Source: UNIV OF PENNSYLVANIA submitted to NRP
A PROSPECTIVE INVESTIGATION INTO THE PRESENCE AND MECHANISM OF HYPERCOAGULABILITY IN DOGS WITH CHRONIC ENTEROPATHY AND PROTEIN LOSING ENTEROPATHY
Sponsoring Institution
Cooperating Schools of Veterinary Medicine
Project Status
ACTIVE
Funding Source
Reporting Frequency
Annual
Accession No.
0216832
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Jun 8, 2008
Project End Date
Dec 31, 2010
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
UNIV OF PENNSYLVANIA
(N/A)
PHILADELPHIA,PA 19104
Performing Department
SCHOOL OF VETERINARY MEDICINE
Non Technical Summary
Protein losing enteropathy is a severe form of gastrointestinal (GI) disease resulting in severe protein loss through the GI tract. It has many causes and is a fairly common condition in veterinary medicine. Formation of blood clots (which subsequent lodging of clots in various parts of the body) is known to be a life threatening complication of many diseases in both human and veterinary medicine. While protein losing enteropathy has been associated with blood clot formation in humans, this relationship has not been well studied in dogs. Improving our understanding of the relationship between protein losing enteropathies and blood clot formation will help direct our treatment course for dogs at risk and may lead us to initiate prophylactic anticoagulant therapy, thereby decreasing the incidence of thromboembolic disease, morbidity, and mortality. Dogs with chronic GI disease, with and without protein losing enteropathy, will be screened for a tendency to form blood clots using blood tests. These tests will be performed at the time of diagnosis and 3 weeks following the initiation of treatment. We expect that dogs with protein losing enteropathy will be prone to blood clot formation. This information may help guide preventative treatment plans for such patients.
Animal Health Component
(N/A)
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
31138301020100%
Knowledge Area
311 - Animal Diseases;

Subject Of Investigation
3830 - Pets (companion animals);

Field Of Science
1020 - Physiology;
Goals / Objectives
1. To evaluate for the presence of a hypercoagulable state in dogs with protein losing enteropathy and chronic enteropathy without excessive protein loss using thromboelastography (TEG). Hypothesis: We hypothesize that dogs with protein losing enteropathy are in a hypercoagulable state and that they are more hypercoagulable that dogs with chronic enteropathy without excessive protein loss. 2. To elucidate the mechanism for hypercoagulability in this population by measuring plasma levels of procoagulant, anticoagulant, fibrinolytic analytes and a panel of inflammatory mediators and cytokines. Hypothesis: We hypothesize that the mechanism of hypercoagulability involves loss of anticoagulant proteins such as antithrombin III and protein C through the diseased gastrointestinal tract. However, the mechanism is likely multifactorial and other imbalances of coagulation and fibrinolysis, along with alterations of inflammatory mediators and cytokines may be involved. 3. To determine if treatment of the underlying disease process affects the hypercoagulable state. Hypothesis: We hypothesize that treatment of the underlying enteropathy (diet change, antiinflammatories, etc) will improve the hypercoagulable state after 3 weeks of therapy. However, treatment with high doses of corticosteroids, when indicated, may worsen the hypercoagulability at this time point. In order to assist in evaluating clinical response, a questionnaire based on clinical signs at home will be provided to clients to assess their pet's response to treatment.
Project Methods
Dogs admitted to the Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania for upper gastrointestinal endoscopy to investigate chronic gastrointestinal clinical signs (any one or more of: vomiting, diarrhea, weight loss, decreased appetite) of > 3 weeks duration will be screened for enrollment into the study. Dogs meeting the patient selection guidelines and inclusion/exclusion criteria will be allocated to one of two groups: protein losing enteropathy (PLE) or chronic enteropathy (CE) based on serum biochemical parameters. All patients enrolled in the study will have the following procedures performed: Visit 1 (up to 2 weeks prior to endoscopy): Coagulation parameters Thromboelastography (TEG), Coagulation profile (aPTT, PT, TCT, Fibrinogen), D-dimers, Fibrinogen, vWF:Ag, Antithrombin, Plasminogen, Protein C Other Cobalamin (vitamin B12), Folate, Homocysteine, Cytokine panel Visit 2 (3 weeks following initiation of therapy) Abbreviated biochemical screen (TP, Alb, Cholesterol, ALP, ALT, Ca) ,TEG, Coagulation profile, D-dimers, Fibrinogen, vWF:Ag, Antithrombin, Plasminogen, Protein C, Cobalamin, Folate, Cytokine panel, Platelet count Owners will also be given a short survey at each visit to determine CCECAI at visit 1 and visit 2.