Flexible Ureteroscopy in Children with von Willebrand Disease

Abstract

Background and Purpose:

Treatment options for urolithiasis include shockwave lithotripsy (SWL), percutaneous nephrostolithotomy (PCNL), and ureteroscopy. While these treatment options are becoming the standard of care in the pediatric population, children with a bleeding dyscrasia must be approached differently. We report our flexible ureteroscopic experience in children with von Willebrand disease (vWd).

Patients and Methods:

A review of a prospectively maintained database of stone patients was performed. Children with a bleeding diathesis were identified. Stone burden, operative access, intraoperative complications, postoperative complications, stone-free status, and perioperative medical management were evaluated.

Results:

During a 7-year period, a total of five children with a bleeding disorder underwent 7 ureteroscopic and 10 cystoscopic procedures for urinary calculi. The mean patient age was 72.4 months (range 49–123 mos) at the time of the procedure. There were three boys and two girls. Mean follow-up was 29.7 months (range 8–79 mos). Mean stone burden was 6.1 mm (range 3–14 mm) with an average of 1.3 stones per patient. Four patients were known to have vWd before surgical intervention and were pretreated with desmopressin acetate. The remaining patient was found to have vWd based on significant bleeding after ureteral stent placement. No ureters were actively dilated. Flexible ureteroscopy was performed in all cases regardless of stone location. Stone clearance was 100% (7/7). Complications occurred in 6% of procedures (1/17).

Conclusions:

Ureteroscopy is a safe and efficacious modality in the management of urolithiasis in children with a bleeding abnormality. Perioperative medical management of the bleeding diathesis may help reduce complications.

Introduction

T he surgical management of urolithiasis has undergone a dramatic shift over the past 30 to 40 years. Therapy historically consisted of open surgical procedures and lengthy hospital stays.¹ This has now largely been replaced by minimally invasive procedures that are performed on an outpatient basis with similar efficacy and less morbidity.^2

–5 Included in these treatment options are shockwave lithotripsy (SWL), percutaneous nephrostolithotomy (PCNL), and ureteroscopic treatment of stones. Over the last 20 years, advances in technology and the emergence of smaller and more versatile endoscopes have enabled endourologists to apply their skills to the management of pediatric stone disease.^4

–8 These techniques have been demonstrated to be safe and effective in the pediatric population.^5
–7,9

Children with a bleeding diathesis present a unique challenge to the urologist. There are limited data on the intervention for stones in these patients with no reports in the pediatric literature. From the adult literature, the absolute contraindications to PCNL and SWL in patients with bleeding diathesis are well established.^10,11 This leaves ureteroscopy as the modality of intervention in these patients.

We hypothesize that ureteroscopy can be performed safely in children with a coagulopathy who need intervention for urinary tract calculi. We report on the flexible ureteroscopic experience at the Children's Hospital of Philadelphia from July 1, 2004, to June 30, 2011. To our knowledge, this is the only series of pediatric ureteroscopy in this patient population.

Patients and Methods

We conducted an Institutional Review Board approved review of a prospectively maintained database of 890 patients with the diagnosis of urinary calculi between 2004 and 2011. Patients who received a diagnosis of a bleeding diathesis are uniquely identified in the database. Indications, operative details, and outcomes are prospectively recorded. Operative access, operative times, intraoperative complications, stone-free status, and postoperative complications were evaluated. Stone burden was measured in millimeters.

All ureteroscopic procedures were performed using general anesthesia after a failed conservative trial of spontaneous stone passage. No active dilation of ureteral orifices was performed. If stent placement was performed before ureteroscopy, the duration the stent was left in place before the next procedure was at least 1 week. When lithotripsy was necessary, a holmium:yttrium-aluminum-garnet (YAG) laser with settings of 0.6 J and 6 Hz was used. Stents left at the conclusion of ureteroscopy remained in place for at least 1 week.

Stone clearance was assessed intraoperatively by direct ureteropyeloscopy and by postoperative imaging. Follow-up imaging consisted of ultrasonography, abdominal plain radiography, or noncontrast CT, depending on surgeon discretion. Intraoperative complications were defined as evidence of ureteral injury including ischemia, perforation, avulsion, bleeding, or significant extravasation of contrast on ureteropyelography. Postoperative complications were defined as worsening hydroureteronephrosis, ureteral stricture development, bleeding necessitating transfusion, or other untoward events necessitating additional surgical intervention. All stones were sent for analysis, and patients were routinely referred to the nephrology department for evaluation.

Results

During a 7-year period, a total of five children underwent 7 ureteroscopic and 10 cystoscopic procedures for urinary calculi. The 10 cystoscopic procedures included stent insertion or stent removal. Of the seven ureteroscopic procedures, in four of them stents were left on a string to be removed later in the office. The mean patient age was 72.4 months at the time of the procedure with a range of 49 to 123 months. There were three boys and two girls. Mean follow-up was 29.7 months (range 8–79 mos). Mean stone burden was 6.1 mm (range 3–14 mm) with an average of 1.3 stones per patient.

No ureters were actively dilated. Of the five patients, four underwent stent placement before ureteroscopy to minimize potential ureteral trauma based on a known diagnosis of bleeding disorder. The remaining patient underwent stent placement before ureteroscopy based on her age (49 months) and inability to access the ureter with a flexible ureteroscope at the initial procedure; she was not known to have a bleeding disorder at the initial procedure. Flexible ureteroscopy was performed in all cases regardless of stone location. Stone clearance was 100% (7/7) for the remaining ureteroscopic procedures.

Stone analysis revealed calcium oxalate monohydrate (two patients), calcium oxalate monohydrate with calcium phosphate mixed at 70%/30% (one patient), calcium oxalate dihydrate (one patient), and calcium phosphate (one patient). Analysis of the 24-hour urine samples of each patient demonstrated low volume in 5/5 patients, low citrate in 5/5, and high urinary sodium in 2/5. One patient was found to have renal tubular acidosis.

One procedure (6%, 1/17 procedures) was complicated by prolonged and excessive hematuria postoperatively. This female patient subsequently received a diagnosis of a bleeding disorder because of this persistent gross hematuria afterureteral stent placement. Interestingly, bilateral ureteral stones were first diagnosed in her after consultation for urinary retention secondary to blood clots. This same patient needed a transfusion of a unit of packed red blood cells after initial stent placement. No other postoperative complications were identified.

The responsible bleeding disorder was von Willebrand disease (vWd) in all patients. Once the diagnosis of vWd was known, all patients were treated with either desmopressin acetate (DDAVP) or von Willebrand factor/factor VIII complex (vWF/FVIII, Humate-P^®) before their interventions based on consultation with the hematology department. This included both endoscopy and removal of stents on a string in the office. No patient needed a transfusion after pretreatment with either of these products.

Discussion

During the past decade, there has been a dramatic rise in the overall incidence of pediatric urolithiasis.¹² The overall incidence of pediatric urolithiasis ranges from 0.1% to 5%, and reported prevalence accounts for 1 in 1000 to 1 in 7600 hospitalizations in the United States.¹³ Since its first description by Ritchey and associates¹⁴ in 1988, the adoption of pediatric ureteroscopy has been slow because of initial limitations of instrument size and optical image quality, as well as concerns of ureteral ischemia/injury/perforation, ureteral stricture, and induction of vesicoureteral reflux from the manipulation of small caliber pediatric ureters. These concerns led many to advocate SWL as a primary modality for pediatric stone therapy. SWL, however, is contraindicated in patients with bleeding disorders.¹¹

In terms of overall safety, pediatric ureteroscopy has been validated as a safe modality in several contemporary series with complication rates ranging between 1.3% to 5.2%.^5,15 Our series, comprised solely of flexible ureteroscopy, corroborates this low complication rate even in this population at risk for bleeding complications. With mean follow-up of 29.7 months, there was a short-term complication rate of 6% (prolonged bleeding necessitating transfusion), and there were no long-term postoperative complications in this series.

Ureteroscopy and use of the Holmium:YAG laser has been performed safely in the adult population with bleeding diatheses.^16
–18 The coagulopathy in most of these patients is secondary to warfarin that is prescribed for other comorbidities.^16,17 Despite the overall safety and efficacy of the procedure in this at-risk population, significant bleeding complications were described in a small percentage of patients by Watterson and colleagues.¹⁷ The 3% rate experienced in their adult study is comparable to the rate experienced in our pediatric cohort. Stone-free rates do not appear to be affected by the bleeding abnormality.¹⁸

The incidence of vWd in the general population is estimated to be between 0.6% and 1.2%.¹⁹ The disease is inherited in an autosomal dominant fashion, and it is the most common hereditary bleeding disorder.²⁰ Abnormal adhesion and aggregation of platelets results from a defective vWF that normally forms a complex with FVIII in the clotting cascade.¹⁹ Three types of vWd have been identified: Type 1, partial deficiency of normal vWF; type 2, functionally abnormal vWF; type 3, complete absence of vWF.²⁰

Phenotypic expression of the disease is variable. Ziv and Ragni²¹ demonstrated that abnormal postoperative bleeding is the most common initial symptom and manifests in approximately 50% of those with bleeding symptoms. They further identified ear/nose/throat procedures and circumcision as among the most common procedures to present with bleeding complications secondary to vWd. Their research also showed that a significant majority of the patients with postoperative bleeding complications (89%) could have been identified preoperatively with a good family history and personal bleeding history, emphasizing the importance of determining these elements of our patients' histories.

DDAVP helps to address the coagulopathy by increasing plasma levels of vWF and factor VIII.²² The mechanism is not completely understood. The recommended dosage is 0.3 μg/kg by slow intravenous infusion or subcutaneous injection; alternatively, fixed doses of 300 μg in adults and 150 μg in children can be given by intranasal spray.²² Side effects can include headache, flushing, tachycardia, hyponatremia, seizures, and cerebral edema.^22,23 DDAVP is not effective for all patients with vWd. This medication seems most beneficial in type 1 vWd, but is relatively ineffective in type 3 vWd. Evidence-based guidelines have been developed by the National Heart, Lung, and Blood Institute to address the potential for excessive bleeding after surgery.²⁴ These guidelines specify that in situations in which DDAVP is ineffective (type 2 and 3 vWd, refractory type 1 vWd) or when DDAVP is contraindicated, the use of vWF/FVIII for patients is recommended.

This is a post hoc analysis of a prospectively maintained database of pediatric stone patients, which makes this review retrospective in nature. Other limitations include the small sample size. While this group of patients is not commonly encountered, it is important for the pediatric endourologist to be familiar with this group's potential morbidity and specific management.

Conclusion

Pediatric flexible ureteroscopy appears to be a highly efficacious and safe modality in the management of pediatric stone disease in patients with vWd. Patients with a history of vWd and urolithiasis may be at increased risk for transfusions and other bleeding complications related to the stone disease and any subsequent interventions. Pretreatment with DDAVP or vWF/FVIII, given in consultation with a hematologist, may help to decrease these potential complications. These findings may be applicable to other bleeding disorders in pediatric patients when surgical stone intervention is necessary.

Footnotes

Acknowledgments

The authors would like to thank Aileen Schast, Ph.D., for her observations and continued assistance with research projects such as this one.

Disclosure Statement

No competing financial interests exist.

The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government.

Abbreviations Used

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