Tromboembolismo pulmonar en un perro con enfermedad inflamatoria intestinal.
Inflammatory bowel diseases (IBD) are a group of idiopathic disorders characterized by the presence of gastrointestinal clinical signs and histological evidence of intestinal inflammation (Guilford 1996).
The most frequent clinical signs of IBD in the dog are chronic diarrhoea, vomiting, weight loss, anorexia or polyphagia. In human medicine, many extraintestinal signs have been described in the literature; however, in veterinary medicine, they are rarely reported (Guilford 1996a). Polyarthritis (Pedersen et al 1976, Bennet 2005), inflammatory hepatic disease, pancreatitis, nephritis (Weiss et al 1996) and polydipsia (Henderson and Elwood 2003) have been detected in small animals with IBD. Thrombocytopenia and anaemia have also been reported (Ridgway et al 2001, Ristic and Stidworhty 2002). The pathogenesis of these extraintestinal signs is not well understood; immunoregulatory defects have been related with some of these extraintestinal signs (Ridgway et al 2001).
The occurrence of thromboembolisms is a serious complication in human IBD (Talbot et al 1986, Jackson et al 1996). Deep vein thrombosis of the leg and pulmonary emboli are the most frequent events (Talbot et al 1986). The aetiopathogenesis of these complications has been widely discussed, being the presence of hypercoagulable state as the suggested cause for thromboembolism in humans with IBD (Schapira et al 1999).
Here we describe a clinical case of pulmonary thromboembolism in a dog with IBD associated with a protein-losing enteropathy.
A 4-year-old 4-kg sexually intact male Yorkshire Terrier was referred to the Veterinary Medicine Teaching Hospital of the Complutense University of Madrid for a re-evaluation of inflammatory bowel disease.
Two years before, the dog presented with chronic diarrhoea, biliary vomiting, weight loss, and ascites. Blood analysis showed hypoproteinemia (plasma proteins: 3.1 g/dL, albumin: 1.7 g/dL). A histopathological study of endoscopic biopsies had shown a severe lymphocytic-plasmacytic infiltrate in the duodenum, edema in the lamina propria and lymphangiectasia. The dog was initially treated with prednisone (1 mg/kg PO q12 hours for 10 days, 0.5 mg/kg PO q12 hours for 10 days, 0.5 mg/kg PO q24 hours for 10 days, and 0.5 mg/kg PO q48 hours for 60 days), and metronidazole (10 mg/kg PO q12 hours for 21 days). Dietary management using a prescription diet for gastrointestinal disease was administered.
Clinical response after therapy was favourable, obtaining normal values of plasma proteins and albumin after treatment. No medical therapy was administered for two years. Clinical signs were absent for this period of time, until a four-week history of chronic diarrhoea, biliary vomiting, weight loss and ascites was presented. At that time, physical examination revealed some abnormal findings: rectal temperature 36.7[grados]C, slight dehydration (4%), and ascites. Pulse, capillary refill time, and heart and pulmonary sounds were normal. No jugular pulses were detected. Blood analysis showed: PCV: 47%, hemoglobin: 15.5 g/dL, RBC count: 6.85 x [10.sup.6]/[micron]L, platelets: 420 x [10.sup.3]/[micron]L, WBC count: 21.3 x [10.sup.3]/[micron]L, neutrophils: 20.4 x [10.sup.3]/[micron]L, lymphocytes: 0.4 x [10.sup.3]/[micron]L, eosinophils: 0.4 x [10.sup.3]/[micron]L, glucose: 97 mg/dL, urea: 55 mg/dL, creatinine < 0.5 mg/dL, total protein: 2.8 g/dL, albumin: 1.9 g/dL, ALT: 15 IU/L, alkaline phosphatase: 63 IU/L, [Na.sup.+]: 137 mmol/l, [K.sup.+]: 3.7 mmol/l, [Cl.sup.-]: 103 mmol/l, fibrinogen: 116 mg/dL. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were normal; antithrombin III was not evaluated. Serology for Leishmania infantum and Ehrlichia canis was negative. Urine analysis was normal. Protein/creatinine ratio was 0.09 g/mmol. 300 ml of abdominal fluid were removed and analyzed; the specific gravity was of 1.008, total proteins value was 200 mg/dL, 12 nucleated cells/[micron]L were found, and lipids and bacteria were absent. Examination of faeces for parasites was negative. Abdominal ultrasound revealed a significant thickening of the small bowel wall (> 6 mm), though the layered appearance of the bowel wall was maintained.
An upper gastrointestinal endoscopic examination was planned. Metronidazole (10 mg/kg BID) and Hetastarch (20 ml/kg/day IV) were administered for one day prior to the procedure. Pre-anaesthetic electrocardiography was normal. An IV bolus of fentanyl (10 [micron]g/kg) and diazepam (0.2 mg/kg) was administered as pre-anaesthetic. Isoflurane was used for induction (5% MAC) and maintenance (0.5% MAC). The endoscopy revealed erythemic mucosa with a granular appearance and some erosions in the stomach, and erythemic, granular, irregular and friable mucosa in the duodenum. A cardio-respiratory arrest occurred while finishing the endoscopic procedure, and resuscitation manoeuvres were unsuccessful.
Subsequent necropsy revealed a poor body condition, presence of yellowish-fluid in the abdominal cavity, and a severe thickening of the gastric and bowel wall. Some erosions were present in the gastric body and pyloric antrum. Lymphangiectasia was observed in different points of the small bowel (Figure 1). The most important finding in thorax cavity was a thrombosis in the pulmonary artery (Figure 2).
The histopathological study of the endoscopic biopsies revealed a moderate lymphocyticplasmacytic infiltrate in the duodenum, severe oedema in the lamina propria and marked lymphangiectasia. Histopathology of the liver and kidneys didn't show any significant lesion.
[FIGURE 1 OMITTED]
[FIGURE 2 OMITTED]
In human medicine, many extraintestinal manifestations of IBD have been reported, such as musculoeskeletal signs, specially arthritis and ankylosing spondilitis (Rankin 1990, Levine and Lukawski-Travish 1995, Bernstein et al 2001). Other alterations commonly associated to human IBD are ocular signs (iritis/uveitis), hepatobiliary signs (primary sclerosing cholangitis), and cutaneous signs (pyoderma gangrenosum, and erythema nodosum) (Rankin 1990, Levine and Lukawski-Travish 1995, Bernstein et al 2001). Neurological (Lossos et al 1995), respiratory (Mahadeva et al 2000), urinary (Wester et al 2001), cardiac (Hyttinen et al 2003), and pancreatic alterations (Huang and Lichtenstein 2002) have also been described.
Thromboembolic events and other vascular and haematological signs have been described in humans with this disease (Talbot et al 1986, Jackson et al 1997, Novaceck et al 1999). Both Crohn's disease and ulcerative colitis are thought to be associated with a high risk of thromboembolisms (Bernstein et al 2001). In fact, the risk of developing deep venous thrombosis or pulmonary embolism is three times higher in patients with IBD (Bernstein et al 2001). This risk is especially higher in young patients with active disease.
In veterinary medicine, extraintestinal manifestations of IBD are rarely noticed (Guilford 1996). Polyarthritis (Pedersen et al 1976, Bennet 2005), inflammatory hepatic disease, pancreatitis and nephritis (Weiss et al 1996) have been described in small animals. Pruritic concurrent skin diseases have also been reported (Guilford, 1996). These lesions could be due to the immune complex deposition in different organs, secondary to aberrant immunological responses in IBD, though the ethiopathogenesis of these signs is not well understood (Center 1996). Thrombocytopenia and anaemia have also been described in dogs with IBD (Ridgway et al 2001, Ristic and Stidworthy 2002).
In dogs, many diseases lead to prothrombotic tendencies. Diseases that cause endothelial damage, blood stasis or systemic hypercoagulability have a thromboembolic potential (Good and Manning 2003). The common methods used to assess hemostasis are more effective in documenting a trend toward hypocoagulability than one toward hypercoagulability (Good and Manning 2003). Although it is not used commonly in veterinary patients clinically yet, thromboelastography provides a method for identifying hypercoagulable patients (Goggs and others 2009). Hypercoagulability can be due to many factors, including decreased levels of Antithrombin III (ATIII). ATIII deficiency is common in glomerular diseases due to protein loss (DiBartola and Meuten 1980, Greco and Green 1987, Cook and Cowgill 1996, Ritt et al 1997). This deficiency may also occur in diseases causing protein loss through the gastrointestinal tract, like parvoviral enteritis (Otto et al 2000). Protein-losing enteropathies frequently allow the extravasation of larger proteins than in a protein-losing nephropathy. In this case, the haemostatic balance may not be altered because of the simultaneous loss of both large procoagulant factors and small anticoagulant factors in equal amounts (Green 1984). Therefore, protein-losing enteropathies could be less frequently involved with thromboembolic risk (Good and Manning 2003).
This could explain the limited information available in the literature about thrombotic events in dogs with protein-losing enteropathy. Femoral thrombosis has been previously described in a dog with intestinal lymphosarcoma and hypoproteinemia (Ihle et al 1996). Distal aortic thrombosis has also been reported in one case of protein-losing enteropathy (Clare and Kraje 1998). Interestingly, pulmonary thromboembolism was suspected in 2 Yorkshire terriers with protein-losing enteropathy (Kimmel et al 2000). To the author's knowledge, this is the first clinical and pathological description of canine pulmonary thromboembolism associated with IBD.
Diseases most commonly associated with pulmonary thromboembolism in dogs are: heart disease (including heartworm disease), glomerular disease, neoplasia, disseminated intravascular coagulopathy, immune-mediated haemolytic anemia, pancreatitis, sepsis, trauma, hyperadrenocorticism, hypothyroidism, and diabetes mellitus (Burns et al 1981, Klein et al 1989, LaRue and Murtaugh 1990, Corlouer 1994, Kittleson and Kienle 1998, Good and Manning 2003). Prothrombotic tendencies can be exacerbated by immunosuppressive therapy with corticosteroids (Good and Manning 2003).
Pulmonary thromboembolism was not suspected in our case, due to the absence of clinical signs and abnormalities found in the physical examination compatible with this disease. These difficulties have also been described in human medicine. In a recent report, the most frequently underdiagnosed disease in human autopsies (in 61% of cases) was pulmonary thromboembolism (Ermenc 1999).
Taking into account this case report and the incidence of thromboembolic events in human patients with IBD, further studies are required to investigate the rate of thromboembolism or hypercoagulability in dogs with inflammatory bowel disease.
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Garcia-Sancho M., Sainz A., Rodriguez-Franco F., Villaescusa A. and Rodriguez-Bertos A.
Departamento de medicina y Cirugia Animal. Facultad de Veterinaria, UCM. Avenida Puerta de Hierro s/n 28040-Madrid, Spain. Corresponding author: firstname.lastname@example.org
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|Author:||Garcia-Sancho, M.; Sainz, A.; Rodriguez-Franco, F.; Villaescusa, A.; Rodriguez-Bertos, A.|
|Publication:||Revista Complutense de Ciencias Veterinarias|
|Date:||Jul 1, 2010|
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