Clinical Perspective
Genitourinary Imaging
November 2011

Spontaneous Suburothelial Hemorrhage in Coagulopathic Patients: CT Diagnosis

Abstract

OBJECTIVE. The objective of our study was to identify and describe the spectrum of CT findings in patients with coagulopathy-induced suburothelial hemorrhage involving the renal collecting system.
CONCLUSION. CT findings of suburothelial hemorrhage are often subtle and are best appreciated on unenhanced CT scans because of the high density of the hemorrhage. After contrast injection, uniformly thickened soft tissue enveloping the collecting system is suggestive of this condition. Clinical information regarding the presence of coagulopathy is essential for the radiologist to entertain this relatively rare diagnosis.
CT plays a major role in the evaluation of patients presenting with abdominal pain and hematuria. Spontaneous suburothelial renal sinus hemorrhage is a very rare cause of hematuria that is often accompanied by abdominal or flank pain [1]. It is most often associated with a bleeding diathesis, mainly secondary to anticoagulant therapy [211]. The clinical presentation and radiologic findings of suburothelial pelvic hemorrhage overlap with those of transitional cell carcinoma. At least 30 cases have been reported of nephrectomy having been performed for this benign and reversible condition because it was mistaken for a malignant tumor [1].
The aim of this retrospective study was to describe the clinical presentation and emphasize the CT findings of suburothelial hemorrhage in patients with coagulopathy to raise awareness about this rare entity. Radiologists are more likely to consider this diagnosis when they attain increased familiarity with this condition. Clinicians should inform the radiologist of anticoagulant treatment or a bleeding diathesis in a patient presenting with hematuria.

Materials and Methods

The institutional review boards granted permission for this retrospective cohort study and waived informed consent.

Patients

After identification of an index case of suburothelial hemorrhage at the first author’s home institution in July 2009, all subsequent cases of sub urothelial hemorrhage were identified prospectively at this home institution and two others with which the first author is affiliated. This yielded a total of seven cases of suburothelial hemorrhage in coagulopathic patients from three institutions during a period of approximately 18 months (July 2009–December 2010). From a review of their medical records, we recorded the clinical presentation, indication for oral anticoagulant treatment, and international normalized ratio (INR) measurement. The study group was composed of five men and two women ranging in age from 31 to 72 years, with a mean age of 48 years. Six patients presented with abdominal or flank pain that had started from several hours up to 5 days before admission. Five of the six patients with abdominal or flank pain presented with macrohematuria, and one with microhematuria. The last patient had painless hematuria.
Six patients were on warfarin (Coumadin, Bristol-Myers Squibb) treatment. The indications for anticoagulation included prior deep vein thrombosis and pulmonary embolism in two patients, aortic valve replacement in two, atrial fibrillation in one, and coagulation disorder (likely antiphospholipid syndrome) in one. The INR at the time of admission was markedly above the desired therapeutic range (2.0–4.0) in five patients, ranging from 5 to 12 (average INR, 8.1). In the sixth patient, the INR was elevated but was still within therapeutic range. The seventh patient had severe thrombocytopenia with a platelet count of 4000 × 103/μL. This latter patient presented with painful macroscopic hematuria and also with epistaxis, oral mucosal bleeding, and lower extremity petechiae. A presumptive diagnosis of thrombotic thrombocytopenic purpura (TTP) was made.

CT Technique

CT studies were performed on a 16- or 64-MDCT scanner (Mx 8000, Philips Healthcare; Sensation 64, Siemens; or LightSpeed VCT, GE Healthcare).
The following scan parameters were used for the 16-MDCT scanner: 16 × 1.5 mm collimation, 2-mm slice thickness, 1-mm scan interval, 120 kVp, and 250 mAs. For the 64-MDCT scanner, we used 64 × 0.625 mm collimation, 0.9-mm slice thickness, 0.45-mm slice interval, 120 kVp, and 300 mAs.
In all cases, 3-mm-thick axial slices were reconstructed and sent to the PACS. For the contrast-enhanced portions of the examinations, most patients received approximately 125 mL of iohexol (Omnipaque 350, GE Healthcare) administered IV at a rate of 3 mL/s by means of a mechanical power injector.
All studies included an unenhanced phase, which is part of our standard imaging protocol for evaluation of patients with hematuria. Six of the seven patients underwent additional scanning during the nephrographic and pyelographic phases, with images acquired at a delay of 70 seconds and 3 minutes, respectively, after IV contrast injection.

Image Analysis

The CT studies were evaluated by two abdominal imaging radiologists with 20 and 23 years’ experience. The studies were assessed with respect to the following: the appearance of the collecting system on unenhanced scans and on various postcontrast phases; universus bilateral involvement; the presence of ureteral involvement, perinephric or periureteral stranding, or hydronephrosis; and additional pertinent findings suggesting bleeding diathesis.

Results

Abnormal CT findings were confined to the suburothelial layer of the collecting system in all seven patients.
Unenhanced images showed high-density mural thickening of the renal pelvic urothelium in all seven patients (Fig. 1A) that extended into the proximal ureter in five (Fig. 1B). Involvement of the collecting system was unilateral in four patients (left kidney, n = 2; right kidney, n = 2) and bilateral in three; in the three bilateral cases, collecting system involvement was asymmetric.
The increased density of the wall compared with the lumen was often subtle and was better appreciated on narrow window settings. In the nephrographic phase, the mural thickening was less conspicuous than on the unenhanced scan and appeared as soft-tissue thickening in the renal pelvis (Fig. 1C). On pyelographic phase images, the mural thickening was well seen and appeared to envelop the renal pelvis and proximal ureter, causing narrowing of the infundibula, renal pelvis, and proximal ureters (Figs. 1D, 1E, and 1F). Despite the encasement of the infundibula, the calyces were dilated in only two cases and dilatation was minimal. These two patients had bilateral involvement with extension into the proximal ureters, which appeared thickened, and had associated perinephric and periureteric fat stranding.
Four of the seven patients underwent follow-up CT likely because of uncertainty about the diagnosis. The follow-up examinations were performed 12 days to 6 months after the first examination. All of these studies showed complete resolution of the findings (Figs. 1G and 1H). We do not have information that accounts for why the remaining three patients did not undergo follow-up imaging.
None of the CT studies revealed any additional findings suggestive of hemorrhage at additional sites.

Discussion

Suburothelial pelvic and sinus hemorrhage is a rare condition with clinical presentation and imaging findings that may mimic a neoplasm of the renal collecting system. It was first described in 1948 by Antopol and Goldman [12]; they reported seven patients presenting with hematuria in whom filling defects in the renal collecting system raised suspicion of neoplasm and led to nephrectomies being performed. The term “Antopol-Goldman lesion” has since been used to denote suburothelial pelvic hematoma involving the renal pelvis, which more effectively describes this entity. Since the initial report, approximately 30 patients with this benign condition have undergone unnecessary nephrectomies on the basis of clinical presentations and radiologic studies that could not rule out a transitional cell neoplasm [1, 13].
These recurring diagnostic errors likely reflect a lack of awareness of the relatively rare phenomenon of suburothelial pelvic hemorrhage. Although the imaging literature contains isolated case reports about this entity, ours is the first case series focusing on the appearance of this entity in the era of MDCT using multiple acquisition phases and multiplanar reformatting.
The diagnosis of suburothelial hemorrhage is rarely considered before imaging. The most common indication for imaging in these patients is painful hematuria. Familiarity with the appearance of suburothelial hemorrhage on different phases is important because the diagnosis can be established on the basis of these, often subtle, findings. Awareness of this entity should prompt inquiry into the presence of coagulopathy when the characteristic imaging features are encountered.
The most frequent clinical presentation of suburothelial pelvic hemorrhage is macroscopic hematuria and acute flank or abdominal pain. The pathogenesis in most of the earlier reported cases remained uncertain, and possible associated factors included trauma, underlying congenital malformations, diabetes, hypertension, renal colic, drug abuse, and amyloidosis [1].
More recently, the association between Coumadin anticoagulant therapy and suburothelial hemorrhage has been established [29]. Other bleeding diatheses, including hemophilia and factor V deficiency, have also been associated with this condition [10, 14]. Six of our seven patients were being treated with Coumadin, and one patient had severe thrombocytopenia thought to be a result of underlying TTP.
On CT, suburothelial hemorrhage manifests as mural thickening of the renal pelvis and upper ureter that may compromise the lumen of the renal pelvis and ureter and cause calyceal dilatation. Suburothelial hemorrhage is best appreciated on unenhanced images, when the high density of the lesion is most conspicuous [5, 8]. These findings are considerably less evident on nephrographic phase images and are easily overlooked because the hemorrhage is masked by the enhancement of the surrounding tissues. On pyelographic phase images, the mural thickening and the intraluminal defects are evident; however, the high density of the lesions typical of either suburothelial hemorrhage or a blood clot cannot be appreciated. Other conditions that are associated with filling defects in the renal collecting system—such as pyeloureteritis cystica, uroepithelial tumor, and vascular impressions from collateral circulation—do not show this high density [15]. Therefore, we conclude that the unenhanced phase is the best one to establish the diagnosis of suburothelial hemorrhage.
Based on prior reports, suburothelial hemorrhage appears to affect the right and left kidneys equally and without sex predilection [1, 13].
Fig. 1A 46-year-old man with bilateral suburothelial hemorrhage extending into proximal ureters. Patient had been on warfarin (Coumadin, Bristol-Myers Squibb) for treatment of atrial fibrillation and presented with 5-day history of abdominal and flank pain; international normalized ratio level was 7.8.
A, Unenhanced scan shows high density outlining periphery of renal pelves bilaterally (arrows).
Fig. 1B 46-year-old man with bilateral suburothelial hemorrhage extending into proximal ureters. Patient had been on warfarin (Coumadin, Bristol-Myers Squibb) for treatment of atrial fibrillation and presented with 5-day history of abdominal and flank pain; international normalized ratio level was 7.8.
B, From more caudad slice than A, this unenhanced scan shows thickening of both proximal ureters with high density outlining ureteral wall (arrows) that is more prominent on right. There is also mild infiltration of periureteral fat.
Fig. 1C 46-year-old man with bilateral suburothelial hemorrhage extending into proximal ureters. Patient had been on warfarin (Coumadin, Bristol-Myers Squibb) for treatment of atrial fibrillation and presented with 5-day history of abdominal and flank pain; international normalized ratio level was 7.8.
C, On corticomedullary phase image, thickening along renal pelvis (arrows) appears less pronounced than on unenhanced scans.
Fig. 1D 46-year-old man with bilateral suburothelial hemorrhage extending into proximal ureters. Patient had been on warfarin (Coumadin, Bristol-Myers Squibb) for treatment of atrial fibrillation and presented with 5-day history of abdominal and flank pain; international normalized ratio level was 7.8.
D, Pyelographic phase image obtained at same level as A shows marked circumferential thickening of both renal pelves encasing collecting system (arrows). High density of lesion seen on unenhanced scans is no longer evident.
Fig. 1E 46-year-old man with bilateral suburothelial hemorrhage extending into proximal ureters. Patient had been on warfarin (Coumadin, Bristol-Myers Squibb) for treatment of atrial fibrillation and presented with 5-day history of abdominal and flank pain; international normalized ratio level was 7.8.
E, More caudad slice on pyelographic phase shows thickening of proximal ureters (arrows), which is more prominent on right. High density outlining ureteral wall that was observed on unenhanced scan (B) is no longer visible. Mild infiltration of fat is seen around ureters.
Fig. 1F 46-year-old man with bilateral suburothelial hemorrhage extending into proximal ureters. Patient had been on warfarin (Coumadin, Bristol-Myers Squibb) for treatment of atrial fibrillation and presented with 5-day history of abdominal and flank pain; international normalized ratio level was 7.8.
F, Coronal reformat at pyelographic phase shows soft tissue encasing renal pelves bilaterally (arrows). Note lack of dilation of collecting system in spite of narrowed lumen of collecting system.
Fig. 1G 46-year-old man with bilateral suburothelial hemorrhage extending into proximal ureters. Patient had been on warfarin (Coumadin, Bristol-Myers Squibb) for treatment of atrial fibrillation and presented with 5-day history of abdominal and flank pain; international normalized ratio level was 7.8.
G, Follow-up axial unenhanced phase scan obtained 12 days after A–F shows resolution of high-density thickening along renal pelvis.
Fig. 1H 46-year-old man with bilateral suburothelial hemorrhage extending into proximal ureters. Patient had been on warfarin (Coumadin, Bristol-Myers Squibb) for treatment of atrial fibrillation and presented with 5-day history of abdominal and flank pain; international normalized ratio level was 7.8.
H, Follow-up axial pyelographic phase scan obtained 12 days after A–F shows complete resolution of suburothelial hemorrhage.
Hydronephrosis is not a common feature in spite of the encasement of the renal infundibula by hemorrhage. Only two patients in our study group had a mild degree of hydronephrosis and also showed perinephric and periureteric fat stranding, reflecting a component of obstruction. The absence of hydronephrosis was likewise noted in most prior reports [5, 6, 8], and, when present, hydronephrosis was very mild [2, 7, 10].
Involvement of the proximal ureter with suburothelial hemorrhage is not rare. The ureteral wall appears remarkably thickened in a concentric fashion, but this thickening does not cause significant dilatation of the renal collecting system [4, 6].
In contrast to prior case reports, we encountered bilateral involvement of the kidneys in three of the seven patients in the study group—a much higher rate than has been reported to date in the literature. We found no prior case report of bilaterality in the English-language literature perhaps because most of the cases were reported only after nephrectomy for suspected malignancy. In contrast, bilaterality of the lesions would more likely indicate a systemic disorder than a neoplastic lesion and therefore would more likely be treated conservatively and thus not reported.
In patients with suburothelial hemorrhage, the hemorrhage tends to resolve rapidly once Coumadin is withdrawn and the coagulopathy had been corrected. We observed complete resolution in all four patients who had a follow-up study, including one follow-up study performed as soon as 12 days after the initial study. Similarly, several reports in the literature documented improvement 1 week after Coumadin withdrawal or coagulopathy correction [6] and complete resolution as early as 2–4 weeks [2, 5, 7, 8, 10]. There are no guidelines recommending follow-up CT to document resolution. It is possible that follow-up studies can be avoided with increased familiarity with this condition and increased confidence in the diagnosis based on the typical clinical, laboratory, and CT findings.
Simultaneous hemorrhage in another organ might suggest that the underlying cause of the abnormality in the renal pelvis is hemorrhage, but this finding is very rare. None of the patients in our series had CT findings suggestive of concurrent hemorrhage affecting another organ, although the patient with severe thrombocytopenia had epistaxis, oral mucosal bleeding, and lower extremity petechiae. Similarly, only two patients with suburothelial hemorrhage on Coumadin treatment in prior reports had CT evidence of spontaneous hemorrhage affecting an additional site, the jejunum and the perirenal space, respectively [9]. Thus, it appears that suburothelial hemorrhage is usually the sole manifestation of coagulopathy in these patients.
Our study has several limitations. There is no gold standard other than pathologic proof to confirm the diagnosis. Nevertheless, the purpose of this report is to increase awareness about this benign condition and prevent unnecessary nephrectomies in patients presenting with hematuria who are found to have urothelial thickening on CT. The study group is small and includes only seven patients. The scanning was not uniform given that two of the patients underwent only unenhanced CT. In addition, only four of the seven patients had follow-up CT studies documenting resolution. However, there are no established guidelines for following suburothelial hemorrhage on CT. With the increasing concern regarding radiation exposure, the need for CT follow-up is questionable in the presence of pathognomonic findings of intramural hemorrhage involving the collecting system on unenhanced scans. Clinical follow-up documenting resolution of hematuria may be sufficient.
We conclude that suburothelial hemorrhage has specific findings on CT, especially in the unenhanced phase. Although this condition could easily be mistaken for a neoplasm of the collecting system, it is important for the radiologist to entertain the diagnosis of hemorrhage involving the kidney because many patients are on permanent anticoagulant treatment and therefore at some risk of bleeding. Familiarity with the CT appearance of this entity should enable radiologists to arrive at the correct diagnosis, thereby preventing unnecessary intervention.

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References

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Information & Authors

Information

Published In

American Journal of Roentgenology
Pages: W887 - W890
PubMed: 22021537

History

Submitted: January 11, 2011
Accepted: March 29, 2011

Keywords

  1. Coumadin-induced hemorrhage
  2. CT
  3. kidney
  4. renal pelvis
  5. warfarin-induced hemorrhage

Authors

Affiliations

Gabriela Gayer
Department of Radiology, Assaf Harofeh Medical Center, Zrifin, Israel.
Department of Diagnostic Imaging, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Present address: Department of Radiology, Stanford University Medical Center, Stanford, CA 94305-5105.
Terry S. Desser
Present address: Department of Radiology, Stanford University Medical Center, Stanford, CA 94305-5105.
Marjorie Hertz
Department of Diagnostic Imaging, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Radiology, Sheba Medical Center, Ramat Gan, Israel.
Alexandra Osadchy
Department of Diagnostic Imaging, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Radiology, Meir Medical Center, Kfar-Saba, Israel.
Bruce L. Daniel
Present address: Department of Radiology, Stanford University Medical Center, Stanford, CA 94305-5105.
Rivka Zissin
Department of Diagnostic Imaging, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Radiology, Meir Medical Center, Kfar-Saba, Israel.

Notes

Address correspondence to G. Gayer ([email protected]).

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