Aortic thromboembolism in a basset hound-beagle crossbred dog with protein-losing nephropathy

Abstract

A 12-year-old neutered male basset hound-beagle crossbred dog with a history of protein-losing nephropathy was presented because of acute weight-bearing right hind limb lameness with hind-end paresis and intermittent splaying. The condition was painful and progressed to non-ambulatory paraparesis. The dog was referred to an emergency and specialty hospital where a diagnosis of aortic thromboembolism was confirmed. This case illustrates the challenge in diagnosing and determining the cause of aortic thromboembolism in dogs.

A 12-year-old neutered male basset hound-beagle crossbred dog was presented because of acute weight-bearing lameness of the right hind limb. The patient had a history of protein-losing nephropathy (PLN), and was being managed long-term on benazepril, 1 mg/kg body weight (BW), PO, q24h obtained from an unidentified pharmacy. Following a short walk, the owners noticed the dog was limping on the right hind limb and periodically holding it off the ground. Intermittent paresis and splaying of the hind-end were also described. Neurological examination of the patient found no abnormalities and no neck or back pain. There was crepitus and discomfort on flexion and extension of the right hind limb stifle and decreased hip extension bilaterally. A slight medial buttress could be palpated on the medial aspect of the right hind limb stifle; however, no joint laxity was noted and there was no cranial drawer sign. Based on the history and physical examination, soft tissue injury, degenerative joint disease, and partial cruciate ligament rupture were suspected. Radiographic examination of the hind limbs revealed bilateral degenerative joint disease of the hips, and mild fluid distension of the right stifle. With this information, the owners opted for conservative management with gabapentin (Teva-Gabapentin Capsules; Teva Canada, Toronto, Ontario), 10 mg/kg BW, PO, q8–12h and restricted exercise.

The patient deteriorated overnight and was presented again the following day with pain in the hind-end and non-ambulatory paraparesis. No neck or back pain was detected, and deep pain was intact. The patient had motor function in both hind limbs but was unable to stand without support. Proprioceptive deficits were present in both hind limbs but were worse in the left hind limb. Cranial nerve examination and mentation were normal, and cutaneous trunci, perineal, and spinal reflexes were intact but weaker in the left hind limb.

The patient was ultimately referred to an emergency and specialty hospital, where the veterinarians experienced difficulty palpating a left femoral pulse and noted that the left hind limb felt cold. Left hind limb lactate and potassium concentrations were elevated and glucose was decreased compared to the other limbs. A distal aortic thromboembolism with bilateral extension into the proximal femoral arteries was confirmed by abdominal ultrasound. The patient was continued on gabapentin (Teva Canada),10 mg/kg BW, PO, q8–12h, and started on telmisartan (Boehringer Ingelheim, Burlington, Ontario), 1 mg/kg BW, PO, q24h, amlodipine (Summit Veterinary Pharmacy, Aurora, Ontario), 0.4 mg/kg BW, PO, q12h, rivaroxaban (Xarelto Tablets; Bayer, Mississauga, Ontario), 0.5 mg/kg BW, PO, q24h, and clopidogrel (Clopidogrel Bisulfate; Summit Veterinary Pharmacy), 0.8 mg/kg BW, PO, q24h. He was discharged with a grave prognosis but was presented again shortly thereafter with a 24-hour history of urine retention and dribbling. On physical examination, the patient was hypertensive, mucous membranes were injected, and a grade I/VI left-sided heart murmur was auscultated. The bladder could no longer be expressed on palpation and frequent catheterization was required, which became increasingly difficult. No significant improvements in ambulation were seen and the left hind limb nailbeds became cyanotic. On account of the patient’s worsening condition and discomfort, the owners elected euthanasia.

Discussion

Aortic thromboembolism (ATE) is recognized as a common complication of cardiac disease in cats. In conditions such as hypertrophic cardiomyopathy, abnormal blood flow in an enlarged left atrium can result in thrombus formation with embolization to the distal aorta (1,2). Feline patients suffering from ATE are commonly presented in pain with an acute onset of paraparesis or paraplegia, weak or absent femoral pulses, cold distal limbs, and nail and footpad cyanosis (3). In dogs, on the other hand, ATE is rare (4) and often associated with a predisposing condition such as an immune-mediated disease, neoplasia, systemic inflammation, sepsis, cardiac disease, protein-losing nephropathy (PLN), protein-losing enteropathy, or systemic hypertension (2,5–8). However, in some cases of ATE in dogs, there are no concurrent conditions and no cause is identified (9).

In contrast to the acute clinical presentation of ATE in cats, dogs can be presented with more chronic clinical signs, such as exercise intolerance with few motor or neurological deficits (6). These dogs are often less severely affected and have longer survival times compared to those that are presented with acute clinical signs (4,6). It has been suggested that the chronicity of clinical signs in some patients could be attributed to the extensive collateral circulation of the canine pelvic limbs, or to incomplete obstruction of blood flow (10,11). There are reports of dogs with blood flow remaining through or around an aortic thrombus (4). If there had been more blood flow remaining through or around the part of the thrombus extending into the right femoral artery of the patient in the present case, this may have explained why the deficits were worse in the left hind limb. It is difficult to know why the patient originally displayed right hind limb lameness. With mild fluid distension noted on radiographs of the right stifle, it is possible that the patient’s initial clinical signs were worse in the right hind limb due to a pre-existing injury or arthritis.

Systemic hypertension has been associated with ATE in dogs (8). The systemic hypertension reported in the present case may have been due to stress associated with the patient’s condition or hospitalization (12). It is possible that systemic hypertension contributed to the development of ATE in this case, or that hypertension caused by stress exacerbated the condition. Since blood pressure measurements were not taken prior to, or at the time of initial presentation, the role of systemic hypertension in the development of ATE in this case is not known. Aortic thromboembolism has also been reported as a potential consequence of cardiac disease in dogs (2). The low-grade heart murmur detected herein was not identified at initial presentation and no echocardiography was performed to confirm cardiac disease as a potential predisposing factor to ATE. Nonetheless, this case might support including careful cardiac auscultation and echocardiography as diagnostic procedures in cases of pelvic limb motor and neurological dysfunction.

The patient in the present case had a history of glomerulonephritis, for which he was managed long-term on benazepril (20 mg, PO, q24h). Protein-losing nephropathy (PLN) has been reported as the most common concurrent disease in dogs with ATE (8). The thromboembolic complications associated with PLN may be due to a decrease in antithrombin activity owing to urinary loss (2,13,14). Additionally, plasma α-globulins are often elevated in patients with PLN and this portion of the serum contains the clot-promoting factors prothrombin and factor VIII (14). The cause of thromboembolism in the present case was not confirmed; however, the literature suggests that the patient could have been in a hypercoagulable state due to PLN, which predisposed him to ATE. There is evidence to suggest that we cannot predict the occurrence of thromboembolism in patients with renal disease based on the degree of proteinuria, hypertension, hypoalbuminemia, or decreased antithrombin activity (15). Nevertheless, it may be prudent to consider aortic thromboembolism as a differential diagnosis in dogs with renal disease that present with hind limb lameness. This case might also support prophylactic anticoagulant use in patients with PLN.

Although not confirmed, it would appear that PLN predisposed the patient in the present case to ATE. Dogs with ATE may not always present with acute pain, cold limbs, absent femoral pulses, and paraparesis or paraplegia, as one might expect since this is the classic presentation of ATE in cats (1,3). The clinical signs of ATE in dogs can be more chronic and non-specific, making it a challenging disease to diagnose. Further studies are needed to provide a better understanding of the conditions that predispose dogs to ATE so that it may be prevented or suspected and diagnosed early in the course of disease.