Thromboembolism is a cardiovascular disease characterized by formation of intravascular embolism (clot).
Thromboembolism is a state in which the hemostatic balance shifts toward excessive platelet activation and fibrin deposition, leading to thrombosis. During thrombotic episodes, dogs can have normo- or hyper-coagulable states.
Initiation of fibrin formation by contact activation requires proteolytic conversion of plasma factor XII to the protease factor XIIa on an endothelial surface. Factor XIIa activates the next zymogen in the coagulation cascade, factor XI, to factor XIa, which in turn converts factor IX to factor IXaβ. This series of reactions, referred to as the intrinsic pathway of coagulation, drives thrombin generation and fibrin formation. However, the importance of the intrinsic pathway, as a whole, to clot formation and stability at a site of injury is probably limited, as factor XII deficiency is not associated with abnormal bleeding.
Predisposing conditions causing hypercoagulability, blood flow stasis, or endothelial injury (e.g. orthopedic surgery, Dirofilaria spp infection) are likely triggers, as well as other mediators, such as neurohumoral factors.
In dogs, thrombus formation is also associated with increased matrix metalloproteinase activities.
Unlike cats, canine thromboembolism is nearly always a secondary phenomenon.
Although thromboembolism may occur anywhere within the cardiovascular system, common predilection sites include the aorta, kidneys and lungs.
Aortic thrombosis in dogs is more likely to involve local thrombosis in the distal aorta with embolization to the arteries of the pelvic limb resulting in chronic progressive ambulatory dysfunction.
A number of underlying disease processes are responsible for this condition including:
- Pulmonary hypertension due to hypertrophic cardiomyopathy, atrial fibrillation, patent ductus arteriosus, ventricular septal defect, premature ventricular complexes and other heart diseases
- Disseminated intravascular coagulation
- Recent administration of corticosteroids, vincristine
- Neoplasia - e.g. osteosarcoma
- Immune-mediated thrombocytopenia, immune-mediated hemolytic anemia
- Chronic renal disease, nephrotic syndrome
- Hypoalbuminemia associated with protein-losing enteropathy
- Heartworm disease as well as post-adulticidal therapy
- Infectious diseases involving bacteremia or viremia
- Iatrogenic - catheter implants
- Iron deficiency
Depending on location of the thrombus, affected dogs present with acute fever, auscultatable murmur, lethargy, hindlimb paresis, dyspnea (due to pulmonary edema and pneumothorax) or lumbar pain (acute nephritis).
Urinalysis usually reveals varying degrees of proteinuria with a urine protein-to-creatinine concentration ratio > 0.5.
A definitive diagnosis usually requires echocardiographic or postmortem examination.
Options for thromboprophylaxis available for clinical use in small animal patients are very limited, with heparin, aspirin and clopidogrel predominating. Chronic warfarin administration is also well-tolerated and appears to be an effective, though costly, short-term and long-term alternative.
New orally-bioavailable anti-factor Xa products such as apixaban, have recently emerged as safe long-term preventatives of thromboembolism in human medicine and may eventually reach the veterinary markets.
Inhibition of matrix metalloproteinases, with drugs such as doxycycline (a nonspecific matrix metalloproteinase inhibitor), may also be an effective therapeutic intervention in the management of acute pulmonary thromboembolism.
The prognosis depends upon degree of cardiopulmonary compromise and patient response to therapy.
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