PATHOPHYSIOLOGY OF ATE
Since the coagulation system plays a large role in ATE, a brief overview of normal hemostasis is needed to understand thrombus
formation, treatment, and, maybe one day, prevention (see the Related Link "Normal hemostasis" below). Once a thrombus forms, it may stay static, grow, or embolize.
Thrombus formation
In general, three conditions favor thrombus formation: blood stasis, hypercoagulability, and endothelial damage. All three
of these conditions, referred to as Virchow's triad, may be present in cats with myocardial disease.
Blood stasis. As the left atrium dilates, blood flow slows. Echocardiographically, this slow velocity appears as spontaneous echo contrast
(SEC). SEC, or "smoke," is a phenomenon that arises from the slowing and sludging of blood, and this slowing results in the
aggregation of red blood cells and other blood components. These clumps of cells and macromolecules often appear as flecks
of echogenic material in the atrium and auricle.
Blood flow velocity in the left auricle can be estimated by using Doppler echocardiography.13 Decreased blood flow velocity in the left auricle has been demonstrated in cats with cardiac disease, and, in one study,
79% of cats with a decreased left auricle velocity had SEC.14
The presence of SEC may be a risk factor for ATE in cats. Several human studies have demonstrated patients with SEC to be
at increased risk for stroke or other embolic events.15 However, no prospective studies in cats have specifically looked at SEC and risk for thromboembolism.
Hypercoagulability. Hypercoagulability has been documented in cats with cardiac disease. In a study that compared normal cats with asymptomatic
cats with HCM, 45% of the cats with HCM had laboratory evidence that suggested hypercoagulability; however, they were not
significantly different from the control group.16
Another study that evaluated only cats with HCM found that 56% and 50% of cats with ATE and SEC, respectively, had evidence
of hypercoagulability.17 That study also provided evidence linking SEC with increased risk of thromboembolism.
Red blood cells and platelets in cats may also be more prone to aggregation than those in other species.18,19
Endothelial damage. Endothelial damage may also play a role in thrombus formation. Endothelial damage has been well-described in people with atrial
fibrillation and predisposes them to thromboembolic events.20 Little information exists on endothelial damage and dysfunction in cats with cardiomyopathy. Endothelial function can be
assessed by measuring circulating levels of biomarkers found in the endothelium such as von Willebrand factor, vascular cell
adhesion molecules, and E-selectin.21 In one study, cats with ATE had significantly higher von Willebrand factor antigen concentrations than did cats with left
atrial enlargement or left atrial enlargement with spontaneous echocardiographic contrast.17 However, that finding may have been a result of endothelial damage due to the thrombus itself.
Embolization
Three potential outcomes exist for a left atrial or auricular thrombus: It could remain static and cause no clinical signs,
it could continue to grow and potentially interfere with the mitral valve orifice, or it could break off (partially or completely)
and travel to distant parts of the body (embolism).8 Cats most commonly present with signs related to thromboembolism. The embolus usually follows the path of least resistance
and lodges at the aortic trifurcation, occluding blood flow to both pelvic limbs. The thromboembolus may be small enough to
only partially occlude one femoral artery, resulting in unilateral signs. Thromboemboli may also lodge in the renal arteries,
resulting in renal failure.
The thrombus occludes the main artery and also impairs collateral circulation. In a study that compared cats that had their
caudal aorta ligated vs. occluded with an experimentally induced thrombus, the ligated cats had only minimal neurologic deficits
and 90% return of blood flow at 72 hours.22 The cats with the thrombus had deterioration of or no change in neurologic signs and had only 23% of preocclusion blood
flow at 72 hours.22
Some factor related to the thrombus itself may inhibit collateral circulation. A likely theory is that the thromboembolus
releases serotonin and thromboxane A2, causing vasoconstriction of the collateral vessels. Cats treated with serotonin and thromboxane antagonists before experimentally
induced aortic thrombus formation had improved collateral circulation compared with the controls.23,24 Treatment with these agents after a thromboembolic event has no apparent benefit in terms of the initial thromboembolus
but may prevent further thrombus formation.8
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