Aortic thromboembolism in cats

        © Philip R. Fox, D.V.M., M.Sc.

Thrombotic and thromboembolic complications of feline cardiomyopathy have long been recognized . Thrombosis represents clot formation within a cardiac chamber or vascular lumen. Thrombi can be located in the left atrial cavity (often referred to as "ball" thrombus), left ventricular cavity, or both. Within the LA, thrombus may be found in the body of the LA, in the atrial appendage, or in a combination of these areas. Embolization occurs when a clot or other foreign material lodges within a vessel. The systemic arterial system is almost exclusively involved, as right-sided heart and deep venous thrombosis are rare in cats.

Prevalence

Cardiogenic emboli frequently complicate the course of myocardial disease (such as hypertrophic cardiomyopathy in cats) and result in significant morbidity and mortality. At necropsy, thromboembolism has been reported in up to 48 percent of hypertrophic cardiomyopathy cats, 29 percent of RCM, 25 percent of dilated cardiomyopathy, and 14 percent of cats with excessive left ventricular moderator bands. The prevalence in the general population is undoubtedly less than that detected from necropsy surveys. Clinical studies have reported incidences of arterial thromboembolism ranging from 16-18% in taurine-deficiency dilated cardiomyopathy; 18 percent in idiopathic myocardial failure; 12 percent in HCM ; 13 percent of cats with non-dilated IV hypertrophy; and 19 percent of 46 HCM cats either at clinical presentation or during long-term follow-up. Most cats with systemic arterial thromboembolism have CHF concurrently at the time of clinical embolism. Thromboembolism is uncommon with hyperthyroidism, and a 3 percent incidence of thyrotoxicosis was recorded in 100 cats with saddle embolism.

Age of occurrence for thromboembolism ranged from 1 to 20 years (mean, 7.7 years; median, 10.5 years) in one report. The highest incidence occurred in 4- and 7-year-old cats. A male preponderance was recorded (67 percent). 

The site of cardiogenic embolism is variable, but distal aortic ("saddle") embolization is the predominant clinical location in more than 90 percent of cats affected with thromboembolic complications. The right brachial artery is occasionally occluded (the left brachial artery is only rarely embolized). Left-sided heart mural thrombi are sometimes present, particularly in the left auricle and less often in the left ventricle. Various other organs may become embolized as a consequence of 
systemic embolic "showers," especially the kidneys and, less often, the mesenteric arteries.

Pathophysiology

Pathogenesis of thrombosis requires one or more of three essential conditions to be present: (1) local vessel or tissue injury, (2) circulatory stasis, and (3) altered blood coagulability. Known as Virchow's triad, these prothrombotic factors are invariably present to some degree in myocardial diseases that make cardiomyopathic cats predisposed to thromboembolic events.

      (1) Local tissue injury

Endomyocardial injury is common in all forms of feline cardiomyopathy. Myocardial infarction, endomyocarditis, or aneurysms may occur. More commonly, endothelial fibrosis may be present in the left atrium, left ventricle, or both. Areas of fibrosis may be patchy, focal, or diffuse and are composed of hyaline, fibrous, and granulation tissue with collagenous fibers. Such lesions may present reactive substrates to circulating blood and trigger a thrombotic process by inducing platelet adhesion and aggregation, with subsequent activation of the intrinsic clotting cascade. In addition to fibrillar collagen, exposed thromboplastin or tissue factors may contribute to thrombogenicity. 

(2) Stasis 

Blood stasis predisposes to thrombosis. Cardiac chamber dilation, particularly when associated with reduced contractility, results in large endsystolic volumes and blood stasis. Thrombi are most frequently found in the left atrial appendage in cats regardless of the type of cardiomyopathy, presumably the consequence of poor atrial emptying. Impaired blood flow decreases clearance of activated clotting factors, which sets up clot formation in areas of tissue injury.

(3) Hypercoagulable states

A hypercoagulable environment may be present in some cardiomyopathic cats with thromboembolism. Disseminated intravascular coagulation associated with consumptive coagulopathy, liver-mediated coagulopathy, or thromboembolism was present in more than 75% of affected cats. In addition, feline platelets are very reactive and responsive to adenosine diphosphate (ADP) and other agonists of platelet aggregation. III Serotonin, a vasoactive amine, is released from platelets where it is present in high concentrations in cats and further enhances platelet activation. Others have reported that platelets from cats with cardiomyopathy had increased responsiveness (aggregation) to collagen but decreased responsiveness to ADP. Recently, the influence of hypercoagulable states in human thrombogenesis has become the focus of great interest, and a large menu of tests has emerged to evaluate these disorders. The hypercoagulable states most commonly evaluated in humans at this time include resistance to factor V Leiden (APC), proteins C and S deficiency, antithrombin III (AT III) deficiency, antiphospholipid syndrome, and hyperhomocysteinemia. In a study of 11 cats with cardiomyopathy (7 due to hyperthyroidism), mean AT III activity was increased and AT III behaved as an acute-phase reactant. It is interesting that hyperhomocysteinernia is present in some cardiomyopathic cats with thrombosis (Hohenhaus AE, Simantov R, Fox PR, unpublished data, 1998). These and related conditions must be more fully evaluated in cats with systemic thromboembolism and may play a significant role in their management and prevention.

Role of collateral circulation

Collateral circulation plays a critical role in progression and resolution of clinical thromboembolic disease, and it is modulated by vasoactive substances (e.g., serotonin and others) released by the clot and other substrates. For example, simple distal aortic ligation does not duplicate the clinical syndrome caused by a saddle embolus, whereas experimentally induced aortic thromboembolism simulates the naturally occurring syndrome. Chemicals such as thromboxane A2 also cause vasoconstriction whose synthesis can be reduced by antiprostaglandin drugs such as aspirin.

Pathologic consequences of occlusive ischaemia

The functional integrity of an extremity depends to a large extent on adequate arterial blood supply. Sudden arterial occlusion with almost instantaneous and complete interruption, coupled with decreased- collateral circulation, causes substantial tissue injury. Ischemic neuromyopathy is a predictable consequence of arterial occlusion and, in particular, of clot associated with inhibition of collateral circulation. Ischemia abolishes rapid axoplasmic neuronal flow causing conduction failure, which becomes irreversible after 5 or 6 hours. Distal aortic (saddle) embolization causes peripheral nerve lesions, starting at the mid-thigh region. The majority of nerve fibres display a Wallerian-type of degeneration while some exhibit damage to the myelin sheath only. Clinically, the duration of peripheral nerve function can induce pathologic neuromuscular changes. Focal necrosis, myophagia, and architectural changes may be evident histologically. Distal limbs below the stifle are most severely injured. Cranial tibial muscles are more affected than gastrocnemius muscles, inhibiting hock flexion more than extension. Hip flexion and extension are maintained. The result is a dragging motion of the hind legs. Distal limb sensation is severely affected .


Clinical manifestations

The clinical consequences of arterial thromboembolism depend upon (1) the site of embolization, (2) the severity and duration of occlusion, (3) the degree of functional collateral circulation, and (4) development of serious complications (e.g., hyperkalemia, limb necrosis, self-mutilation). If thromboembolism is suspected, a minimum data base should be generated to include thoracic radiographs, ECG, echocardiogram, biochemical profile, urinalysis, and feline leukaemia virus/feline immunodeficiency (FeLV/FIV) test.

History

Distal arterial embolism characteristically results in peracute clinical signs of lateralizing paresis, vocalization, and pain. Occasionally, intermittent claudication or right front paresis is reported. Signs of CHF are often present concurrently, including dyspnea, tachypnea, anorexia, and syncope.

Physical examination

Clinical signs are attributable to CHF and specific tissues or organs that are embolized (e.g., azotemia from renal infarction, bloody diarrhoea from mesenteric infarction, posterior paresis from saddle embolus). More than 90 percent of affected cats present with a lateralizing posterior paresis caused by a "saddle clot" at the distal aortic trifurcation . Clinical signs are characterized by the four Ps that relate to the extremities: Paralysis, Pain, Pulselesness (lack of palpable femoral arterial pulses), and Polar (cold distal limbs and pads). Cranial tibial and gastrocnemius muscles are often firm or become so from ischemic myopathy by 10 to 12 hours postembolization. In most cases they become softer 24 to 72 hours later. Acutely affected cats can move their back legs by virtue of flexing and extending the hip in a "dragging" manner, but they cannot flex and extend the hock. Invariably, one leg is more severely affected than the other. Nail beds are cyanotic, and distal limbs are commonly swollen. Occasionally, a single brachial artery is embolized, causing monoparesis (usually the right front leg). Intermittent claudication may be observed. In such case arterial pulses may be palpated, foot pads feel warm (normal), and nail beds are not cyanotic. This frequently precedes a more severe thromboembolic event. Less common sites of embolization include renal, mesenteric, pulmonary, coronary, and cerebral arteries. Occlusion of these sites may cause rapidly progressive deterioration and death. Abnormalities detected during thoracic auscultation are common, including heart murmurs, gallop rhythms, pulmonary crackles, or muffled heart and lung sounds. Most affected cats are clinically dehydrated, and many are hypothermic.

Thoracic radiography

Cardiomegaly is usually evident. In most cases biatrial enlargement is present, and the left auricular appendage is often prominent in the ventrodorsal or dorsoventral view. The majority of affected cats have concurrent extracardiac signs of congestive heart failure (e.g., pulmonary edema, pleural effusion), Normal cardiac silhouettes were reported in 11 percent of cats with thromboembolism

Electrocardiography

In one large retrospective study of cats presenting for thromboembolism, 85 percent had ECG changes whereas only 15 percent had no ECG abnormalities. Sinus rhythm was present in 60 percent. Seven percent had supraventricular tachycardia, including atrial fibrillation; 3 percent had ventricular tachycardia; and 28 percent had sinus tachycardia. Isolated supraventricular (19 percent) and ventricular extrasystoles (19 percent) were also recorded .31' As underscored by continuous ECG (Holter) recordings in cats with CHF and systemic thromboembolism, important changes can occur in heart rate and rhythm. Development of atrial standstill and a sinoventricular rhythm indicates hyperkalemia, a catastrophic consequence of reperfusion muscle injury.

Clinical pathology

Most cats have clinical pathology abnormalities. Elevated BUN and creatinine levels were recorded in a little over half of cats at presentation . Mild prerenal azotemia is common since many cats are dehydrated, although renal infarction may play a role in some cases . Serum concentrations of alanine aminotransferase (SGPT) and aspartate aminotransferase (SGOT) are elevated by about 12 hours and peak by 36 hours postembolization, indicating hepatic and skeletal muscle inflammation and necrosis. Lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) enzymes are greatly increased shortly after embolization, indicating widespread cellular injury. Hyperglycaemia, mature leukocytosis, lymphopenia, and hypocalcemia may be present. Acute hyperkalemia can result from reperfusion injury of skeletal muscles downstream from the embolus. Hypokalemia is a common consequence of anorexia and diuretic therapy. Coagulation abnormalities may be detected. Some affected cats have hyperhomocysteinemia (Hohenhaus AE, Simantov R, Fox PR, unpublished data, 1998).

Echocardiography

Echocardiography provides rapid, non-invasive assessment of cardiac structure and function, detects intracardiac thrombi when present, ,and thereby assists in formulating appropriate therapy and prognosis. Multiple imaging planes are required to detect small mural thrombi, particularly in the left auricular appendage. Spontaneous echo contrast ("smoke") may be present in the LA or LV. It is associated with blood stasis and is considered a harbinger and marker for increased thromboembolic risk. The mechanism of smoke has been attributed to erythrocyte aggregation at a low shear rate or platelet aggregates. Left atrial enlargement (LAE) is usually but not invariably present. In a retrospective study of cats with saddle emboli, severe LAE (LA:Ao ratio +/- 2.0) was recorded in 57 percent, moderate LAE (LA:Ao 1.63 to 1.99) in 14 percent, mild LAE (LA:Ao, 1.25 to 1.629) in 22 percent, and 5 percent of cats had normal LA measurements (LA:Ao < 1.25).

Angiocardiography

Non-selective angiocardiography can be considered in the stabilized patient if echocardiography is not available. In this scenario, it can help determine the type of cardiomyopathy and disclose the presence of LA or IV ball thrombi, if any. It is occasionally used to determine the anatomic location or extent of systemic thromboembolism and to assess collateral flow. The technique is relatively simple and requires sedation, jugular venipuncture with a large-gauge (e.g., 19-gauge) needle, hand injection of radiocontrast dye (0.8 to 1.8 mg/kg IV), and rapid, sequential exposure of radiographic cassettes. This technique is not with out risk in decompensated animals. Severe myocardial failure and hemodynamically or electrically unstable arrhythmias constitute relative contraindications.

Differential diagnosis

Differential causes of acute posterior paresis include trauma, intervertebral disc extrusion, spinal lymphosarcoma and other neoplasia, and fibrocartilaginous infarction. Acute front leg monoparesis can be caused by trauma, foreign body, and brachial plexus avulsion. The diagnosis is relatively easy to confirm by physical examination (gallop rhythm; murmur; arrhythmias; cold, pulseless limbs), radiographic and echocardiographic evidence of cardiomegaly and often heart failure, and clinical pathology abnormalities. Thromboembolism uncommonly occurs in the setting of a structurally normal or mildly abnormal heart. Neoplasia is sometimes discovered in the thorax or abdomen (although the mechanistic relationship, if any, is unclear), or systemic inflammation or endocarditis can represent cardiovascular sources of emboli.

Prognosis

Short-term prognosis depends on the nature and responsiveness of the cardiomyopathic disorder and heart failure state. In cases of saddle embolism, motor ability may begin to return in one or both legs within 10 to 14 days. By 3 weeks, significant motor function (i.e., hock extension and flexion) has often returned, typically better in one leg than in the other. Motor function may be completely normal by 4 to 6 weeks, although a conscious proprioceptive deficit or conformational abnormality (e.g., extreme hock flexion) may persist in one leg Unfortunately, most cats experience additional thromboembolic episodes within days to months of the initial event, although survivals of several years, including repeat embolic episodes, have been observed. In one large retrospective study, 34 of 92 cats (37 percent) survived an initial event of saddle embolism. Follow-up 
information was available for 22 of these 34 cats, and an average long-term survival of 11.5 months was recorded .

Thromboembolism is a well-established cause of morbidity and mortality and represents a severe clinical complication. A more favorable prognosis may be suggested by (1) resolution of CHF and/or control of serious arrhythmias, (2) lack of LA/LV thrombi or spontaneous echo contrast, (3) re-establishment of appetite, (4) maintenance of relatively normal BUN/ creatinine and electrolyte levels, (5) return of limb viability and function (e.g., loss of swelling, return of normal limb temperature, return of motor ability), (6) return of femoral arterial pulses and pink nail beds, (7) lack of self-mutilation, and (8) committed owner.

A number of morbid events confer a grave prognosis: (1) refractory CHF or development of malignant arrhythmias, (2) acute hyperkalemia (from reperfusion of injured muscles), (3) declining limb viability (e.g., progressive hardening of the gastrocnemius and anterior tibial muscle group; failure of these muscles to become soft 48 to 72 hours after presentation; development of distal limb necrosis), (4) clinical evidence of multiorgan or multisystemic embolization (e.g., neurologic signs, bloody diarrhea, acute renal failure) which usually accompanies extensive thromboembolism, (5) history of previous embolic episodes, (6) presence or development of LA/LV thrombus or spontaneous echo contrast, (7) rising BUN/creatinine levels, (8) disseminated intravascular coagulation, (9) unresponsive hypothermia, (10) severe LA enlargement with arrhythmia and myocardial failure, and (11) uncommitted owner with limited financial resources,

Therapy

Therapy is directed toward (1) managing concomitant CHF or serious arrhythmias when present, (2) general patient support, including nutritional supplementation, correction of hypothermia, and prevention of self-mutilation, (3) adjunctive therapies to limit thrombus growth or formation, (4) close patient monitoring for limb viability, heart rate and rhythm, progression or regression of CHF, BUN/creatinine and electrolyte levels and appetite, and (5) prevention of repeated events.

Acutely affected cats are a high surgical/anesthesia risk due to CHF, hypothermia, disseminated intravascular coagulation, and arrhythmias Thus, acute embolectomy or surgery is generally contraindicated. Results have been poor, and these procedures have fallen into disfavor.

Various medical. treatments have been proposed, although most are empirical and efficacy is unsubstantiated. The use of acepromazine maleate or hydralazine to encourage arterial vasodilation has been suggested. However, arterial dilation may not be uniform, and flow to muscle beds may not be altered. Moreover, these agents are potentially hypotensive, and they have not been shown to alter platelet-induced reduction of collateral flow caused by vasoactive chemicals such as serotonin.

Limb and/or organ viability is enhanced by rapid resolution of arterial occlusion. Platelets constitute a large component of occlusive arterial emboli. In addition, activated platelets provide a catalytic surface for activation of prothrombin and factor X and may therefore contribute to thrombus initiation, growth, land extension . 

Streptokinase and urokinase act by generating the nonspecific proteolytic enzyme plasmin through conversion of the proenzyme plasminogen. This causes a generalized lytic state, with the incipient hazard of bleeding complications. Streptokinase was studied in a feline model of experimentally induced "aortic embolism. It was administered *as an IV loading dose (90,000 IU/cat over 20 to 30 minutes), followed by a constant-rate infusion (45,000 IU/h) for 3 hours. With this approach, streptokinase predictably produced systemic fibrinolysis with no detectable adverse effects, but it failed to produce significant improvement as measured by venous angiograins, thermal circulatory indexes, or statistically significant reduction in mean thrombus weight. However, a studied clinical evaluation of streptokinase in naturally occurring feline thromboembolism and cardiomyopathy has not been reported.

Tissue plasminogen activator (t-PA) has a lower affinity for circulating plasminogen and does not induce a systemic fibrinolytic state. It binds to fibrin within the thrombus and converts the entrapped plasminogen to plasmin. This initiates a local fibrinolysis with limited systemic proteolysis. Tissue plasminogen (Activase, Genentech) was evaluated in cats with spontaneous thromboembolism. It was administered IV at a rate of 0.25 to 1.0 mg/kg/hr for a total IV dose of I to 10 mg/kg. Successful thrombolysis, defined as evidence of reperfusion within 36 hours of t-PA administration, was reported in 50 percent of the thromboembolic cats; 43 percent of the cats survived therapy and ambulated within 48 hours of presentation. However, 50 percent of the cats died during therapy, which raised major concerns regarding rapid thrombolysis. Complications resulted from hyperkalemia due to reperfusion syndrome (70 percent), heart failure (15 percent), or sudden death (15 percent). Bleeding into and around the kidney was also observed in several cats. Wide-spread clinical interest in this agent has been inhibited by its high cost.

Anticoagulants (heparin, coumarin) have no effects on established thrombi. Their use has been based on the premise that by retarding clotting factor synthesis or accelerating its inactivation, thrombosis from activated blood-clotting pathways can be prevented. In cats who have suffered previous thromboembolism, -or in patients with a predisposition for thrombosis, oral anticoagulant therapy may offer a decreased risk of thromboembolism in exchange for an increased risk of major hemorrhage. It should not be attempted without vigilant monitoring and appropriate patient selection.


Heparin (heparin sodium, Liquaemin) binds to lysine sites on plasma antithrombin 111, enhancing its ability to neutralize thrombin and-activated factors XII, XI, X, and IX; this prevents activation of the coagulation process .42' The efficacy of heparin therapy has been established in many human trials and in experimental animal models for prevention and treatment of venous and pulmonary arterial thrombosis Efficacy in treating cats with spontaneously occurring thromboembolism has never been established, and its use for this indication remains controversial. Reported dosages vary widely. It may be administered at the time of admission as an initial IV dose (100 to 200 IU/kg), then 50 to 100 IU/kg subcutaneously q6-8h."' The dose is then adjusted to prolong activated partial thromboplastin time (APPT) one and a half to two times pretreatment -values. Bleeding is a major complication. Clotting profiles must be closely monitored.

The coumarin drug warfarin (Coumadin Tablets, DuPont) impairs hepatic vitamin K metabolism, a vitamin necessary for synthesis of procoagulants (factors 11 [prothrombin], VII, IX, and X). The initial oral daily dosage (0.25 to 0.5 mg/cat) is adjusted to prolong the prothrombin time (PT) to twice the normal value; alternatively, it is adjusted by the international normalization ratio (INR) to maintain a value of 2.0 to 3.0, as follows:

INR = [Cat prothrombin time ÷ Control prothrombin time]

By this monitoring technique, evaluation of anticoagulant therapy with the PT is adjusted for variations in thromboplastin reagent and laboratory technique. The laboratory should provide an index of sensitivity of the thromboplastin reagent, called an international sensitivity index (ISI). Warfarin and heparin therapies are overlapped for several days in humans because when coumarin treatment is initiated, the level of protein C (a naturally occurring antithrombotic protein) is decreased, creating a thrombogenic potential. Overlapping heparin therapy theoretically counteracts this transient procoagulant effect before other vitamin K-dependent factors (factors 11, IX, and X) are affected by warfarin. The necessity for this manoeuvre in cats has not been established. Warfarin has been proposed by some cardiologists for chronic oral maintenance in cases of advanced myocardial disease. Most advise caution, or reserve it for cases of actual arterial embolism in indoor cats with attentive owners. Cefazolin, Ketoconazole, metronidazole, neomycin, tetracycline, vitamin E, trimethoprim-sulfamethoxazole, and Miconazole can potentially increase the effect of warfarin. Catastrophic haemorrhage is a potential complication of 
coumarin therapy.

Aspirin can be used based upon its theoretical benefit during and after a thromboembolic episode to prevent further embolic events. Aspirin induces a functional defect in platelets by irreversibly inactivating (through acetylation) cyclo-oxygenase, an enzyme critical for converting arachidonic acid to thromboxane A2, and which in the vascular wall is responsible for converting arachidonic acid to prostacyclin . Thromboxane A2 induces platelet activation (through release of platelet adenosine diphosphate) and vasoconstriction (as does serotonin), whereas prostacyclin inhibits platelet aggregation and induces vasodilation . The aspirin-induced acetylation of the cyclo-oxygenase enzyme is irreversible and persists for the life of the platelet, which is 7 to 10 days, as does platelet aggregation and release response to various agonists. In cats, aspirin (25 mg/kg, or 1/4 of a 5-grain tablet q48-72h PO) effectively inhibits platelet function for 3 to 5 days and is relatively safe . Improved collateral circulation has been demonstrated in aspirin-treated cats with experimentally created aortic thrombosis. Concern regarding potential inhibition of prostacyclin by aspirin is not unfounded . The optimal aspirin dose that will inhibit thromboxane A2 production but spare vascular endothelial prostacyclin synthesis has not yet been established for cats. Because the value of aspirin in preventing a first occurrence of cardiogenic emboli is unknown, and its value in preventing thrombus recurrence in cats with previous emboli is doubtful, there is need for clinical trials to assess this therapy. Side effects of aspirin are mainly gastrointestinal and can be severe with overdosage

It appears that the incidence of STE in cats with hypertrophic cardiomyopathy has decreased since the advent of using diltiazem. This may or may not be true. However, calcium channel blockers do have anti-platelet activity in humans, cats, and cattle In addition, diltiazem could have beneficial effects on left atrial hemodynamics. However, subacute oral diltiazem administration did not prevent platelet aggregation in normal cats in one study, whereas aspirin administration did. We believe that diltiazem could still be efficacious in cats with cardiac disease. Consequently, we have considered using thrombolytic agents again, but not with t-PA because it is very expensive.

Amputation

In situations of irreversible loss of limb viability, particularly limb necrosis, amputation provides an alternative to euthanasia when all other patient parameters are stable. In selected cases, good quality of life has been achieved for up to I year post-amputation, although repeated systemic embolization must be anticipated and is a limitation for long- term success. It should be noted that some cats who survive severe saddle embolus incur severe atrophy of their cranial tibial muscle group and sustain permanent flexure of their metatarsus. Such patients, when cared for using a soft, padded protective bandage on the distal limb, may bear weight on the leg and otherwise achieve a good quality of life.

Supportive care

Aspirin is administered for myalgia associated with ischemic myopathy, in addition to anti-platelet effects. Epidural analgesia with morphine (0.05 to 0.1 mg/kg one time) can be safe and effective when administered within the first 12 to 18 hours after embolization. Most affected cats are anorectic, dehydrated, and hypokalemic. It is important to maintain hydration, electrolyte balance, and nutritional support. If CHF has been resolved and the cat remains anorectic, placement of a nasoesophageal feeding tube is advocated for alimentation, particularly during the first week of therapy. Self-mutilation of distal limbs devitalized by an occlusive saddle embolus is commonly exhibited during convalescence and is characterized by excessive licking or
chewing of the toes or lateral hock. Application of a loose-fitting bandage, stockinette, or other barrier is usually effective. Placement of indwelling venous catheters into veins of legs devitalized by occlusive embolus should always be avoided.

Patient monitoring

Clinical pathology evaluations are dictated by patient status. Biochemical profiles are useful to assess renal function and electrolyte status, and coagulation profiles (APTT, partial thromboplastin time [PTT], FSP,-platelet count) are needed to evaluate anticoagulation therapy and detect disseminated intravascular coagulation. Sudden hyperkalemia can result from reperfusion syndrome (ischemic rhabdomyolysis and reperfusion) when arterial blood flow is re-established to a previously ischemic region, resulting in acute catastrophic release of potassium into the systemic circulation, Since this may occur without warning, continuous ECG monitoring of hospitalized cats with thromboembolism is a useful, safe, and cost efficient method to detect large increases in serum potassium concentration. Sequential ECG changes become evident, including P-R interval prolongation and gradual disappearance of P waves, widening of the QRS complex, increasing T-wave amplitude, and bradycardia. Fatal bradyarrhythmias progressing to asystole appear to be the mode of death in these hyperkalemic cats. Standard therapiesfor hyperkalemia may be attempted but have been unrewarding. Aggressive measures to reduce and maintain serum potassium have been successful in a few cases by initial IV administration of sodium bicarbonate, followed by titrated doses of regular insulin and glucose administered by constant-rate infusion.

Prevention

Although aspirin has been demonstrated to exert anti-platelet aggregating properties to feline platelets in vitro, there are no data to support routine prophylactic administration to cats with cardiomyopathy unless countervailing risk factors (see earlier) have been identified. Multi-center clinical trials have not been performed to evaluate preventive strategies.

Effective recommendations for prevention of arterial thromboembolism have not been identified. Anti-thrombotic approaches should be based upon concepts of pathogenesis and an appreciation of relative risks. Large-scale studies are needed to evaluate epidemiology, risk factors, etiopathogenesis, and natural history of cardiomyopathy and systemic embolism. Current data indicate that arterial emboli originate from the heart and therefore represent a cardiac disorder. Cardiomyopathies commonly progress to evolve similar pathophysiologic end-points that favour thrombosis due to a triad of precipitating factors identified by Virchow over a century ago: endothelial injury, a zone of circulatory stasis, and a hypercoagulable state (see Pathophysiology, earlier). Therefore, primary prevention of thromboembolism is basically a battle against the underlying cardiac disorder. No therapies have been identified that reverse or significantly retard the development of feline heart disease or its related pathologic or prothrombotic sequelae. Moreover, it is likely that multiple interactions are involved in thrombogenesis, including myocardial pathology and cardiac dysfunction, platelets, and other blood components and factors.