Haematuria is not an uncommon presenting sign in dogs. An attempt to localise the source of the bleeding should be made; local disease of the urogenital tract, systemic disease and bleeding disorders warrant consideration. This case report describes the investigation of haematuria in a 10-year-old male neutered (MN) Labrador. The clinical examination findings, diagnostic and treatment options, along with prognosis for transitional cell carcinoma as a cause of haematuria, are discussed.
A 10-year-old 40 kg male neutered (MN) Labrador was presented for haematuria of two weeks' duration. The owner reported one episode of inappropriate urination in the house and stranguria over the past two days. The dog was otherwise bright and active, with no alterations in drinking or appetite. The dog had no previous medical history and vaccination and worming were up to date.
The dog was bright and panting but with no increased effort and no abnormal sounds detected on auscultation. Mucous membranes were pink and moist with a capillary refill time of two seconds. Heart rate and rhythm were within normal limits and a murmur was not detected on cardiac auscultation. Body condition score was above ideal at 4/5. The dog was tense on palpation of the caudal abdomen. There was no detectable peripheral lymphadenopathy. The dog was castrated and palpation of the prostate per rectum was unremarkable. No abnormalities of the penis or prepuce were identified. Temperature was normal (38°C). The owner considered urine flow to be normal and the frequency of urination unaltered.
Differential diagnoses considered included disease of the lower urinary tract (LUT) including infection, inflammation, or neoplasia affecting the bladder, urethra or prostate, in addition to renal haematuria, systemic disease or bleeding disorder (Table 1).
Table 1. Problem list and differential diagnosis. (The list is not exhaustive. Those considered most likely are shown in italics)
•Pain– from caudal abdominal organs including bladder, prostate, gastrointestinal tract, • referred spinal pain, abdominal muscle discomfort
The presence of both stranguria and haematuria made LUT disease the most probable cause of the clinical signs. A systemic bleeding disorder was considered unlikely based on the clinical examination. Permission for full haematology to assess platelet numbers and clotting times was not provided due to restricted finances.
A free catch urine sample obtained for ‘dipstick’ assessment demonstrated microscopic haematuria which was confirmed by urinalysis at an external laboratory (Table 2). Urine specific gravity measured with a refractometer was 1.012. Polyuria/polydipsia had not been noted but repeat measurements from numerous samples throughout the day were similar. Reduced renal concentrating ability was considered and discussed with the owner.
Table 2. Urinalysis results
Mid yellow, clear
Urine specific gravity (USG)
<1.008 Hyposthenuria 1.008–1.012 Isosthenuria >1.012 Hypersthenuria Usual range in healthy dogs 1.015–1.040
Urine protein: creatinine ratio
Small amounts of protein can be normal. LUT infection/inflammation can affect protein content. Interpret in light of USG and evaluate urine sediment.
Small amount of bilirubin may be found in the urine of normal dogs
Abnormal. Very small amounts normal if cystocentesis sample.
RBC /high power field (hpf)
< 3/ hpf
No evidence of renal disease or crystalluria
Treatment with 12.5 mg/kg amoxicillin-clavulanic acid (500 mg Synulox Palatable Tablets; Pfizer Ltd) q 12h and 0.1 mg/kg meloxicam (Metacam; Boehringer) q 24h, both administered orally, was initiated whilst external urinalysis results were pending. Clinical signs improved but microscopic haematuria, as determined by repeat ‘dipstick’ assessment, persisted. Urine culture was negative.
Further investigations were targeted in view of the restricted finances. PCV and basic serum biochemistry were unremarkable (Table 3). An abdominal ultrasound scan and a right lateral radiograph centred on the caudal abdomen were performed.
Table 3. Biochemistry results
Parameter measured (units)
Total Protein (TP) (g/l)
The abdominal radiograph revealed a small bladder with organ location and outlines being considered normal. Mild lumbosacral spondylosis was noted but considered incidental. There was no evidence of radio-opaque uroliths within the entire urinary tract.
The ultrasound scan (Figs. 1a and 1b) revealed a mass in the trigone region measuring approximately two by three centimetres, which appeared to be invading the wall and protruding into the bladder lumen. The bladder neck, urethra and prostate appeared unaffected. No abnormalities of the kidneys were detected.
Table 4. Ultrasonographic features of the bladder
Normal feature of bladder
Normal wall thickness: 1–2mm (full) to 5mm (empty)
20–30 mm in affected area due to focal thickening and sessile mass extending into lumen (19 mm × 27.5 mm)
Swirling hyperechoic material within lumen
A rigid 10F urinary catheter (Baxter) was passed without difficulty. Ultrasound guidance was used to obtain catheter suction samples of the mass. A smear was made and the remaining sample material placed in labelled plain, ethylenediamine tetra-acetic acid (EDTA) and EDTA with formalin pots for analysis at an external laboratory.
The fluid analysis revealed mild haematuria and a population of epithelial cells demonstrating nuclear criteria of malignancy including anisokaryosis and increased nuclear to cytoplasmic ratio. Neutrophil numbers were low and infectious agents were not identified.
Due to the location of the mass, and in the absence of findings supportive of an inflammatory process (negative urine culture, absence of active urine sediment to indicate urinary tract inflammation/infection, no history of previous urinary tract disease) which could have induced epithelial changes, the morphological appearance of the epithelial cells was considered consistent with the presence of a transitional cell carcinoma (TCC) of the bladder. Other differentials including papillomatous (polypoid) cystitis and urothelial dysplasia were considered less likely. Fig. 2 provides an example of the typical cytological appearance of a TCC.
Further investigation including surgical biopsy was declined. Continued treatment with meloxicam (Metacam; Boehringer) was discussed along with other chemotherapy options (see discussion). Treatment with 0.3 mg/kg piroxicam (Piroxicam; Generics UK Ltd) q 24h was started 48 hours after meloxicam treatment had been ceased.
FOLLOW UP AND OUTCOME
The dog was examined at three and six months post diagnosis. Physical examination was unremarkable and the dog had not demonstrated any gastrointestinal side effects of piroxicam administration. The owner reported absence of gross haematuria and only infrequent stranguria. Urinalysis remained culture negative. Renal parameters were within normal limits. Repeat ultrasound scan for monitoring was declined. The owner considered the dog to have an excellent quality of life.
Seven months after diagnosis the dog deteriorated acutely and was presented collapsed. Further investigation and treatment were declined and the owners elected for the dog to be euthanased.
Clinical signs and diagnostic methods
The timing of haematuria relative to urine voiding can aid in localising the source of bleeding (Table 5). Ideally both a free catch and cystocentesis sample would be assessed to determine the location. Blood throughout the urine stream, known as ‘total’ haematuria, can be found with pathology of the bladder, ureters and kidneys or systemic bleeding disorders. It results in pink coloured urine as seen in this case (Grauer 2009, Kenefick 2010). The dog was not demonstrating any other signs attributable to an underlying bleeding disorder; however haematology including a smear for platelet assessment and clotting times should be performed for completeness.
Table 5. Guide to timing and location of haematuria
Timing of haematuria - the following explanations can be useful as a guide, but overlap occurs
Possible origin of haematuria
Initial– blood seen at the start of urine voiding
Lower urinary tract (bladder neck, urethra, vagina, vulva, penis or prepuce) Extra-urinary causes (proestrus, infection of uterus, prostatic disease or neoplasia of the genital tract)
Terminal– blood seen towards the end of urine voiding
Upper urinary tract (bladder, ureters, kidneys – erythrocytes settle in bladder and are expelled towards the end of voiding)
Total– blood throughout urine voiding/pink urine
Bladder, ureters or kidneys
A positive result on a urine dipstick may be due to pigmenturia other than blood (Kenefick, 2010), hence confirmation with urine microscopy in this case. Urine culture can be used to exclude chronic inflammation due to an underlying urinary tract infection as the cause of the haematuria. It is recommended that culture be performed on a sample obtained via cystocentesis since free catch samples may be contaminated. However, it is not uncommon for low numbers of red blood cells to be detected after collection of urine by cystocentesis.
Ultrasound has been recommended as the primary imaging modality for investigation of patients with haematuria or dysuria due to the ability to evaluate the majority of the urinary tract and it can also facilitate sample collection. When compared to intravenous urography and double-contrast cystography, it was the only imaging modality where bladder masses were detected in 100 per cent of dogs. However the limitations of not being able to fully evaluate the intra-pelvic urethra were acknowledged (Leveille et al., 1992). Where ultrasound is not available, radiography for positive and double-contrast retrograde urethrocystography can be utilised. Contrast cystography demonstrated a mass or filling defect in 96% of dogs with LUT tumours in one retrospective study, and was therefore considered a useful non-invasive diagnostic method (Norris et al., 1992).
Fine needle aspirate (FNA) of masses of the bladder, prostate or urethra is generally not recommended due to the potential for neoplastic seeding along the needle tract (Nyland et al., 2002). Obtaining a sample via ultrasound guided urinary catheter or cystoscopy is considered preferable (Webster, 2009).
Cystoscopy is a useful diagnostic procedure allowing visualisation of and biopsy collection from the lower urinary and genital tracts. Rigid cystoscopes are utilised in bitches whereas small flexible ‘scopes’ are available for use in male dogs. Cystoscopic biopsies have been shown to be of diagnostic quality in 65% of male dogs and 96% of female dogs compared to 100% with surgical cystotomy biopsies (Childress et al., 2011). However, since few general practices will possess a suitable flexible cystoscope to allow this technique to be performed in male dogs, referral should be considered.
Although urinary catheter samples are an accepted simple minimally invasive method of sample collection which do not require specialised equipment, the limitation of sample yield on accuracy of histological diagnosis has been noted (Lamb et al., 1996). In this case, the sample findings were suggestive of TCC but were insufficient to provide a definitive diagnosis since only cytological and not histological samples are obtained.
The majority of dogs have advanced disease at the time of diagnosis, and may not be surgical candidates (Henry, 2003). Metastatic disease (regional or distant) has been reported to be present in 11% (Henry, 2003) to 31% (Norris, 1992) of dogs at the time of diagnosis of malignant bladder tumours. Accurate histological diagnosis allows implementation of optimal treatment.
Alternative methods of diagnosis have been explored, including use of a ‘bladder tumour antigen test’ originally designed for use in humans. Although sensitivity was found to be good, specificity is low leading to false positive results especially in the presence of haematuria, making it unreliable in differentiating malignant and non-malignant lower urinary tract disease (Billet et al., 2002, Henry et al., 2003).
Management options, expected survival times and potential adverse effects need to be discussed with the owner. The literature reveals a number of methods of management of canine TCC that have been explored including: surgical (debulking, partial cystectomy, cystotomy tubes), radiation, chemotherapy including piroxicam, cisplatin, mitoxantrone and gemcitabine (Marconato et al., 2011), laser ablation (Cerf & Lindquist, 2012) or a combination of these techniques. Regardless of method, however, median survival times (MST) are generally less than a year.
The non-steroidal anti-inflammatory drug (NSAID) piroxicam has been reported to have antineoplastic properties, although uncertainty exists over the precise mode of action. Although generally well tolerated, piroxicam-induced gastrointestinal adverse effects and subclinical renal papillary necrosis are recognised complications (Knapp et al., 1992).
Complete remission, defined as disappearance of all clinical and radiographic evidence of tumour for a minimum of 30 days, was seen in 2 of 34 dogs treated with piroxicam in one study (Knapp et al., 1994), although MST was only 181 days. Piroxicam is not licensed for use in dogs and therefore other NSAIDS such as meloxicam could be considered initially as alternative treatments.
MST for piroxicam used in combination with mitoxantrone has been reported at 291 days which is longer than reported for piroxicam alone (Henry et al., 2003). Treatment with piroxicam and mitoxantrone in combination with coarse fraction radiation has been evaluated and found to be well tolerated (Poireir et al., 2004). It was concluded however, that since MST in this small pilot study was 326 days, this combination offered limited advantage over piroxicam and mitoxantrone alone.
Gemcitabine is reported to be a promising chemotherapeutic agent in human medicine and when used in dogs in combination with piroxicam an improvement in clinical signs was noted (Marconato et al., 2011). However, like many other treatments evaluated, the combination failed to significantly improve overall survival time.
Cisplatin administered in combination with piroxicam has been shown to induce remission more frequently than cisplatin alone. Renal toxicity was a dose-limiting factor due to the direct nephrotoxic effect of cisplatin in addition to NSAIDs induced negative effects (Knapp et al., 2000). Dogs with TCC are at risk of obstructive disease, which can contribute to renal failure (Henry et al., 2003). Monitoring of renal parameters in dogs receiving treatment for TCC is therefore advisable.
Advice from a clinical oncologist can be sought where appropriate. Oncologists currently consider treatment with piroxicam and mitoxantrone to be the primary standard of care providing a MST of 291 days and a 35% response rate, with other options being explored if response to treatment is poor.
Haematuria, particularly if persistent, warrants further investigation which may include complete urinalysis, blood samples including haematology and serum biochemistry and diagnostic imaging techniques. Transitional cell carcinoma may affect the bladder, prostate or urethra. Treatment is often palliative due to the extent of the disease at the time of diagnosis and must be decided on an individual basis to provide relief of lower urinary tract signs whilst minimising adverse side effects.
CONTINUING PROFESSIONAL DEVELOPMENT
In order to test your understanding of this article, answer these multiple choice questions, or if you are a subscriber, go online at http://www.ukvet.co.uk, and find many more multiple choice questions to test your understanding.
1If a bladder mass suspicious of Transitional Cell Carcinoma is discovered, a fine needle aspirate should be performed when:a. Alwaysb. Neverc. To obtain a diagnosis when alternative sampling techniques are not available
2Haematuria can be associated with which of the following:a. An infection of the bladderb. A tumour of the bladderc. disease of the prostated. Thrombocytopeniae. All of the above
3The timing of haematuria in relation to the urine voided (choose all that apply):a. Can help localisation of the source of the bloodb. Is of little diagnostic valuec. Can be classified as initial, terminal or total haematuria, where ‘total haematuria’ relates to blood mixed throughout the urine voided