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Feline Arterial Thromboembolism

N. Sydney Moïse, DVM, MS, DACVIM (Cardiology)
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA

Introduction

Thromboembolism occurs most commonly as the result of cardiac disease in the cat with a clot lodged in the distal aorta and iliac arteries. The arterial occlusion alone is not the cause of the reduced circulation, but the effects of the thrombus cause a cascade of vasoconstriction events that reduce collateral circulation. Thus, it is not primary channel blockade that causes the ischaemic neuromyopathy. The cat has many collateral vessels to call upon from the vertebral arterial system, but when this fails to happen the clinical syndrome ensues. Additionally, it is the reopening of these collateral vessels in the 12–24 hours after the thromboembolic event that results in the reperfusion injury that kills many cats.

The skeletal muscle is more susceptible to ischaemic-reperfusion damage than the nerve. Ischaemic myopathy affects the cranial tibial muscle to the greatest extent although the gastrocnemius muscle can be severely damaged. Clinically the muscles become very firm because of a rigor mortis effect. When autolysis occurs the muscle proteins breakdown and the muscles soften at about 36 hours. Also, reperfusion can contribute to the return of the relaxation state, although oedema at this time can contribute to keeping the legs stiff. Focal necrosis, myophagia, internal nuclei, architectural changes and infiltrates are present with some hypertrophic fibres present as compensation from surviving myocytes.

In contrast to the heart and brain, the peripheral nerve is relatively resistant to structural ischaemic changes because of the low energy needs, high energy stores, ability to adapt to anaerobic metabolism and extensive anastomoses. Also, although structural ischaemic changes in the nerve are delayed compared to the muscle, electrophysiological changes can occur early with evoked nerve action potentials and fast axoplasmic flow lost after 30 minutes of complete ischaemia. Nerve fibres may not have ischaemic changes until 5 hours following thromboembolism compared to muscle damage after 2–3 hours. Consequently, some flow needs to return to prevent permanent damage. The insult of ischaemia-reperfusion injury is caused by oxygen free-radicals causing lipid peroxidation and influx of calcium into the cells.

It is the type and extent of neuropathology that determines the level of recovery of nerve function. Wallerian-type degeneration and paranodal demyelination (affecting successive nodes not random as in demyelinating neuropathies) occur. Depending on the severity of the reduction in blood flow, the recovery of limb function that occurs in some cats within a month of the thromboembolism may be due to the repair of the myelin sheath in the demyelinated fibres. Remyelination could occur in this timeframe, whereas effective regeneration would take longer.

Clinical Signs

Thromboembolism may be the first clinical sign of cardiomyopathy in many cats. Clinical signs include both the direct consequences of thromboembolism and the associated cardiac disease: acute hindlimb paralysis, pain, depression or dyspnoea. The majority of cats have both hindlimbs affected, although a single limb (rear or front) can be embolised. Occasionally, a cat may have paresis, rather than paralysis (paraplegia) if affected to a lesser degree. The physical examination of cats with aortic thromboembolism might include:

 Absence of femoral pulses
 Firm to hard cranial tibial and gastrocnemius muscles
 Pale to black cold foot pads
 Absence of deep pain response
 Absence of limb motion below the upper thigh
 Hypothermia
 Lack of anal tone and distended bladder
 Abdominal pain if the mesenteric artery also has been embolised
 Tachypnoea and tachycardia (seen with cardiovascular compromise, stress and pain)
 Bradycardia or irregular cardiac rhythm
 Heart murmur or gallop sound
 Varying degrees of depression

Diagnosis

The diagnostic evaluation of the cat with thromboembolism includes blood pressure, echocardiography, thoracic radiography, serum chemistry and electrocardiography. Although the blood pressure determination in the hindlimbs will not be accurate, an assessment from the forelimbs is important to gauge the overall status of the cat. Echocardiography will reveal the type of cardiomyopathy, the severity of the hypertrophy and/or fibrosis, systolic and diastolic dysfunction, size of the atria, presence of pleural effusion and presence of intra-atrial blood stasis or clots. Thoracic radiography permits the determination of pulmonary oedema or pleural effusion. Pulmonary oedema can exist even if not suspected from the auscultation of the lungs. Moreover, tachypnoea is seen in the majority of these cats. The cause can be either pulmonary oedema, pain or both. The radiograph helps to determine whether treatment for fluid retention is required.

Serum chemistry abnormalities are common and extensive. Azotaemia, hyperglycaemia, elevation in muscle enzymes (creatine phosphokinase, aspartate aminotransferase and alanine aminotransferase), hyperkalaemia, acidosis, hyperphosphataemia and hypocalcaemia can be documented.

Electrocardiography is vital on admission not only for the evaluation of the rhythm, but to ascertain the electrocardiographic evidence of the potassium concentration. Frequently, the electrocardiogram (ECG) on admission is normal, but once reperfusion begins (as early as 6 hours after thromboembolism) the potassium concentrations can elevate quickly. Monitoring of the ECG provides a means to monitor the serum potassium level. Attention should be paid to the P wave, S wave and T wave. Most frequently cats will develop S waves, the P wave flattens and the T wave flips to positive as an indicator that the potassium is increasing. It is vital that the serum potassium be rechecked so that treatment can be started early enough to be of benefit. Severe abnormalities in conduction and rhythm progress as the potassium levels increase.

The initial problems that coexist with thromboembolism are referable to cardiomyopathy and include:

 Respiratory distress because of pulmonary oedema
 Cardiovascular shock

Treatment

Pain and anxiety occur because of the thromboembolism. Tachypnoea and dyspnoea are frequently present and the reason for these signs may not be clear without thoracic radiography to determine the presence or not of coexisting pulmonary oedema. In the ideal situation the thrombus would be removed within 4 hours, but this is not likely to happen because the availability of the procedure is uncommon and it is unknown if cats can survive such surgery. Also, it would be ideal if the clot could be treated immediately with a clot ‘buster’ (e.g., tissue plasminogen activating factor (TPA)) early such that the amount of cell death is decreased to diminish the problems of reperfusion injury. Again, the proper method, drug and talent to offer this treatment are currently lacking in veterinary medicine.

Heparin (unfractionated heparin) is a heterogeneous combination of heparin molecules with disaccharide units of varying lengths. The length of the molecule affects the action. The different size heparin molecules bind in different ways and affect the coagulation to varying degrees. Also, unfractionated heparin has a high affinity to binding with serum protein and cells. Once these are loaded the heparin binds to thrombin (factor IIa) and forms a thrombin-antithrombin complex that is irreversible. Unfractionated heparin inhibits both factor Xa and factor IIa. Inhibition of factor IIa requires the long sugar residues found in unfractionated heparin and these are not found in the low molecular weight heparins (LMWH). It has been suggested that LMWH is better than unfractionated heparin. These heparins are more uniform in their size with fragments of 4–8 kD with an average chain length of 15 subunits and 80% <40 subunits; this is in contrast to the heterogenous mixture of 10–100 subunits for the unfractionated heparin.

Cats will suffer from reperfusion injury to varying degrees depending on the vascular hyperpermeability, hyperkalaemia, oedema and acidosis present. In some, there will be no apparent consequences while in others this is the cause of death. The clinical signs of reperfusion include depression, arrhythmias, conduction disturbances and, in general, ‘crashing’. ECG monitoring permits recognition of changes in serum potassium levels. Additionally, monitoring of the serum potassium levels every 2–4 hours may be required when possible. Knowing when the potassium concentration is increasing and acting on this situation early is key to success. Acidosis will develop in these cats and contribute to the hyperkalaemia. The aggressiveness of the treatment of hyperkalaemia depends on its severity. Treatment can include modest fluid therapy with NaCl (careful to watch for pulmonary oedema), intravenous glucose (but if the cat is already hyperglycaemic this is not effective), sodium bicarbonate (effective for the acidosis too), very low doses of insulin (give with glucose and monitor), to intravenous calcium (directly counteracts the cellular effects of hyperkalaemia).

It is clear that these cats need treatment to prevent reembolisation, which occurs at the rate of about 25%; it is uncertain how this is accomplished. Studies in the early 1970s showed that experimentally cats treated with aspirin, if thromboembolism did occur, had less severe clinical signs and recovered quicker. This type of treatment is probably not practical. An alternative treatment has been suggested which is antiplatelet rather than anticoagulation. This drug is clopidogrel (Plavix) and recent studies have shown this to be a safe drug in cats. A clinical trial is currently underway to determine the best long-term treatment for cats at risk for thromboembolism.

References

1.  Butler HC. An investigation into the relationship of an aortic embolus to posterior paralysis in the cat. Journal of Small Animal Practice 1971; 12(3): 141–158.

2.  Hogan DF, Andrews DA, et al. Antiplatelet effects and pharmacodynamics of clopidogrel in cats. Journal of the American Veterinary Medical Association 2004; 225(9): 1406–1411.

3.  Hogan DF, Andrews DA, et al. Evaluation of antiplatelet effects of ticlopidine in cats. American Journal of Veterinary Research 2004; 65(3): 327–332.

4.  Hogan DF, Ward MP. Effect of clopidogrel on tissue-plasminogen activator-induced in vitro thrombolysis of feline whole blood thrombi. American Journal of Veterinary Research 2004; 65(6): 715–719.

5.  Smith SA, Tobias AH, et al. Arterial thromboembolism in cats: acute crisis in 127 cases (1992–2001) and long-term management with low-dose aspirin in 24 cases. Journal of Veterinary Internal Medicine 2003; 17(1): 73–83.

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