Thrombosis Of The Pulmonary Artery In A Yearling Thoroughbred Colt

A 1-year-old thoroughbred colt was examined at the University Veterinary Hospital (University College Dublin) for pyrexia of unknown origin. The colt had a 6-week history of recurrent fever (38.9–40.6 °C), weight loss, and intermittent shifting lameness that had involved various limbs before presentation at the hospital. Two weeks before referral, a blood sample taken by the referring veterinarian had disclosed anemia and leukocytosis, and serum had tested negative for equine infectious anemia with an ELISA test. No improvement in clinical signs had been noted after treatment with neomycin penicillin (IM) and enrofloxacin (IV) of unknown dose and duration. Some resolution in clinical signs after therapy by procaine penicillin (IM), gentamicin (IV), and phenylbutazone (PO) of unknown dose and duration was seen, but clinical signs later worsened and the colt was referred for additional evaluation and treatment. Upon examination, the animal was in poor body condition (body condition score, 3/9)1 and appeared depressed. The colt's rectal temperature (38.3 °C) and respiratory rate (14 breaths/min) were within the normal range and moderate tachycardia (60 beats/min) was present. No cardiac murmurs or arrhythmias were detected upon auscultation and lung sounds were normal during a rebreathing examination. A large painful soft tissue swelling was noted over the right carpus. No other clinically relevant abnormalities were detected on physical examination. Hematologic examination identified mild anemia (packed cell volume [PCV], 28%; reference range, 36–52%; red blood cells, 7.65 × 106/μL; reference range, 7–11 × 106/μL; hemoglobin, 9.1 g/dL; reference range, 13.8–19.4 g/dL), leukocytosis (34,500/μL; reference range, 5,500/μL–9,200/μL) with neutrophilia (27,260/μL; reference range, 2,000/μL–6,000/μL) and left shift (band neutrophils, 3,450/μL; reference range, 0/μL–100/μL), monocytosis (1,040/μL; reference range, 0/μL–500/μL), and hyperfibrinogenemia (700 mg/dL; reference range, 100–400 mg/dL). Serum biochemistry revealed hyperproteinemia (9.8 g/dL; reference range, 5.7–7.9 g/dL) with hyperglobulinemia (7.4 g/dL; reference range, 2.4–4.8 g/dL), and hypoalbuminemia (2.4 g/dL; reference range, 2.9–3.7 g/dL), decreased albumin to globulin ratio (0.32; reference range, 0.62–1.462), decreased serum creatinine concentration (94 μmol/L; reference range, 100–170 μmol/L) and increased alkaline phosphatase activity (358 IU/L; reference range, 0–100 IU/L). Based on the history, physical examination, and laboratory findings, differential diagnoses for fever of unknown origin included a source of persistent infection or inflammation, such as an upper respiratory tract infection (eg, guttural pouch empyema, sinusitis, pharyngeal abscess), lower respiratory tract disease (eg, bronchopneumonia, pleuropneumonia, abscess, neoplasia), abdominal disease (eg, peritonitis, abscess, neoplasia), bacterial endocarditis, piroplasmosis, and diseases currently not reported in Ireland including equine viral arteritis (EVA), anaplasmosis, and leishmaniasis. Respiratory tract disease was considered unlikely given the absence of clinical signs and normal rebreathing examination. Findings of a rectal examination, upper airway endoscopy including examination of the guttural pouches and abdominal ultrasonography all were unremarkable. Radiographs of the swollen right carpal region confirmed a soft tissue swelling and cytological analysis of synovial fluid identified mild, nondegenerative neutrophilic inflammation with an increased white blood cell count (7,800/μL; reference range, 200–900/μL) and increased total protein concentration (5.8 g/dL; reference range, 0.8–2.2 g/dL). No bacteria were observed in or cultured from the synovial fluid. The cytologic changes and culture results were considered suggestive of immune-mediated synovitis. No serum antibodies to EVA were detectable and whole blood polymerase chain reaction was negative for piroplasmosis, anaplasmosis, and leishmaniasis. Echocardiography, performed because of the possibility of bacterial endocarditis, disclosed a 7.53-cm-long, 2.97-cm-wide, sharply marginated, irregularly shaped echogenic mass within the pulmonary artery. On the right parasternal short-axis view, the mass was located about 2–3 cm distal to the pulmonic valve and extended almost to the level of the pulmonary artery bifurcation. The base of the mass appeared to be widely adhered to the arterial wall, whereas the main body extended toward the lumen, occupying almost the entire diameter of the pulmonary artery (Fig 1). The mass also was visible in the right parasternal long axis left ventricular outflow tract view, where it measured 3.41 cm in diameter (Fig 2). From the left parasternal short-axis view, the outline of the luminal part of the mass had a curved shape directed toward the right ventricle and a smoothly rounded tip. Differential diagnoses for the mass based on its ultrasonographic appearance included a thrombus and neoplasia. Right parasternal short-axis view showing the large base (arrows) of the thrombus adhered to the pulmonary artery (PA) wall and the protrusion of the thrombus (arrow heads) into the arterial lumen. AO, aorta; RV, right ventricle. Right parasternal long axis view of the left ventricular outflow tract, showing the pulmonary artery (PA) in cross section. The lumen of the pulmonary artery is almost completely occluded by the echogenic thrombus (arrow head). AO, aorta; LV, left ventricle; RV, right ventricle; RA, right atrium. Despite no abnormalities on the rebreathing examination, thoracic radiographs were performed due to the possibility of pulmonary emboli seeding from the mass in the pulmonary artery. A widespread, moderate to severe interstitial pattern was evident throughout the dorso-caudal lung field, with scattered areas of alveolar infiltration suggestive of embolic bronchopneumonia. On ultrasonography of the thorax, a small amount of anechoic-free fluid was present cranio ventrally within the right pleural cavity and irregularity of the visceral pleura was observed at this level. A percutaneous transtracheal wash was performed and cytological examination showed marked septic, suppurative inflammation; Streptococcus bovis, Aspergillus fumigatus, and Actinobacillus equuli were isolated on bacterial culture. S. bovis was considered a commensal organism and A. fumigatus a contaminant, but isolation of A. equuli was considered clinically relevant. A presumptive diagnosis of infectious pulmonary arterial thrombosis with secondary embolic bronchopneumonia and immune-mediated synovitis was made. A single blood culture, taken 72 hours after antibiotic treatment had been stopped, failed to grow any organisms. After blood for culture had been taken, treatment was started with gentamicina (6.6 mg/kg IV q24h) and sodium penicillinb (22,000 IU/kg IV q6h), as indicated by the sensitivity pattern of the bacteria isolated from the transtracheal wash. The colt also was treated with flunixin megluminec (0.55 mg/kg IV q24h), omeprazoled (4 mg/kg PO q24h), and aspirine (10 mg/kg PO q48h). The initial response to therapy was good with a moderate improvement in the animal's demeanor, and resolution of the swelling over the right carpus. Over the next 14 days, intermittent episodes of lethargy associated with pyrexia were noted. The frequency of treatment with flunixin meglumine was increased (0.55 mg/kg IV q12h) and resulted in maintenance of a normal rectal temperature. The colt remained consistently tachycardic (heart rate, 48–64 beats/min) and developed intermittent, nonpainful swellings of the distal hind limbs that were managed using cold hosing and pressure bandages. Hematologic and biochemical analyses were repeated 14 days after starting treatment and indicated exacerbation of the anemia (PCV, 26%; red blood cells, 6.93 × 106/μL; hemoglobin, 8.3 g/dL), but improvement in the severity of the leukocytosis (12,500/μL), neutrophilia (7,550/μL), left shift (band neutrophils 0/μL), and monocytosis (680/μL). Improvements also were seen in the concentrations of fibrinogen (500 mg/dL), total protein (9.2 g/dL), albumin (2.5 g/dL), globulin (6.7 g/dL), serum creatinine (100 μmol/L), and alkaline phosphatase activity (276 IU/L). Thoracic radiographs were repeated 14 days after the start of treatment, and the interstitial pattern appeared less severe in the most peripheral parts of the dorso-caudal lung field. The alveolar pattern still was present caudal to the perihilar region and appeared more opaque, suggesting lung tissue consolidation. Echocardiography repeated at this time showed no major changes in the appearance or size of the mass within pulmonary artery. Treatment was continued (as outlined above) for another 16 days, and daily urine samples to monitor for gentamicin toxicity were negative for the presence of casts. Hematology performed on Day 24 of treatment showed increasing leukocytosis (20,000/μL), neutrophilia (12,460/μL), and a left shift (band neutrophils, 1,410/μL). Echocardiography repeated 29 days after the start of treatment indicated that the pulmonary artery mass was decreased to 3.38 cm in length. However, based on the overall poor response to treatment, poor prognosis, and financial constraints of the owner, the yearling was humanely euthanized. Postmortem examination confirmed the diagnosis of pulmonary artery thrombosis with diffuse embolic pneumonia. Evaluation of the external surface of the heart disclosed mild dilatation of the right outflow tract. Approximately 3 cm distal to the pulmonic valve, an irregularly shaped soft thrombus was observed (Fig 3), and it extended approximately 3 cm into the pulmonary artery where it was diffusely adherent to the wall. The thrombus protruded approximately 0.5 cm into the lumen. A second thrombus was located over the pulmonary artery bifurcation where it almost obliterated the lumen of the artery leading into the right lung. All cardiac valves appeared grossly normal. Examination of the lungs indicated diffuse, multifocal regions of lung consolidation with central exudate-filled regions following the contours of blood vessels (Fig 4). Microscopic examination of the thrombus and affected lung parenchyma after both hematoxylin and eosin and Gram staining did not identify any bacterial colonies, and no bacteria were cultured from either tissue. The capsule of the right carpal joint was thickened and contained an excessive volume of fluid. Examination of synovial tissue disclosed mild edema and a low-grade mononuclear infiltration. Photograph showing the pulmonary artery thrombus (arrowhead) approximately 3 cm from the pulmonary valve (arrow). Cross section of lung tissue revealing large areas of consolidation (arrowheads) with central foci of necrosis. Thrombosis of a major artery is an uncommon condition in the horse, but has been reported to occur at various sites including the brachial artery,3 femoral artery,4 cranial mesenteric artery5 and terminal aorta and iliac arteries.4,6 Thrombus formation in the main pulmonary artery and its major branches is an uncommon problem in veterinary medicine but has been reported in the dog,7 cat,8 and cow9 and has been associated with various underlying cardiac conditions including hypertrophic cardiomyopathy8 and patent ductus arteriosis9 as well as noncardiac conditions such as glomerulonephritis.7 Pulmonary artery thrombosis also is a rare condition in humans and is almost always associated with endocarditis of the pulmonary valve, but vegetations of the pulmonary artery also have been reported.10 Partial obstruction of the pulmonary artery by a thrombus that had its origin from the pulmonic valve leaflets has been reported previously in the horse,11 and mural thrombi of the right atrium and pulmonary artery have been reported in a horse with systemic blastomycosis.12 To the authors's knowledge, thrombosis of the main pulmonary artery and pulmonary artery bifurcation in the absence of any other cardiac abnormalities has not been reported previously in the horse. The presenting clinical signs and clinicopathological changes in this case suggested a focus of chronic inflammation. Horses presented with clinical signs suggesting a focus of persistent infection or inflammation warrant thorough diagnostic investigation to locate the source. A major differential diagnosis for the clinical signs and clinicopathological changes observed is bacterial endocarditis.13 In these cases, a murmur usually is audible,13 but cases have been described in which a murmur was not detectable despite valvular involvement.13,14 Echocardiography should be performed in cases of suspected bacterial endocarditis to examine the cardiac valves for vegetative lesions even if a cardiac murmur is not present.13 The case reported here further highlights the necessity for detailed examination of the cardiovascular system including ultrasound examination of the pulmonary artery in horses presenting with clinical signs suggestive of bacterial endocarditis in the absence of a cardiac murmur. Echocardiography is a commonly used tool for the diagnosis of bacterial endocarditis11,13,14 and has been shown to correlate well with postmortem findings.13 In this case, the ultrasonographic location of the thrombus 3 cm distal to the pulmonic valve correlated well with the postmortem findings, but the thrombus located over the pulmonary artery bifurcation was visualized only at postmortem examination. Although the pulmonary artery bifurcation normally can be imaged in neonates and older foals, it is only occasionally imaged in normal adult horses.15 Consequently, echocardiography is limited in the diagnosis of thrombosis of the pulmonary artery bifurcation in older horses as illustrated by the current case. A more sensitive diagnostic tool would be computed tomography, which has successfully been used to diagnose thrombosis of the central pulmonary artery in humans,16 but computed tomography for visualization of structures in the thorax of the adult horse currently is not feasible. In the reported case, serial echocardiography was useful in monitoring response to treatment as has been previously described for cases of bacterial endocarditis.13,17 Right-sided endocarditis is likely to produce pulmonary thromboembolism in humans18 and also has been suspected as a cause of pulmonary thromboembolism in the horse.11 In the current case, it was considered likely that the infectious agent involved in the embolic pneumonia was the same as that involved in the pulmonary artery thrombus, therefore antibiotic treatment was guided by the sensitivity pattern of A. equuli isolated from the transtracheal wash. A. equuli species are commensals of the intestinal tract and oral cavity in the horse19, and although opportunistic infections in adult horses are uncommon, endocarditis,20 bronchopneumonia,21 and peritonitis22 secondary to A. equuli infection are among the conditions that have been described. Because of the financial constraints, only a single blood culture was taken in this case, but it is recommended to perform blood culture 2–3 times before the initiation of antimicrobial therapy in cases of bacterial endocarditis.23 In the current case, a similar approach may have resulted in isolation of a different organism allowing for more directed antimicrobial therapy. Poor response to treatment in this case may have been due to inappropriate antimicrobial selection or an inappropriate dose. It has been recommended that horses with bacterial endocarditis be treated at dosages sufficient to achieve serum concentrations of at least 4 times the minimum inhibitory concentration for a specific organism23 and such an approach may have been warranted in this case. Nonetheless, postmortem results did not detect bacteria within the thrombus or lung tissue, which suggests effective sterilization of the lesions. Alternatively, absence of bacteria may have been due to the particular sections of tissue examined histologically or lack of bacterial involvement in the original lesions, but this is unlikely given the horse's clinical signs, clinicopathological abnormalities, and transtracheal wash results. Thrombolytic treatment was instituted in this case using aspirin, as has been recommended for treatment of horses with bacterial endocarditis.23 Treatments with salicylate, heparin, and agents that promote fibrinolysis (streptokinase and plasminogen-activating agents) have been recommended mainly in cats, dogs, and horses with aortic or iliac artery thrombosis, but have a variable success rate.3 Isolated pulmonary artery vegetations have been treated successfully in humans by surgical excision,10 but such an approach is unlikely to be feasible in the horse. Although partial surgical removal of an aorto-iliac thrombus has been described in the horse,24 any attempted surgical treatment of the thrombus in the current case would have been unlikely to affect outcome due to the severity of the embolic pneumonia. Immune-mediated synovitis has been reported previously in horses that have infections at sites other than the joints, and has been attributed to synovial deposition of circulating immune complexes formed as a result of a primary disease process.25 The synovitis in this case most likely was due to a similar pathogenic process, but this would need to be confirmed by immunohistochemical techniques. This report highlights the need to perform an extensive ultrasonographic examination of the heart and great vessels in horses that present with clinical signs and clinicopathological changes supportive of chronic infection or inflammation in order to achieve an antemortem diagnosis. It also illustrates the limitations of echocardiography in diagnosing distal pulmonary artery thrombosis, and alerts the clinician to the possibility of multiple lesions if a thrombus is visualized in the pulmonary artery. aGentaject 10%, Franklin Pharmaceuticals, Trim, Ireland bCrystapen, Schering-Plough Animal Health, Kundl, Austria cFlunixin Injection, Norbrook Laboratories Limited, Newry, Northern Ireland dGastrogard, Merial SAS, Toulouse, France eDisprin, Reckitt Benckiser Healthcare (UK), Hull, UK The authors thank S Warrall, J Brady, M Garrett, and M McCullough for technical assistance and B Cloak for postmortem examination assistance and photography.