurrent priapism, 42 were treated with sildenafil, and of these 24 (12 with SCD) could be evaluated for efficacy [61]. Improvement in symptoms was reported in 22 (92 percent) and complete resolution was reported in nine (38 percent). Monthly visits to the emergency department also decreased.

A trial that randomly assigned 13 individuals with SCD (ages 14 to 45 years) who had at least two episodes of priapism per week to receive the PDE-5 inhibitor sildenafil or placebo for eight weeks, followed by an open-label phase in which sildenafil was offered to all of the participants, found no statistically significant differences in the frequency or duration of priapism episodes [62]. However, there was a reduction in episodes in the majority of individuals during the open-label phase. Of the 10 hospital visits for priapism during the study, eight occurred in patients taking placebo or with nonadherence to sildenafil. Nonadherence and low trial accrual were due to fears of the possibility of sildenafil worsening rather than treating priapism.

The mechanism of action of PDE-5 inhibitors is consistent with a role in prevention of priapism (reprogramming PDE-5 and nitric oxide [NO] signaling) [63]. (See 'Mechanisms of priapism' above.)

Alpha- and beta-adrenergic agonists — These agents are another potential option for people who continue to have episodes of priapism despite hydroxyurea.

A potential role for alpha-adrenergic receptor agonists in prevention comes from the known mechanism of detumescence and the observation that an alpha-adrenergic receptor agonist is effective in treating acute priapism episodes when injected into the penis. (See 'Aspiration and irrigation of the corpus cavernosum' above.)

Small studies have suggested that chronic administration of an oral alpha-adrenergic agonist or a combined alpha- and beta-adrenergic agonist may be effective. As an example, etilefrine 50 to 100 mg daily was associated with a good clinical response in 13 of 18 men (72 percent) with recurrent priapism [7]. Therapy with alpha- and beta-adrenergic agonists was evaluated in a trial that randomly assigned 131 individuals with SCD-associated stuttering priapism to receive one of four treatments every night for six months: ephedrine 15 mg, ephedrine 30 mg, etilefrine 50 mg, or placebo [33]. Only 46 individuals completed the six months of treatment; 85 (65 percent) were lost to follow-up despite persistent efforts to contact them. The 46 participants who completed the trial were evenly distributed among the four arms, and there were no statistically significant differences in the number of priapism episodes in any of the arms. There were no major adverse events, although individuals receiving etilefrine reported more palpitations and tachycardia. We believe that additional study of alpha-adrenergic agonists is indicated.

For individuals who wish to try an oral alpha-adrenergic agonist, a reasonable daily dose is 30 to 60 mg of pseudoephedrine at bedtime, plus an additional dose of 30 mg when priapism occurs.

For those who wish to try penile self-injections, this is taught to the patient by the urologist and performed at home when an episode of priapism occurs. (See 'Management at home' above.)

Hormonal therapies — The following hormonal therapies have been used in individuals with priapism:

Anti-androgens – Anti-androgens are used with stuttering priapism, especially episodes that occur on awakening from sleep, because these episodes are highly androgen-dependent (see 'Mechanisms of priapism' above). Case reports have described successful and unsuccessful treatment of SCD-associated priapism with the anti-androgen bicalutamide [64,65].

We generally avoid anti-androgens in peripubertal boys, adolescents, and young men because they are associated with numerous adverse events related to loss of androgen function including impaired growth, decreased bone density, sexual dysfunction, vasomotor symptoms, and changes in body habitus (gynecomastia, decreased penile and testicular size, thinning hair) (see "Side effects of androgen deprivation therapy"). However, this approach may be effective in selected individuals.

Finasteride – Finasteride (a 5-alpha reductase inhibitor) blocks conversion of testosterone to dihydrotestosterone. In a prospective study in which finasteride was administered to 35 individuals with SCD and recurrent priapism, the frequency of episodes was decreased [66]. The initial dose was 5 mg daily, and this was reduced to 3 mg daily after 40 days and to 1 mg daily after 80 days. The only adverse effect was painless gynecomastia in six individuals. However, this agent is known to be associated with decreased libido and erectile dysfunction (ED) in some settings, and additional data are required.

Estrogens – Data on estrogens are very limited, and their use is generally avoided due to the increased risk of thromboembolic complications. A trial randomly assigned 11 individuals with SCD-associated priapism to receive diethylstilbestrol (DES) 5 mg daily or placebo did not find a reduction in priapism, but four individuals initially assigned to take DES had actually not taken it [27]. When these individuals did take the assigned therapy, and when the individuals assigned to receive placebo underwent crossover to DES, nine individuals appeared to have a response at full-dose or lower doses of DES. We consider estrogen investigational and would not use it outside of a clinical trial.

Leuprolide – The gonadotropin-releasing hormone (GNRH) agonist leuprolide was successfully used in an 18-year-old man with SCD; however, no further studies have validated the findings of this report [67].

Ketoconazole – Ketoconazole has anti-androgenic properties and has been used by some clinicians. An example of dosing is to combine ketoconazole 200 mg orally twice daily with prednisone, 5 mg orally four times daily, titrated to reduce the serum testosterone level to approximately 200 ng/dL or improvement of symptoms, whichever came first (final ketoconazole dose range, 100 to 400 mg orally twice daily) [68].

EVALUATION AND MANAGEMENT OF ERECTILE DYSFUNCTION — The best approach to preventing erectile dysfunction (ED) is to treat episodes of acute priapism rapidly and, for those with more than one or two episodes, to evaluate possible use of preventive therapies to reduce their frequency, as discussed above. (See 'Ischemic priapism: Acute management' above and 'Prevention' above.)

Although most cases of ED in individuals with SCD are due to a history of major priapism episodes, it is worthwhile to evaluate and optimize the individual's cardiovascular and neurologic status for possible contributing factors. (See "Evaluation of male sexual dysfunction", section on 'Evaluation for cardiovascular disease' and "Epidemiology and etiologies of male sexual dysfunction", section on 'Erectile dysfunction (ED)'.)

It is also important to enquire about psychologic factors that may be contributing (eg, fear that sexual activity will cause an episode of priapism). (See "Evaluation of male sexual dysfunction", section on 'History'.)

Once these other factors are addressed, management of ED is similar to that in individuals without SCD and may include the use of erectogenic drugs, a vacuum pump, or a penile prosthesis. We are cautious about penile injections of vasoactive inducers of erection due to the possibility of precipitating priapism, but these drugs may be effective for some individuals. Sometimes there is significant scarring of the penile tissue and a prosthesis is the only effective option. (See "Surgical treatment of erectile dysfunction".)

MANAGEMENT OF HIGH-FLOW PRIAPISM — Treatment of high-flow (nonischemic) priapism in individuals with SCD is similar to individuals without SCD and is discussed separately. (See "Priapism", section on 'Nonischemic priapism'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sickle cell disease and thalassemias" and "Society guideline links: Male sexual dysfunction".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Priapism (The Basics)")

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SUMMARY AND RECOMMENDATIONS

Definition and pathophysiology – Priapism is defined as persistent penile erection not related to sexual interest or desire. It can be low-flow (ischemic, vaso-occlusive) or high-flow (nonischemic). Some series estimate priapism affects 35 to 45 percent of men with sickle cell disease (SCD). Ischemic episodes lasting ≥4 hours (major episodes) are especially concerning due to the greater risk of permanent tissue damage from what is essentially a compartment syndrome of the penis. (See 'Pathophysiology and classification' above and 'Epidemiology' above.)

Evaluation – Ischemic priapism is a type of painful compartment syndrome. The history should determine the duration, circumstances associated with its onset, hydration status, medications, and recreational drugs. The examination focuses on infections or causes of dehydration. Examination of the penis should determine the degree of tumescence and signs of trauma. In ischemic priapism, the penis is rigid and painful with a soft glans. (See 'Clinical features and evaluation' above.)

Laboratory testing and role of imaging – A complete blood count (CBC) and reticulocyte count should be obtained and compared with the individual's baseline. Individuals with fever or a white blood cell (WBC) count above their baseline should have blood cultures. In selected cases (confusing results from corporal blood gas, trauma), imaging of penile blood flow using color duplex ultrasonography may be helpful. (See 'Laboratory testing and imaging' above.)

Treatment – For stuttering priapism or episodes lasting <4 hours, patients should be advised to maintain hydration and use oral analgesics, along with other maneuvers that have been helpful in previous episodes. For priapism lasting >4 hours that does not respond to conservative management, we suggest aspiration of blood from the corpus cavernosum, with or without saline irrigation, followed by injection of an alpha-adrenergic agonist (Grade 2C). (See 'Aspiration and irrigation of the corpus cavernosum' above.)

If the aspiration and irrigation do not result in detumescence within a reasonable period of time, a surgical shunt may be required. (See 'Surgical management' above.)

Prevention and counseling – Education about priapism should be included in the routine health evaluations of boys and men with SCD. The best way to prevent erectile dysfunction (ED) in SCD is to treat episodes of priapism rapidly and use appropriate interventions to reduce their frequency. For individuals with frequent major episodes of priapism or other concerning features (eg, escalating stuttering priapism), we suggest hydroxyurea (Grade 2C). Other options may include regular red blood cell (RBC) transfusions, regimented daily use of a phosphodiesterase (PDE)-5 inhibitor such as sildenafil or tadalafil, an alpha-adrenergic agonist (pseudoephedrine), or hormonal therapy. Repeated episodes of priapism may cause such scar tissue that surgical treatment with a penile prosthesis is the best option. (See 'Prevention' above and 'Evaluation and management of erectile dysfunction' above and "Hydroxyurea use in sickle cell disease".)

ACKNOWLEDGMENTS — UpToDate gratefully acknowledges Stanley L Schrier, MD (deceased), who contributed as Section Editor on earlier versions of this topic review and was a founding Editor-in-Chief for UpToDate in Hematology.

The UpToDate editorial staff also acknowledges extensive contributions of Joshua J Field, MD, Donald H Mahoney, Jr, MD, and Vijaya M Vemulakonda, MD, JD, who contributed to earlier versions of this topic review.

  1. Anele UA, Le BV, Resar LM, Burnett AL. How I treat priapism. Blood 2015; 125:3551.
  2. Morrison BF, Burnett AL. Stuttering priapism: insights into pathogenesis and management. Curr Urol Rep 2012; 13:268.
  3. Bivalacqua TJ, Musicki B, Kutlu O, Burnett AL. New insights into the pathophysiology of sickle cell disease-associated priapism. J Sex Med 2012; 9:79.
  4. Donaldson JF, Rees RW, Steinbrecher HA. Priapism in children: a comprehensive review and clinical guideline. J Pediatr Urol 2014; 10:11.
  5. Montorsi F, Oettel M. Testosterone and sleep-related erections: an overview*. J Sex Med 2005; 2:771.
  6. Adeyoju AB, Olujohungbe AB, Morris J, et al. Priapism in sickle-cell disease; incidence, risk factors and complications - an international multicentre study. BJU Int 2002; 90:898.
  7. Okpala I, Westerdale N, Jegede T, Cheung B. Etilefrine for the prevention of priapism in adult sickle cell disease. Br J Haematol 2002; 118:918.
  8. Birnbaum BF, Pinzone JJ. Sickle cell trait and priapism: a case report and review of the literature. Cases J 2008; 1:429.
  9. Kato GJ. Priapism in sickle-cell disease: a hematologist's perspective. J Sex Med 2012; 9:70.
  10. Champion HC, Bivalacqua TJ, Takimoto E, et al. Phosphodiesterase-5A dysregulation in penile erectile tissue is a mechanism of priapism. Proc Natl Acad Sci U S A 2005; 102:1661.
  11. Claudino MA, Franco-Penteado CF, Corat MA, et al. Increased cavernosal relaxations in sickle cell mice priapism are associated with alterations in the NO-cGMP signaling pathway. J Sex Med 2009; 6:2187.
  12. Silva FH, Karakus S, Musicki B, et al. Beneficial Effect of the Nitric Oxide Donor Compound 3-(1,3-Dioxoisoindolin-2-yl)Benzyl Nitrate on Dysregulated Phosphodiesterase 5, NADPH Oxidase, and Nitrosative Stress in the Sickle Cell Mouse Penis: Implication for Priapism Treatment. J Pharmacol Exp Ther 2016; 359:230.
  13. Mi T, Abbasi S, Zhang H, et al. Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling. J Clin Invest 2008; 118:1491.
  14. Wen J, Jiang X, Dai Y, et al. Adenosine deaminase enzyme therapy prevents and reverses the heightened cavernosal relaxation in priapism. J Sex Med 2010; 7:3011.
  15. Kato GJ, Hebbel RP, Steinberg MH, Gladwin MT. Vasculopathy in sickle cell disease: Biology, pathophysiology, genetics, translational medicine, and new research directions. Am J Hematol 2009; 84:618.
  16. Kato GJ, Gladwin MT, Steinberg MH. Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes. Blood Rev 2007; 21:37.
  17. Nolan VG, Wyszynski DF, Farrer LA, Steinberg MH. Hemolysis-associated priapism in sickle cell disease. Blood 2005; 106:3264.
  18. Lin CS. Tissue expression, distribution, and regulation of PDE5. Int J Impot Res 2004; 16 Suppl 1:S8.
  19. Emond AM, Holman R, Hayes RJ, Serjeant GR. Priapism and impotence in homozygous sickle cell disease. Arch Intern Med 1980; 140:1434.
  20. Fowler JE Jr, Koshy M, Strub M, Chinn SK. Priapism associated with the sickle cell hemoglobinopathies: prevalence, natural history and sequelae. J Urol 1991; 145:65.
  21. Bennett N, Mulhall J. Sickle cell disease status and outcomes of African-American men presenting with priapism. J Sex Med 2008; 5:1244.
  22. Rogers ZR. Priapism in sickle cell disease. Hematol Oncol Clin North Am 2005; 19:917.
  23. Mantadakis E, Cavender JD, Rogers ZR, et al. Prevalence of priapism in children and adolescents with sickle cell anemia. J Pediatr Hematol Oncol 1999; 21:518.
  24. Idris IM, Abba A, Galadanci JA, et al. Men with sickle cell disease experience greater sexual dysfunction when compared with men without sickle cell disease. Blood Adv 2020; 4:3277.
  25. Tarry WF, Duckett JW Jr, Snyder HM 3rd. Urological complications of sickle cell disease in a pediatric population. J Urol 1987; 138:592.
  26. Anele UA, Burnett AL. Erectile dysfunction after sickle cell disease-associated recurrent ischemic priapism: profile and risk factors. J Sex Med 2015; 12:713.
  27. Serjeant GR, de Ceulaer K, Maude GH. Stilboestrol and stuttering priapism in homozygous sickle-cell disease. Lancet 1985; 2:1274.
  28. Embury SH, Hebble RP, Mohandas N, Steinberg MH. Sickle Cell Disease: Basic Principles and Clinical Practice, Raven Press, New York 1994.
  29. Idris IM, Abba A, Galadanci JA, et al. Incidence and predictors of priapism events in sickle cell anemia: a diary-based analysis. Blood Adv 2022; 6:5676.
  30. Kato GJ, McGowan V, Machado RF, et al. Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. Blood 2006; 107:2279.
  31. Segal RL, Readal N, Pierorazio PM, et al. Corporal Burnett "Snake" surgical maneuver for the treatment of ischemic priapism: long-term followup. J Urol 2013; 189:1025.
  32. Olujohungbe A, Burnett AL. How I manage priapism due to sickle cell disease. Br J Haematol 2013; 160:754.
  33. Olujohungbe AB, Adeyoju A, Yardumian A, et al. A prospective diary study of stuttering priapism in adolescents and young men with sickle cell anemia: report of an international randomized control trial--the priapism in sickle cell study. J Androl 2011; 32:375.
  34. Virag R, Bachir D, Lee K, Galacteros F. Preventive treatment of priapism in sickle cell disease with oral and self-administered intracavernous injection of etilefrine. Urology 1996; 47:777.
  35. Teloken C, Ribeiro EP, Chammas M Jr, et al. Intracavernosal etilefrine self-injection therapy for recurrent priapism: one decade of follow-up. Urology 2005; 65:1002.
  36. Chinegwundoh FI, Smith S, Anie KA. Treatments for priapism in boys and men with sickle cell disease. Cochrane Database Syst Rev 2017; 9:CD004198.
  37. Merritt AL, Haiman C, Henderson SO. Myth: blood transfusion is effective for sickle cell anemia-associated priapism. CJEM 2006; 8:119.
  38. Schwartz J, Padmanabhan A, Aqui N, et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Seventh Special Issue. J Clin Apher 2016; 31:149.
  39. Yawn BP, Buchanan GR, Afenyi-Annan AN, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA 2014; 312:1033.
  40. Siegel JF, Rich MA, Brock WA. Association of sickle cell disease, priapism, exchange transfusion and neurological events: ASPEN syndrome. J Urol 1993; 150:1480.
  41. Bivalacqua TJ, Allen BK, Brock GB, et al. The Diagnosis and Management of Recurrent Ischemic Priapism, Priapism in Sickle Cell Patients, and Non-Ischemic Priapism: An AUA/SMSNA Guideline. J Urol 2022; 208:43.
  42. Fantus RJ, Brannigan RE, Davis AM. Diagnosis and Management of Priapism. JAMA 2023; 330:559.
  43. Davila HH, Parker J, Webster JC, et al. Subarachnoid hemorrhage as complication of phenylephrine injection for the treatment of ischemic priapism in a sickle cell disease patient. J Sex Med 2008; 5:1025.
  44. Tark BE, Messe SR, Balucani C, Levine SR. Intracerebral hemorrhage associated with oral phenylephrine use: a case report and review of the literature. J Stroke Cerebrovasc Dis 2014; 23:2296.
  45. Constantine ST, Gopalsami A, Helland G. Recurrent Priapism Gone Wrong: ST-Elevation Myocardial Infarction and Cardiogenic Shock After Penile Corporal Phenylephrine Irrigation. J Emerg Med 2017; 52:859.
  46. Mantadakis E, Ewalt DH, Cavender JD, et al. Outpatient penile aspiration and epinephrine irrigation for young patients with sickle cell anemia and prolonged priapism. Blood 2000; 95:78.
  47. http://www.auanet.org/guidelines/priapism-(2003-reviewed-and-validity-confirmed-2010) (Accessed on October 09, 2017).
  48. Lee M, Cannon B, Sharifi R. Chart for preparation of dilutions of alpha-adrenergic agonists for intracavernous use in treatment of priapism. J Urol 1995; 153:1182.
  49. Munarriz R, Wen CC, McAuley I, et al. Management of ischemic priapism with high-dose intracavernosal phenylephrine: from bench to bedside. J Sex Med 2006; 3:918.
  50. Burnett AL, Pierorazio PM. Corporal "snake" maneuver: corporoglanular shunt surgical modification for ischemic priapism. J Sex Med 2009; 6:1171.
  51. McHardy P, McDonnell C, Lorenzo AJ, et al. Management of priapism in a child with sickle cell anemia; successful outcome using epidural analgesia. Can J Anaesth 2007; 54:642.
  52. Labat F, Dubousset AM, Baujard C, et al. Epidural analgesia in a child with sickle cell disease complicated by acute abdominal pain and priapism. Br J Anaesth 2001; 87:935.
  53. Quint R, Lillo-Le Louet A, Pouchot J, Arlet JB. Priapism in sickle cell disease: Beware of neuroleptics. Am J Hematol 2018.
  54. Burnett AL. Anxiety disorders in patients with idiopathic priapism: risk factor and pathophysiologic link? J Sex Med 2009; 6:1712.
  55. Chinegwundoh FI, Smith S, Anie KA. Treatments for priapism in boys and men with sickle cell disease. Cochrane Database Syst Rev 2020; 4:CD004198.
  56. Ataga KI, Kutlar A, Kanter J, et al. Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease. N Engl J Med 2017; 376:429.
  57. Saad ST, Lajolo C, Gilli S, et al. Follow-up of sickle cell disease patients with priapism treated by hydroxyurea. Am J Hematol 2004; 77:45.
  58. Al Jam'a AH, Al Dabbous IA. Hydroxyurea in the treatment of sickle cell associated priapism. J Urol 1998; 159:1642.
  59. Anderson A, El Rassi F, DeBaun MR, et al. Interim analysis of a phase 2 trial to assess the efficacy and safety of crizanlizumab in sickle cell disease patients with priapism (SPARTAN). Blood 2022; 140 (Supplement 1):1636.
  60. Idris IM, Yusuf AA, Ismail II, et al. Rationale and design of a randomized controlled double-blind internal pilot trial for prevention of recurrent ischemic priapism in men with sickle cell disease (PIN Trial). Blood 2022; Supplement 1:5450.
  61. Hou LT, Burnett AL. Regimented Phosphodiesterase Type 5 Inhibitor Use Reduces Emergency Department Visits for Recurrent Ischemic Priapism. J Urol 2021; 205:545.
  62. Burnett AL, Anele UA, Trueheart IN, et al. Randomized controlled trial of sildenafil for preventing recurrent ischemic priapism in sickle cell disease. Am J Med 2014; 127:664.
  63. Burnett AL, Bivalacqua TJ, Champion HC, Musicki B. Feasibility of the use of phosphodiesterase type 5 inhibitors in a pharmacologic prevention program for recurrent priapism. J Sex Med 2006; 3:1077.
  64. Dahm P, Rao DS, Donatucci CF. Antiandrogens in the treatment of priapism. Urology 2002; 59:138.
  65. Molina Escudero R, Rodriguez Fernandez E, Lledo Garcia E, et al. Stuttering priapism: case report and bibliographic review. Arch Esp Urol 2010; 63:559.
  66. Rachid-Filho D, Cavalcanti AG, Favorito LA, et al. Treatment of recurrent priapism in sickle cell anemia with finasteride: a new approach. Urology 2009; 74:1054.
  67. Levine LA, Guss SP. Gonadotropin-releasing hormone analogues in the treatment of sickle cell anemia-associated priapism. J Urol 1993; 150:475.
  68. Abern MR, Levine LA. Ketoconazole and prednisone to prevent recurrent ischemic priapism. J Urol 2009; 182:1401.
Topic 7143 Version 37.0

References

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