Segmental aplasia of the caudal vena cava in a dog

Abstract

Ultrasonography, angiography, magnetic resonance imaging, and exploratory laparotomy of a 2-year-old wheaten terrier with lethargy, exercise intolerance, and ascites revealed segmental aplasia of the caudal vena cava with azygos continuation, complicated by thrombus formation. Surgeries were performed on the blind-ended vessel to remove thrombi, enhancing shunting of blood through the azygos vein.

A 2.5-year-old, castrated male wheaten terrier was referred to the Western College of Veterinary Medicine Veterinary Teaching Hospital (WCVM-VTH) with a 6-month history of lethargy and exercise intolerance. Physical examination revealed a quiet, responsive dog with ascites and peripheral venous distension of the hind limbs and ventral abdomen. A complete blood cell (CBC) count showed a mild anemia (red blood cells, 4.17 × 10¹²/L; reference range, 5.5 to 8.5 × 10¹²/L) with abnormal erythrocyte morphology, including slight numbers of keratocytes and schizocytes. The coagulation profile was within the normal reference range (prothrombin time (PT), 7.5 to 9.9 s, partial thromboplastin time (PTT), 9.6 to 13.8 s). Serum biochemical analysis revealed hypoalbuminemia (24 g/L; reference range, 29 to 38 g/L) and increases in urea (12.5 mmol/L; reference range, 3.0 to 10.5 mmol/L), creatinine (212 μmol/L; reference range, 60 to 140 μmol/L), cholesterol (6.79 mmol/L; reference range, 2.50 to 5.50 mmol/L), glucose (7.1 mmol/L; reference range, 3.3 to 5.6 mmol/L), amylase (1105 U/L; reference range, 360 to 1100 U/L), and creatine kinase (528 U/L; reference range, 0 to 300 U/L). A urinalysis revealed 3+ proteinuria with a urine specific gravity of 1.029; however, the urine protein:creatinine ratio was normal.

Ultrasonography revealed a large (8 cm × 4 cm), hypoechoic, heterogeneous mass located between the kidneys and associated with an anomalous, distended caudal vena cava. Color-flow Doppler examination demonstrated marginal blood flow around this mass, suggesting that it was intravascular. The iliac and renal veins were markedly dilated and the caudal vena cava could not be visualized between the kidneys and liver. The hepatic portion of the caudal vena cava and the portal vein were inferred to be normal, as a vena cava was noted in the right cranial part of the liver.

Caudal caval venography, using diatrizoate meglumine (Renograffin-76; Bracco Diagnostics Canada, Mississauga, Ontario) at 740 mg iodine per kilogram body weight (BW), revealed a lack of caudal vena caval opacification between the liver and the 5th lumbar vertebra (L5). Caudal to L5, the vessel was markedly dilated and had a turbulent flow pattern. An amorphous, irregular filling defect, consistent with a large intravascular thrombus, was noted medial to the caudal pole of the right kidney. Extensive collateral circulation was noted in the iliac region, and the right renal and azygos veins were markedly dilated. Central venous pressure was 3 mmHg and caudal vena caval pressure was 19 mmHg.

Magnetic resonance imaging (MRI) was performed in combination with magnetic resonance (MR) venography and angiography. The results confirmed the presence of the blind-ended caudal vena cava at the level of the right kidney and dilated collateral vessels in this region. A moderately heterogeneous, hypointense mass was present in the lumen of the dilated caudal vena cava. Segmental aplasia of the caudal vena cava with secondary thrombus formation was diagnosed.

An exploratory laparotomy was planned to further investigate the obstruction. The preoperative packed cell volume (PCV) was mildly anemic (0.29 L/L; reference range, 0.37 to 0.55 L/L). Given the hypoalbuminemia, 1 unit of fresh frozen plasma was given prior to surgery. During the transfusion and the placing of arterial and venous catheters, blood began to ooze from the sites of catheter insertion and ecchymoses were noted on the thorax. Blood collected for an emergency CBC count revealed anemia (PCV, 0.16 L/L). Platelet estimate was decreased and PT was prolonged (> 60 s). Fibrin degradation products were not elevated and the PTT was distorted due to formation of an abnormal semisolid clot. Disseminated intravascular coagulation (DIC) was suspected and treatment with 1 unit of fresh whole blood and heparin (Wyeth-Ayerst Canada, Toronto, Ontario) at 20 IU/kg BW, SC, q8h, was initiated. Follow-up blood analyses 24 h later showed resolution of the anemia (PCV, 0.37 L/L) and normal estimated platelet numbers; therefore, heparin therapy was discontinued. Forty-eight hours later, PT and PTT were normal.

Two days later, an exploratory laparotomy revealed that the caudal vena cava terminated in a blind ended dilatation (4 cm × 7 cm), just proximal to the kidneys (Figure 1). The vessel could not be identified cranial to this dilatation or caudal to the liver. The left renal and phrenicoabdominal veins were enlarged.

Figure 1. Line drawing of caval aplasia with azygos continuation as seen in this dog.

Distal to the dilatation and the thrombus, the caudal vena cava and renal veins were occluded with Romel tourniquets. Satinsky clamps were placed along the dilated vena cava and stay sutures were placed in the vessel. Venotomy was performed between the stay sutures, the Satinsky clamps were removed and multiple, varying-sized (3 mm to 4 cm), red-brown masses were removed from the vessel. Some of the masses appeared to be soft with an irregular contour, others were firm and friable. Clamps were reapplied and the vena caval incision was sutured in 2 layers with 4-0 polypropylene (Prolene; Ethicon, Peterborough, Ontario) in a simple continuous suture pattern. The abdomen was lavaged with saline and closed in a routine manner. During this procedure, greater than 30% of the dog's total blood volume was lost, necessitating a whole blood transfusion. Pain control was achieved with oxymorphone (DuPont Pharma, Mississauga, Ontario) at 0.1 mg/kg BW, SC. Aspirin therapy (Acetylsalicylic acid; Stanley Pharmaceuticals, North Vancouver, British Columbia) was initiated at 2 mg/kg BW, PO, q24h, to inhibit platelet aggregation; this was continued throughout the first postoperative period. Postoperative ultrasonography revealed that the diameters of the caudal vena cava and iliac veins were decreased, but that a thrombus remained at the blind end of the caudal vena cava. Recovery from surgery was uneventful, with resolution of the ascites. A CBC count was normal and serum biochemical analysis showed resolution of the azotemia.

One month later, the dog was normal on physical examination. Ultrasonography showed a static thrombus. The caudal caval, iliac, and renal veins were enlarged but decreased in magnitude from previous ultrasonograms. Over the subsequent 15 mo, the dog was bright, alert, responsive, and normal on physical examination. However, the owners noted intermittent signs of exercise intolerance and lethargy. Venograms and ultrasonography revealed progressive development of existing collateral circulation. The size of the thrombus increased slowly, measuring 5.4 cm in length by 2.3 cm in width, with extension towards the left renal vein. Sixteen months after surgery, the dog began to experience more episodes of exercise intolerance and mild azotemia (creatinine, 205 μmol/L; urea, 8.8 mmol/L) was apparent on laboratory analysis. Ultrasonography revealed enlargement of the caudal vena cava with thrombus extension into the left renal vein and encroachment towards the right renal vein. Color flow Doppler confirmed flow in both renal veins and in the caudal vena cava proximal to and around the thrombus. A bypass vessel extended between the blind end of the caudal vena cava and the azygos vein.

Due to thrombus encroachment on the renal veins and development of azotemia, a thrombectomy and vena caval reduction was performed. Intraoperative ultrasonography verified the location of the thrombus (Figure 2). Romel tourniquets were placed around the vena cava caudal to the dilatation, and around the right and left renal veins. A 4 cm incision was made in the caudal vena cava and a “V” shaped, friable thrombus (6 cm × 4 cm) was removed. The blind end of the caudal vena cava was partially excised to form a “funnel” into the azygos shunt. The vena cava was closed with a continuous horizontal mattress suture and a simple continuous oversew using 4-0 polypropylene (Prolene; Ethicon). Postoperative ultrasonography and angiography confirmed no visible remaining thrombi and laminar flow in the caudal vena cava. Recovery from the surgery was uneventful and aspirin therapy was continued at 2 mg/kg BW every other day.

Figure 2. Ultrasonic images of thrombus in caudal vena cava, encroaching on renal veins.

Physical examination 6 mo later was normal, and the owner reported resolution of the exercise intolerance. Ultrasonography revealed mildly turbulent flow through the shunting vessel, with no evidence of thrombus recurrence. Annual examinations and continuation of aspirin was recommended.

Towards the heart, the caudal vena cava is divided into 5 segments: prerenal, renal, prehepatic, hepatic, and posthepatic. Developmentally the caudal vena cava and azygos vein emerge through selective anastomoses, persistence, and degeneration of 3 embryologic vessels (1); these include the supracardinal, subcardinal, and vitelline veins. Failure involving these embryologic processes can interrupt the communication between the 5 segments of the caudal vena cava. A plausible embryologic disruption in this case prevented the formation of the prehepatic vena cava. The embryo probably retained one of these earlier vascular connections (middle portion of the supracardinal vein) leading into the future azygos vein in order to return venous blood to the heart (Figure 3).

Figure 3. Development of the caudal vena cava from embryologic vessels.

Abdominal vascular malformations are uncommon in dogs (1,2,3,4,5,6,7,8,9,10,11,12) and humans (8,13). Most are incidental findings at postmortem examination. The most commonly reported vascular anomaly is the portosystemic shunt (1,8). Azygos continuation of the caudal vena cava, as in this case, has been reported (2,3), but it is a rare finding, especially when diagnosed antemortem. Other types of caval malformations include azygos continuation of the caudal vena cava in association with portoazygos shunts (2,10), cor triatrium dexter (abnormal membrane obstructing the caudal vena cava at the level of the right atrium) (4,8,14), and double branching of the caudal vena cava (1,8). Segmental aplasia of the prehepatic portion of the caudal vena cava with azygos continuation and an associated septic thrombus were incidental findings during unsuccessful treatment of a dog with pyometra (2).

The exercise intolerance and ascites seen in this dog is explained by decreased venous return and increased hydrostatic pressure caudal to the thrombus. Fluid dynamics are determined by a combination of intravascular hydrostatic pressure, plasma colloid oncotic pressure, and lymphatic drainage (15). The elevation of caudal caval pressure to 19 mmHg at the time of initial presentation favored the movement of fluid from the vascular compartment into the peritoneal space, resulting in ascites. Clinical signs of exercise intolerance, although improved, persisted in this dog after initial surgery. The remaining thrombus likely caused a partial obstruction to blood flow through the shunt leading from the caudal vena cava into the azygos vein. Venous return to the heart, although adequate during rest, was likely compromised to a greater extent as blood flow to the hind limbs increased during activity.

The mild azotemia seen in this case was likely prerenal in origin, due to partial obstruction of renal venous drainage, renal congestion, and decreased renal perfusion. Resolution of azotemia was documented after both surgical procedures, indicating a return of adequate renal perfusion and an absence of clinically significant permanent renal impairment. Adequate renal function is further supported by a continued ability to concentrate urine. The tentative diagnosis of DIC in this case was based on the presence of cutaneous ecchymoses, a tendency to bleed during venipuncture, an acute drop in PCV, an estimate of decreased platelet numbers, and an increase in PTT (15). A fulminant form of DIC could have occurred following acute decompensation of a chronic, silent process (15). Fibrin degradation products were not elevated, although this does not preclude a diagnosis of DIC (15). It is interesting that all coagulation studies were normal at the time of initial presentation. It is possible that multiple diagnostic procedures, particularly invasive venography, could have caused further endothelial injury at the site of the thrombus that triggered a systemic coagulopathy. Alternatively, manipulation of the thrombus during physical examination and subsequent diagnostic procedures could have caused thromboembolic showering, leading to the development of DIC. It is possible that these findings did not represent DIC at all but were due to anemia from hemorrhage subsequent to venography and splenic platelet sequestration. Hemodilution secondary to rate of fluid administration during surgery may also have contributed to the drop in PCV.

The “masses” removed in both surgeries were histologically identified as recanalizing thrombi. Recanalization and proliferation of endothelial cells indicates chronicity. With time, turbulent blood flow and blood stasis likely caused a slow dilation of the blind end of the caudal vena cava. Chronic turbulence probably resulted in progressive endothelial injury at this site initiating thrombus formation. Reduction of the size of the terminal caudal vena cava during the second surgery was performed to reduce the severity of turbulence and improve laminar flow through the shunt vessel to the azygos vein. Ultrasonography supports the improvement expected with this procedure.

Various thrombolytic agents, such as streptokinase and tissue plasminogen activator, are available but their efficacy against chronic thrombi is controversial. They can potentiate hemorrhage, cause antigenic side effects, and are expensive (16). Without changing the pattern of blood flow, there was no guarantee against thrombi recurrence; therefore, surgical treatment was chosen. Therapies to prevent recurrent thrombi after surgery include heparin, warfarin, and aspirin. Aspirin at 2 mg/kg BW every other day works to prevent platelet aggregation, with minimal risk of secondary gastrointestinal ulceration that often occurs at high doses (15). Heparin is a cofactor for antithrombin III, and, therefore, prevents activation of coagulation (15). Heparin is useful for the acute management of thromboembolism but is not suitable for chronic administration. Coumarin derivatives are indicated for chronic therapy of recurrent thromboembolism but must be used cautiously in animals, as they can cause excessive bleeding (15). Regular monitoring of coagulation times is mandatory in animals during coumarin therapy. To the authors' knowledge, this is the only reported example of segmental aplasia of the caudal vena cava that has undergone treatment and survived. It is likely that many caval anomalies go unnoticed as the animals are asymptomatic. Clinical signs in this dog were not caused directly by the caval anomaly but, rather, were secondary to the effects of thrombus formation. It is challenging to predict the long-term prognosis in this dog, although the improved laminar flow through the shunt, combined with life-long low-dose aspirin therapy, will hopefully preclude recurrence.