Definition

Aortic thromboembolism results from a thrombus or blood clot that is dislodged within the aorta, causing severe ischemia to the tissues served by that segment of aorta.

Pathophysiology

• ATE is commonly associated with myocardial disease in cats, most commonly hypertrophic cardiomyopathy. It is theorized that abnormal blood flow (stasis) and a hypercoagulable state contribute to the formation of a thrombus within the left atrium. The blood clot is then embolized distally to the aorta. The most common site of embolization is the caudal aortic trifurcation (hind legs). Other less common sites include the front leg, kidneys, gastrointestinal tract, or cerebrum.
• ATE in dogs typically is associated with neoplasia, sepsis, infectious endocarditis, Cushing's disease, protein-losing nephropathy, or other hypercoagulable states. However, in one recent retrospective study, no concurrent condition was identified in 58% of dogs.

Systems Affected

• Cardiovascular-the majority of affected cats have advanced heart disease and left heart failure.
• Nervous/Musculoskeletal-severe ischemia to the muscles and nerves served by the segment of occluded aorta causes variable pain and paresis. Gait abnormalities or paralysis results in the leg or legs involved.

Genetics

Hypertrophic cardiomyopathy, a common associated disease, is likely heritable. Additionally, a family of domestic shorthair cats with remodeled hypertrophic cardiomyopathy who all died of ATE has been reported.

Incidence/Prevalence

• Prevalence is not known in the general population of cats. In two large studies of cats with hypertrophic cardiomyopathy, 12–16% presented with signs of ATE. In two retrospective studies of cats with ATE, 11–25% of cats had previous evidence of heart disease.
• Rare in dogs.

Geographic Distribution

N/A

Signalment

Signs

The presence of the 5 “P's” is helpful to remember the classic clinical signs associated with ATE: Pain, Paralysis or Paresis, Pulselessness, Pallor, and Poikilothermic (cold).

Causes

• Cardiomyopathy (all types)
• Hyperthyroidism
• Neoplasia
• Sepsis (dogs)
• Hyperadrenocorticism (dogs)
• Protein-losing nephropathy (dogs)

Risk Factors

• In the cat, cardiomyopathy is a risk factor. Cardiomyopathic cats with a markedly enlarged left atrium, spontaneous echocardiographic contrast (smoke), or an intracardiac thrombus observed on an echocardiogram are at a higher risk for development of ATE.
• In the dog, hypercoagulable conditions, such as neoplasia, sepsis, endocarditis, protein losing nephropathies, or hyperadrenocorticism are risk factors.

Differential Diagnosis

Hind limb paresis secondary to other causes such as spinal neoplasia, trauma, myelitis, fibrocartilaginous infarction, or intervertebral disc protrusion. These conditions resulting in spinal cord injury present with signs of upper motor neuron disease, whereas ATE patients present with signs of lower motor neuron disease.

CBC/Biochemistry/Urinalysis

• High creatine kinase as a result of muscle injury.
• High aspartate aminotransferase and alanine aminotransferase as a result of muscle and liver injury.
• Hyperglycemia secondary to stress.
• Mild increases in blood urea nitrogen and creatinine due to low cardiac output and possible renal emboli.
• Electrolyte derangements, due to low output and muscle damage, such as hypocalcemia, hyponatremia, hyperphosphatemia and hyperkalemia are not uncommon.
• CBC and urinalysis changes are non-specific.

Other Laboratory Tests

Routinely available coagulation profiles typically do not reveal significant abnormalities because the hypercoagulability results from hyperaggregable platelets. In the dog, thromboelastrography may suggest a hypercoagulable state with a clot strength (increased maximum amplitude) or shortened clotting time (decreased R).

Imaging

Diagnostic Procedures

Pathologic Findings

• Thrombus typically is identified at the caudal aortic trifurcation.
• Occasionally, a left atrial thrombus is seen.
• Emboli of the kidneys, gastrointestinal tract, cerebrum, and other organs also may be seen.

Appropriate Health Care

Initially, cats with ATE should be treated as inpatients because many have concurrent congestive heart failure and require injectable drugs, in addition to being in considerable pain and distress.

Nursing Care

• Fluid therapy is cautiously used as most cats have advanced myocardial disease. If in congestive heart failure, IV fluid therapy may not be necessary.
• Supplemental oxygen therapy or thoracocentesis may be beneficial if in congestive heart failure.
• Initially, minimally handle the affected legs. However, as reperfusion occurs, physical therapy (passive extension and flexion of the legs) may speed full recovery.
• Do not perform venipuncture on the affected legs.
• These animals may have difficulty posturing to urinate and may need to have their bladders expressed to prevent overdistention or urine scald.

Activity

Restrict activity and stress

Diet

Initially, most cats are anorexic. Tempt these cats with any type of diet to keep them eating and avoid hepatic lipidosis.

Client Education

• Short- and long-term prognosis is poor in both dogs and cats.
• Most cats will re-embolize. Most cats that survive an initial episode will be on some type of anticoagulant therapy that may require frequent re-evaluations and an indoor lifestyle.
• Most cats that survive an initial episode will recover complete function to the legs; however, if ischemia was severe and prolonged, sloughing of parts of the distal extremities or persistent neurologic deficits may result. In one study, approximately 15% of cats had permanent neuromucscular abnormalities after surviving the initial embolic event.
• Based on 3 small retrospective studies in dogs, the prognosis is generally poor but may be better in dogs presenting with chronic (vs. acute) lameness and dogs treated appropriately with warfarin.

Surgical Considerations

• Surgical embolectomy typically is not recommended because these patients are high risk for surgery because of severe heart disease.
• Rheolytic thrombectomy has been used with limited success in a small number of cats with ATE.

Drug(s) Of Choice

• Thrombolytic therapy (e.g., tissue plasminogen activator [TPA]) is used extensively in humans and infrequently in cats and dogs. These drugs are expensive and carry a significant risk for bleeding complications; to date, they have not demonstrated improved treatment efficacy and thus are rarely used in general practice. TPA is theorized to be more beneficial if given early, ideally, within the first 6 hours of the event.
• Clopidogrel is an antiplatelet aggregation drug. One may choose to give a loading dose of clopidogrel for treatment of an acute embolic event. The loading dose in the cat is 75 mg/cat PO once and then maintenance dose starting 24h later is 18.75 mg/cat (one-fourth of 75 mg tablet) PO q24h. The loading dose in the dog is approximately 10 mg/kg once and then a maintenance dose of 1 mg/kg q24h. When compared to aspirin, clopidogrel was superior in preventing re-embolization, resulting improved survival times in cats that had survived an ATE.
• Unfractionated heparin is the preferred anticoagulant drug in general practice for initial management of feline ATE. Heparin has no effect on the established clot; however, it prevents further activation of the coagulation cascade. In either a cat or dog, give an initial dose of 100–200 units/kg IV and then 200–300 units/kg SC q8h. Alternatively, heparin can be administered as a CRI, if there is concern about adequate bioavailability via the SC route, at a dose of 25–35 units/kg/h. Titrate the dose to prolong the activated partial thromboplastin time approximately two-fold.
• Aspirin is theoretically beneficial during and after an episode of thromboembolism because of its antiplatelet effects. The dose in cats is an 81 mg tablet PO q48–72h. Vomiting and diarrhea are not uncommon. Some specialists advocate a mini dose of 5 mg/cat q72h. Antithrombotic dose recommendations for dogs range from 0.5 to 2 mg/kg q24h. Always give aspirin with food.
• Buprenorphine in the cat is useful and widely available drug used for analgesia and sedation at a dose of 5–20 µg/kg IV, SC, or in cheek pouch q6–8h. For stronger analgesia, use fentanyl or hydromorphone.
• Acepromazine may be cautiously used for its sedative and vasodilatory properties at a dose of 0.01–0.02 mg SC q8–12h.
• Warfarin, a vitamin K antagonist, is the anticoagulant most widely used in humans and has been proposed for prevention of re-embolization in cats surviving an initial episode. The initial dose is 0.25–0.5 mg/cat PO q24h or 0.05–0.2 mg/kg PO q 24h in the dog. Overlap with heparin therapy for 3 days. The dose is then adjusted to prolong the prothrombin time approximately two times its baseline value or to attain an international normalized ratio of 2 to 3. Long-term management with warfarin can be challenging because of frequent monitoring and dose adjustments in addition to bleeding complications. In one study, dogs treated appropriately with warfarin had a better clinical outcome.
• Low molecular weight heparin has recently been proposed for the long-term prevention of feline ATE. LMWH has a more predictable relationship between dose and response than warfarin and does not need monitoring or dose adjustments. It also has a lower risk of bleeding complication. The main disadvantage of LMWH is high drug cost and the injectable route of administration. The two LMWHs that have been used in feline ATE are: dalteparin (100–150 units/kg SC q8–24h) and enoxaparin (1 mg/kg SC q12–24h). Best dose unknown. LMWH usually started q24h due to cost. Some studies suggest q6h dosing necessary for stable blood levels, but may increase bleeding risk.

Contraindications

N/A

Precautions

• Anticoagulant therapy with heparin, warfarin, or the thrombolytic drugs may cause bleeding complications.
• Avoid a nonselective beta-blocker such as propranolol as it may enhance peripheral vasoconstriction.

Possible Interactions

Warfarin may interact with other drugs, which may enhance its anticoagulant effects.

Alternative Drug(s)

N/A

Patient Monitoring

• ECG monitoring while the cat is in hospital is helpful to detect reperfusion injury and hyperkalemia related ECG changes.
• Monitoring electrolytes and renal parameters periodically may be helpful to optimize management of the cardiac disease.
• Examine the legs frequently to assess clinical response. Initially, APTT should be performed once daily to titrate the heparin dose.
• If warfarin is used, PT or INR is measured approximately 3 days after initiation of therapy and then weekly until the desired anticoagulant effect is reached. Thereafter, measure three to four times yearly or when drug regimen is altered.

Prevention/Avoidance

Because of the high rate of re-embolization, prevention with either clopidogrel, aspirin, warfarin, or LMWH is strongly recommended.

Possible Complications

• Bleeding with the anticoagulant therapy.
• Permanent neurologic deficits or muscular abnormalities in the hind limbs may arise with prolonged ischemia.
• Recurrent congestive heart failure or sudden death.
• Reperfusion injury and death usually associated with hyperkalemic arrhythmias.

Expected Course and Prognosis

• Expected course is days to weeks for full recovery of function to the legs.
• Prognosis, both short term and long term, is poor in cats.
• In two large studies, ∼ 60% of cats were euthanized or died during the initial thromboembolic episode. Long-term prognosis varies between 2 months to several years; however, the average is a few months with treatment. Predictors of poorer prognosis include hypothermia (<99°F) and congestive heart failure. One study demonstrated a median survival time of 77 days in cats with congestive heart failure and 223 days in cats without congestive heart failure. Predictors of better prognosis include normothermia, single leg affected, and presence of motor function on initial exam.
• In dogs, the disease is rare and prognosis in general is also poor. One study suggested a better prognosis if the dog had chronic clinical signs and if treated with warfarin.
• Recurrence of ATE is common.

Associated Conditions

See “Causes” and “Risk Factors”

Age-Related Factors

N/A

Zoonotic Potential

None

Pregnancy/Fertility/Breeding

N/A

Synonyms

• Saddle thromboembolism
• Systemic thromboembolism

See Also

• Cardiomyopathy, Dilated-Cats
• Cardiomyopathy, Hypertrophic-Cats
• Cardiomyopathy, Restrictive-Cats

Abbreviations

• APTT = activated partial thromboplastin time
• ATE = aortic thromboembolism
• CRI = constant rate infusion
• ECG = electrocardiogram
• INR = international normalized ratio
• LMWH = low molecular weight heparin
• PT = prothrombin time

Client Education Handout Available Online