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. In order to reproduce the clinical disease experimentally, arterial ligation with the injection of bovine thrombin is required. Thus, it is not primary channel blockade that causes the ischemic 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 to 24 hours after the thromboembolic event that result in the reperfusion injury that kills many cats.

A thrombus develops when blood stasis, endothelial damage and increased coagulation develop. Endothelial damage is present in cats with cardiomyopathy. Furthermore, a fundamental question to answer concerns the vulnerability of cats to thromboembolism.

When the clot dislodges from its site of formation, travels in the arterial system, and decreases blood flow, the clinical consequences of thromboembolism occur. These manifestations are the result of nerve and muscle damage. Ischemic neuromyopathy is characterized by both functional and structural alterations. Although Doppler and perfusion studies can aid in the assessment of the perfusion deficit, only time permits a clear view of the permanent nerve and muscle damage.

The skeletal muscle is more susceptible to ischemic-reperfusion damage than the nerve. Ischemic myopathy affects the cranial tibial muscle to the greatest extent although the gastrocnemius muscle can be severely damaged.

In contrast to the heart and brain, the peripheral nerve is relatively resistant to structural ischemic changes because of the low energy needs, high energy stores, ability to adapt to anaerobic metabolism, and extensive anastomoses.

It is the type and extent of neuropathology that determines the level of recovery of nerve function. Wallerian-type degeneration and paranodal demyelination (affected successive nodes not random as in demyelinating neuropathies) occur.

The physical examination of cats with aortic thromboembolism might include 1) the absence of femoral pulses, 2) firm to hard cranial tibial and gastrocnemius muscles, 3) pale to black cold foot pads, 4) absence of deep pain response, 5) absence of limb motion below the upper thigh, 6) hypothermia, 7) lack of anal tone and distended bladder, 8) abdominal pain if the mesenteric artery also has been embolized, 9) tachypnea and tachycardia (seen with cardiovascular compromise, stress and pain), 10) bradycardia or irregular cardiac rhythm, 11) heart murmur or gallop sound, or 12) varying degrees of depression.

It is in the first few hours that control of pain and anxiety are considered somewhat important. Pain and anxiety increase the sympathetic tone and this is very detrimental to cats with cardiomyopathy. Consequently, treatment with medication that would relieve these symptoms is ideal so long as the price is not excessive sedation and hypotension. In the past, acepromazine has been recommended for such treatment; however, this drug is not recommended. Today butorphanol at 0.2 to 0.4 mg/kg subcutaneously every 4 hours or hydromorphone at 0.05 to 0.1 mg/kg subcutaneously are most frequently used. Butorphanol will not give as much analgesia as the hydromorphone, but the latter is more likely to cause dysphoria. Over-sedation can compromise the ability to judge the status of cardiovascular shock and mentation. Other medications such as fentanyl patches are not recommended because they take too long be effective. This is an important consideration because pain in cats with thromboembolism last a relatively short time of less than 6 to 10 hours.

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 intra-atrial blood stasis or clots. Thoracic radiography permits the determination of pulmonary edema or pleural effusion. Pulmonary edema can exist even if not suspected from the auscultation of the lungs. Moreover, tachypnea is seen in the majority of these cats. The cause can be either pulmonary edema, pain, or both. The radiograph helps to determine if treatment for fluid retention is required.

Serum chemistry abnormalities are common and extensive. Azotemia, hyperglycemia, elevation in muscle enzymes (creatine phosphokinase, aspartate aminotransferase and alanine aminotransferase), hyperkalemia, acidosis, hyperphosphatemia, and hypocalcemia can be documented. Azotemia is usually due to poor perfusion to the kidneys and it is this same mechanism that explains the hyperphosphatemia. Hyperglycemia is hypothesized to be due to two factors: stress and increased lactate. Stress causes an increase in adrenergic hormones that inhibits insulin secretion and this in turn causes the increase in blood glucose. Also contributing to the stress response are high glucagon and cortisol levels. Concomitant with this is that lactate levels are high due to muscle anaerobic glycolysis. Lactate is a major gluconeogenic precursor to cause hyperglycemia. It is believed that insulin resistance is likely not responsible for the hyperglycemia in cats. Elevation in muscle enzymes particularly that of creatine phosphokinase, can be dramatic in cats with thromboembolism due to the muscle necrosis. Poor renal perfusion accounts for the hyperphosphatemia, but again the death of muscle serves as a source for massive quantities of phosphorus. The excessive phosphorus binds to calcium and this accounts for the hypocalcemia. Metabolic acidosis develops in response to the lactic acidosis reaching levels that demand specific treatment. All of these biochemical alterations change over time after the thromboembolic event. The ideal situation is for them to return to normal; however, it is important to particularly watch the potassium concentration as it can increase as reperfusion develops.

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 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. (Figure 5) 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.

For years the use of heparin in acute thromboembosis has been purported in the acute situation. We need to all consider the evidence for this treatment and its value. We actually do not have any evidence of its effectiveness in improving the state of these cats.

Cats will suffer from reperfusion injury to varying degrees depending on the vascular hyperpermeability, hyperkalemia, edema and acidosis present. The aggressiveness in the treatment of hyperkalemia depends on its severity. Treatment can include modest fluid therapy with NaCl (careful to watch for pulmonary edema), intravenous glucose (but if the cat is already hyperglycemic 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 hyperkalemia).

It is clear that these cats need treatment to prevent reembolization which occurs at the rate of about 25% as reported in the most recent reports, but what is uncertain is how this is accomplished. For many decades some have suggested the use of aspirin, while others say it does no good. Studies in th early 1970's showed that experimentally cats treated with aspirin, if thromboembolism did occur, had less severe clinical signs and recovered quicker. But still, thromboembolism occurs. In humans aspirin alone is frequently inadequate to control thromboembolism, whereas, anticoagulation treatment decreases the recurrence. However, treatment with anticoagulants such as Coumadin requires rigorous monitoring that is rarely possible in cats. The LMWH could be an alternative, although when these have been used thromboembolism still developed and the target levels were never obtained at the dose used and the half-life appears short. The latter is problematic because the drug must be administered parenterally and it appears that twice daily administration is inadequate. This type of treatment is likely not practical. Recently, an alternative treatment has been suggested which is antiplatelet rather than anticoagulation.. This drug is clopidogrel (Plavex) and recent studies have shown this to be a safe drug in cats. Clinical trials to determine its effectiveness are required.

In summary, the treatment of thromboembolism in the cat entails multitasking and attention to detail.. An understanding of the pathophysiology will guide us in designing studies to answer the clinical questions. We have made progress in the treatment of this disease, but there is still a long way to go. The fortunate situation is that there are cats that can survive despite our limited knowledge.