Therapy Of Thromboembolic Disease

The management of primary diseases resulting in the development of thromboembolism is discussed in related posts throughout this textbook. Therapy of thromboembolism should be directed toward the underlying disorder whenever possible. Therapeutic strategies for managing thromboembolism include short-term systemic anticoagulation and fibrinolysis followed by long-term antiplatelet or anticoagulant therapy to reduce the risk of rethrombosis.

Supportive Care

General patient care is critical for successful management of thrombosis. Analgesic agents should be considered for acute pain management. Fluid therapy should be administered when indicated to correct acid-base abnormalities and dehydration. Dextrose-containing fluids should be avoided whenever possible because they may cause endothelial damage, further promoting thrombosis. A risk of volume overload exists with heart failure or pulmonary hypertension and fluid therapy must be carefully monitored. Strict cage rest and oxygen therapy are indicated in cases of pulmonary thromboembolism or thrombosis associated with congestive heart failure (CHF).

Acute Anticoagulation

Heparin is the mainstay of acute anticoagulation. Anticoagulants prevent additional clots from forming but do not dissolve clots (see thrombolysis). Coumadin therapy for the long-term control of thrombosis is initiated after adequate hepariniza-tion has been achieved.

Heparin functions as a cofactor with antithrombin III, and together this complex exerts its effect by neutralizing factor X and thrombin. Heparin is inactivated by gastrointestinal (GI) enzymes when given orally and therefore must be administered by injection. Heparin is administered to prolong the baseline activated partial thromboplastin time (aPTT) to 1.5 to 3.0 times the baseline value. Prolongation of the aPTT or activated coagulation time (ACT) does not correlate well with heparin levels in cats and dogs, and measurement of plasma heparin levels may be more useful in monitoring heparin therapy. Although many different heparin doses have been advocated, little clinical data exist concerning efficacy. Doses of heparin required to achieve adequate heparin levels in cats with thromboembolism ranged from 175 U/kg every 6 hours to 475 U/kg every 8 hours, subcutaneously. In normal dogs the dose of heparin required to achieve adequate heparin concentrations was 250 U/kg every 6 hours, subcutaneously. The most common side effect of heparin therapy is hemorrhage. In the event of severe hemorrhage, heparin can be neutralized by protamine sulfate administration.

Low molecular weight (LMW) heparin is being increasingly used. Its anticoagulant effect is limited to blocking the activity of factor X. Because LMW heparin has a lower antithrombin effect than unfractionated heparin, LMW heparin does not markedly influence the PT or aPlT. Measurement of factor X activity has been used to assess the effect of LMW heparin. One advantage of LMW heparin is that it has a lower risk of hemorrhage than conventional hep-arin therapy. The optimal dose of LMW heparin in dogs and cats with thromboembolic disease remains to be determined.

Chronic Anticoagulation

Warfarin (Coumadin) is a vitamin K antagonist inhibiting the synthesis of vitamin K-dependent clotting proteins (prothrom-bin and factors VII, IX and X). In addition, warfarin reduces efficacy of the vitamin K-dependent regulatory proteins C and S. Proteins C and S are anticoagulant factors, and their function is the first to be inhibited by warfarin administration. Therefore heparin and warfarin administration are generally overlapped for 2 to 4 days to prevent a transient hypercoagulable state. Some animals appear to do well with just warfarin. Starting doses for warfarin are 0.25 to 0.5 mg every 24 hours in the cat and 0.1 to 0.2 mg/kg every 24 hours in the dog. Due to the high individual patient variability, close monitoring of PT is essential. Early recommendations were to maintain PT 1.5 times the baseline value, and more recent recommendations suggest attaining an international normalized ratio (INR) of 2:3. INR is calculated by the formula (patient PT/control PT). The ISI is a value specific to the tissue thromboplastin that is used in measuring the PT Coumadin is continued on a long-term basis to prevent recurrent TE. Studies documenting the optimal dose, efficacy, and duration of Coumadin therapy for specific thromboembolic diseases in dogs and cats are unknown.

The use of Coumadin is not without risks. The major risk is fatal hemorrhage, which occurs acutely and unexpectedly. Ideally, pets maintained on Coumadin should live indoors and be well supervised to prevent trauma and to monitor for hemorrhage. Periodic measurement of the PT should be done to ensure adequate dosing. Coumadin interacts with many drugs. The addition of medications to the treatment regimen of a pet on Coumadin should be done cautiously because certain drugs will raise the activity of Coumadin and predispose patients to bleeding. Some of these drugs are phenylbutazone, metronidazole, trimethoprim sulfa, and second- and third-generation cephalosporins. Barbiturates will decrease Coumadin anticoagulant effect. If bleeding complications occur, warfarin therapy is discontinued and administration of vitamin K is recommended.

Antiplatelet Therapy

Antiplatelet drugs have been advocated for long-term management to prevent rethrombosis. These drugs inhibit platelet aggregation and adhesion, preventing the formation of the hemostatic platelet plug. Aspirin inhibits cyclooxygenase, leading to decreased thromboxane A2 synthesis. This renders platelets nonfunctional by preventing their aggregation. Cats lack the enzyme needed to metabolize aspirin (glucuronyl transferase), making them sensitive to aspirin-induced platelet dysfunction. Doses of 0.5 mg/kg every 12 hours in the dog and 25 mg/kg twice weekly in the cat may decrease platelet aggregation. However, rethrombosis generally occurs despite aspirin therapy, although it is not known whether aspirin delays recrudescence. Additional antiplatelet drugs include dipyridamole and ticlopidine. Dipyridamole is thought to inhibit platelet aggregation by inhibition of platelet phospho-diesterase, leading to increased levels of cyclic adenosine monophosphate (cAMP) within platelets. Ticlopidine impairs fibrinogen binding and inhibits platelet aggregation induced by ADP and collagen. The use of these newer compounds has been limited thus far in veterinary medicine.


Thrombolytic agents such as streptokinase, urokinase, and tissue plasminogen activator (tPA) are potent activators of fib-rinolysis. These agents have been used with variable and often limited success in veterinary medicine.

Streptokinase binds plasminogen, and the complex transforms other plasminogen molecules into plasm in. Plasmin then binds to fibrin and causes thrombolysis. Streptokinase binds both free and clot-associated plasminogen. It also degrades factors V, VIII, and prothrombin, resulting in a massive systemic coagulation defect.

Streptokinase has been used to treat aortic thromboembolism (ATE) in cats with varying degrees of success. In one study of 46 cats, 15 were discharged from the hospital after streptokinase therapy with a median survival of 51 days. Reperfusion injury occurred in approximately 35% after thrombolysis, with streptokinase often resulting in fatal hyperkalemia and metabolic acidosis- Eleven of the cats developed clinical hemorrhage after streptokinase therapy. In three cats, hemorrhage was significant enough to require transfusion. Others reported conservative management (treatment of heart failure plus Coumadin or aspirin) of thromboembolism with a hospital discharge rate of 28%, which was similar to cats treated with streptokinase. One recommended dose of streptokinase for dogs and cats with thromboembolism is 90,000 U, intravenously administered over 20 to 30 minutes, followed by a maintenance infusion of 45,000 U for 7 to 12 hours. Infusions may be repeated over a total of 3 days.

Recombinant DNA technology produces t-PA, a serine protease. A complex forms between t-PA and fibrin, and that complex preferentially activates thrombus-associated plasminogen-resulting in rapid fibrinolysis. Life-threatening hemorrhage is the number one side effect. The half-life of t-PA in dogs is 2 to 3 minutes; consequendy, if bleeding occurs, stopping the infusion will result in the drug clearance from the system in 5 to 10 minutes. Because t-PA causes rapid thrombolysis, the risk of reperfusion syndrome and lethal hyperkalemia is substantial. In one report, 50% of cats with thromboembolism died acutely during t-PA therapy, with death attributed to hyperkalemia, severe anemia, and renal hemorrhage.



Thoracic Ultrasonography

Thoracic ultrasonography currently is regarded as the preferred method to diagnose pleuropneumonia in the horse. Although the value of the art of thoracic auscultation and percussion should not be undermined, clinicians managing horses with thoracic disease recognize the limitations of these tools. With the widespread use of thoracic ultrasound, the equine practitioner currently has the ability to determine the presence of pleuropneumonia and the location and the extent of the disease. Although sector scanners are superior (preferably 3.5- to 5.0-MHz transducers), linear probes also can be used to evaluate the thorax in practice.

Thoracic ultrasonography in horses with pleuropneumonia allows the clinician to characterize the pleural fluid and to evaluate the severity of the underlying pulmonary disease. The appearance of the pleural fluid may range from anechoic to hypoechoic, depending on the relative cellularity (). This fluid usually is found in the most ventral portion of the thorax and causes compression of normal healthy lung parenchyma with retraction of the lung toward the pulmonary hilus. The larger the volume of the effusion is, the greater the amount of compression atelectasis and lung retraction that occurs.

The presence of adhesions, pleural thickening, pulmonary necrosis, and compression atelectasis also can be detected. Fibrin has a filmy to filamentous or frondlike appearance and is usually hypoechoic (). Fibrin deposited in layers or in weblike filamentous strands on surfaces of the lung, diaphragm, pericardium, and inner thoracic wall limits pleural fluid drainage. Dimpling of the normally smooth pleural surface results in the appearance of “comettail” artifacts, created by small accumulations of exudate, blood, mucus, or edema fluid. Pulmonary consolidation varies from dimpling of the pleural surface to large, wedge-shaped areas of sonolucent lung ().

Atelectatic lung is sonolucent and appears as a wedge of tissue floating in the pleural fluid. Necrotic lung appears gelatinous and lacks architectural integrity. Peripheral lung abscesses are identified ultrasonographically by their cavitated appearance and the absence of any normal pulmonary structures (vessels or bronchi) detected within. Although detection of a pneumothorax may be easy for the experienced ultrasonagrapher, it is not as easy for the less experienced. The gas-fluid interface can be imaged through simultaneous movement in a dorsal to ventral direction with respiration, the “curtain sign” reproducing the movements of the diaphragm. The dorsal air echo moves ventrally during inspiration, similar to the lowering of a curtain, gradually masking the underlying structures. A pneumothorax without pleural effusion is even more difficult to detect ultrasonographically. Although free bright gas echoes within the pleural fluid can occur after thoracentesis, they are more often seen with anaerobic infections or when sufficient necrosis has occurred in a segment of parenchyma to erode into an airway and form a bronchopleural fistula (). The absence of gas echoes in pleural fluid does not rule out the possibility that anaerobic infection may be present.

Ultrasonography is a valuable diagnostic aid in the evaluation of the pleura, lung, and mediastinum of horses with pleuropneumonia. The detection and further characterization of the above abnormalities improve the clinician’s ability to form a more accurate prognosis. Adhesions can be detected that ultimately may affect the horse’s return to its previous performance level.

Horses with compression atelectasis and a nonfibrinous pleuritis have an excellent prognosis for survival and return to performance. The detection of areas of consolidation, pulmonary necrosis, or abscesses increases the probable treatment and recovery time, and the prognosis for survival decreases as these areas become more extensive. Ultrasonography can be used as a guide to sample or drain the area with a large fluid accumulation or the least loculation. These patients often benefit from progressive scanning to assess response to treatment and the need for drainage.

Pleural Drainage

After selection of an appropriate antimicrobial agent, the next decision to be made is whether to drain the pleural space. Ideally the decision is based on an examination of the pleural fluid. If the pleural fluid is thick pus, drainage using a chest tube should be initiated. If the pleural fluid is not thick pus, but the Gram’s stain is positive and white blood cell (WBC) counts are elevated, pleural drainage is recommended. Another indication for therapeutic thoracocentesis is the relief of respiratory distress secondary to a pleural effusion.

Many options exist for thoracic drainage, including intermittent chest drainage, use of an indwelling chest tube, pleural lavage, pleuroscopy and debridement, open chest drainage/debridement with or without rib resection in the standing horse, open chest drainage/debridement under general anesthesia, and lung resection under general anesthesia. Drainage of a pleural effusion can be accomplished by use of a cannula, indwelling chest tubes, or a thoracostomy. Thoracostomy is reserved for severe abscessation of the pleural space. Thoracocentesis is accomplished easily in the field and may not need to be repeated unless considerable pleural effusion reaccumulates.

Indwelling chest tubes are indicated when continued pleural fluid accumulation makes intermittent thoracocentesis impractical. If properly placed and managed, indwelling chest tubes provide a method for frequent fluid removal and do not exacerbate the underlying pleuropneumonia or increase the production of pleural effusion. The chest entry site and end of the drainage tube must be maintained aseptically. A one-way flutter valve may be attached to allow for continuous drainage without leakage of air into the thorax. If a chest tube is placed aseptically and managed correctly, it can be maintained for several weeks. It should be removed as soon as it is no longer functional. Heparinization of tubing after drainage helps maintain patency. Local cellulitis may occur at the site of entry into the chest but is considered a minor complication. Bilateral pleural fluid accumulation requires bilateral drainage in most horses.

Open drainage or thoracostomy may be considered when tube drainage is inadequate. Open drainage should not begin too early in the disease. An incision is made in the intercostal space exposing the pleural cavity and causing a pneumothorax. If the inflammatory process has fused the visceral and parietal pleura adjacent to the drainage site, a pneumothorax may not develop. The wound is kept open for several weeks while the pleural space is flushed and treated as an open draining abscess.

Pleural Lavage

Pleural lavage may be helpful to dilute fluid and remove fibrin, debris, and necrotic tissue. Lavage apparently is most effective in subacute stages of pleuropneumonia before loculae develop; however, pleural lavage may help break down fibrous adhesions and establish communication between loculae. Care must be exercised that infused fluid communicates with the drainage tube. Lavage involves infusing fluid through a dorsally positioned tube and draining it through a ventrally positioned tube (). In addition, 10 L of sterile, warm lactated Ringer’s solution is infused into each affected hemithorax by gravity flow. After infusion, the ventrally placed chest tube is opened and the lavage fluid is allowed to drain. Pleural lavage probably is contraindicated in horses with bronchopleural communications because it may result in spread of septic debris up the airways. Coughing and drainage of lavage fluid from the nares during infusion suggest the presence of a bronchopleural communication.

Differentiation From Neoplasia

Although pleuropneumonia is the most common cause of pleural effusion in the horse, the second most common cause is neoplasia. Differentiating between the two conditions is a challenge for the equine clinician because similarities exist in the clinical signs and physical examination findings.

Pleuropneumonia effusions are more likely to have abnormal nucleated cell count more than 10,000/μl (usually >20,000/μl) with reater than 70% neutrophils. Bacteria frequently are seen both intra- and extracellularly. A putrid odor may be present.

Neoplastic effusions have variable nucleated cell count. If caused by lymphosarcoma, abnormal lymphocytes may predominate. However, neoplastic cell often are not readily apparent and a definitive diagnosis may be difficult. Rarely do neoplastic effusions have a putrid odor. Bacteria are seen rarely in the cytology preparations.

Once again, use of ultrasonography helps determine if neoplasia is responsible for the effusion. Fibrin most commonly is detected in association with pleuropneumonia but has been detected in horses with thoracic neoplasia. Mediastinal masses associated with neoplasia may be readily visible (). Abnormal solitary masses on the lung surface may be visible in horses with metastatic neoplastic disease.

Comprehensive Management

The primary goals in managing a horse with pleuropneumonia are to stop the underlying bacterial infection, remove the excess inflammatory exudate from the pleural cavity, and provide supportive care. Ideally an etiologic agent is identified from either the tracheobronchial aspirate or pleural fluid and antimicrobial sensitivity determined. Without bacterial culture results, broad-spectrum antibiotics should be used because many horses have mixed infections of both gram-positive and gram-negative and aerobic and anaerobic organisms. Commonly used therapy is penicillin combined with an aminoglycoside such as gentamicin, enrefloxacin, trimethoprim and sulfamethoxazole, or chloramphenicol. Because of the need for long-term therapy, initial intravenous or intramuscular antimicrobials may need to be followed by oral antimicrobials. Preferably the oral antimicrobials are not administered until the horse’s condition is stable and improving because blood levels obtained by this route are not as high as those achieved by use of intramuscular or intravenous administration.

Treatment of anaerobic pleuropneumonia is usually empiric because antimicrobial susceptibility testing of anaerobes is difficult due to their fastidious nutritive and atmospheric requirements. Thus familiarity with antimicrobial susceptibility patterns is helpful in formulating the treatment regimen when an anaerobe is suspected. The majority of anaerobic isolates are sensitive to relatively low concentrations (22,000 IU/kg IV q6h) of aqueous penicillin. Bacteroides fragilis is the only frequently encountered anaerobe that is routinely resistant to penicillin, although other members of the Bacteroides family are known to produce B lactamases and are potentially penicillin-resistant.

Chloramphenicol (50 mg/kg PO q4h) is effective against most aerobes and anaerobes that cause equine pleuropneumonia. However, because of human health concerns the availability of chloramphenicol may decrease. Metronidazole has in vitro activity against a variety of obligate anaerobes including B. fragilis. Pharmacokinetic studies indicate a dose of 15 mg/kg intravenously or orally four times a day is necessary to maintain adequate serum levels. Oral administration rapidly results in adequate serum levels and thus is an acceptable route of administration for horses with pleuropneumonia. Metronidazole is not effective against aerobes and therefore always should be used in combination therapy at a dose of 15 mg/kg every 6 to 8 hours. Side effects of metronidazole include loss of appetite and lethargy; use of the drug should be halted when these signs are observed. Aminoglycosides and enrofloxacin should not be considered for the treatment of pleuropneumonia caused by an anaerobe unless these drugs are used in combination therapy with penicillin.

Ancillary Treatment

Antiinflammatory agents help reduce pain and may decrease the production of pleural fluid. This in turn may encourage the horse to eat and maintain body weight. Flunixin meglumine (500 mg ql2-24h) or phenylbutazone (1-2 g q12h) is commonly used for this purpose. In this author’s opinion, corticosteroids are contraindicated for the treatment of bacterial pleuropneumonia. Rest and the provision of an adequate diet are important components of the treatment of pleuropneumonia. Because the disease course and period of treatment are usually prolonged, attempts should be made to encourage eating. Intravenous fluids may be indicated in the acute stages of the disease to treat dehydration resulting from anorexia and third-space losses into the thorax.


Laser Surgery of the Upper Respiratory Tract

Lasers have become a common instrument for surgical and nonsurgical therapy in equine medicine. The many different tissue interactions that can be produced, the precision of its use, and the ability to apply laser energy to less accessible areas are the great advantages of the laser compared with other forms of therapy.

Laser is an acronym for Zight amplification of stimulated emission of radiation. The light emitted by lasers works according to the basic properties of light and electromagnetic radiation, but it is very different from the light produced by more common light sources such as incandescent bulbs, fluorescent lamps, or sunlight. The similarity between laser light and common white light is that all light consists of particles (photons) that travel through space in unique waveforms. White light consists of a mixture of many different wavelengths. Each color of visible light has its own characteristic wavelength. Visible light has an electromagnetic spectrum of wavelengths that range from approximately 400 nm to 700 nm.

Laser light can be within the visible spectrum of light, but it differs significantly from white light because of its monochromacity, collimation, and coherence. Laser light consists of a single wavelength or an extremely narrow range of wavelengths, and is therefore considered “monochromatic.” Also light emitted from bulbs or headlights diverge rapidly, but laser light has a very narrow cone of divergence. Finally, light waves can travel through space without any fixed relationship to each other, meaning they are incoherent. If all waves are lined up together so their peaks and valleys match, they are in phase, or coherent. Laser light is coherent, and white light is not.

The components to create laser light are an active medium, a power source, an optical resonator, and an output coupler (partially transmitting mirror). The active medium is the material that determines the wavelength of the laser. The medium can be a gas, a liquid, a solid material, or a junction between two plates of semiconductor materials. The power source is the pump that stimulates the emission of radiation and the type of energy used as a power source is determined by the lasing medium. The optical resonator can be thought of as mirrors on either side of the medium that reflects the light back into the medium for “amplification.” The output coupler allows a portion of the laser light contained between the two mirrors to leave the laser resonator in the form of a beam.

Lasers are characterized in two main ways. They can be delineated by the medium (diode, CO2, neodymium: yttrium-aluminum-garnet [Nd:YAG]) or the power output (pulsed vs continuous). A general classification system also exists for laser power and safety (classes I-IV). Classes I and II are low-risk lasers with a power of less than 1.0 mW. “Cold” or therapeutic lasers are class III lasers. All surgical lasers are class IV (>0.5 watts). Although the power is measured in watts, the power density is termed “irradiance” and is the amount of power per unit of surface area. Irradiance is equal to the laser power output/laser beam size (W/cm2). Therefore a larger beam size of a given power will have a smaller irradiance. The number of joules depicts the total energy, which is equal to the laser output (watts) multiplied by the exposure time (seconds). The “energy fluence” is equal to joules/laser beam size, and measures the total amount of energy directed to the tissue during a treatment. An understanding of this fact is important because the effectiveness of a particular laser is determined not only by its wavelength but also by how it is used.

Laser light interacts with tissue in several ways. It can be absorbed, transmitted, reflected, or scattered. The percentage of each interaction is dependent on the characteristics of the tissue and the laser light. The amount of absorption is dependent on the wavelength of the light relative to the chromophore content of the tissue (hemoglobin, keratin, protein, water, melanin). Each chromophore has its own absorption spectrum for different wavelengths of light. If the light is absorbed it is transformed into heat energy. Heating tissue to 60° C will lead to coagulation of proteins, and heating tissue to higher than 100° C will result in vaporization. Thus lasers will yield different biologic effects dependent on the energy absorption coefficient. Although vaporization and coagulation can be seen at the time of surgery, a zone of thermal injury exists beyond what can be seen at surgery. If a large amount of energy is expended that is not strictly focused on the area of interest, excessive swelling and trauma to the tissues may occur postoperatively.

Therapeutic Lasers

Lasers have become a common tool to speed healing in many different types of injuries. The lasers used for this purpose differ greatly from surgical lasers. Therapeutic lasers are considered “cold” or low-power lasers and fall into classes II and III. They may induce some heat but no greater than that which would be felt from a 60-W bulb held close to the skin. The benefits of these lasers are the analgesic effects caused by alterations in nerve conduction and wound healing caused by stimulation of changes in intracellular calcium that ultimately results in increased protein synthesis and collagen production. The most common lasers employed are the gallium arsenide (GaAs) and helium neon (HeNe) lasers at a distance of 1 to 2 mm from the surface of the target tissue for a total energy density of 5 J/cm2.

Surgical Lasers

Although surgical lasers have existed since 1960, it was not until lasers could be applied through small flexible fibers that these tools had an enormous impact on equine surgery. These fibers can be passed down the biopsy channel of a videoendoscope and employed under videoendoscopic control. This development revolutionized the treatment of upper respiratory conditions by providing the surgeon an opportunity to approach lesions within the nasal cavity, larynx, and pharynx without making a surgical skin incision. This new procedure also provided a technique for cutting a fairly reactive and very wellvascularized tissue that is precise and provides significant hemostasis.

The two most common lasers used for upper respiratory surgery are the diode and Nd:YAG lasers. They have wavelengths of 980 nm and 1064 nm, respectively, and can pass down a small flexible optical quartz fiber without significant disruption of wavelength. The diode laser has two main advantages compared with the Nd:YAG. The diode laser is a much smaller unit (less than 15 lb) and is significantly less expensive than the Nd:YAG. The major disadvantage of the diode laser is its power limitation of 25 W, whereas the Nd:YAG can exceed 50 W. Other lasers such as the CO2 cannot pass down a small fiber effectively because of their much larger wavelength and therefore cannot be used with a standard videoendoscope. Although the CO2 laser wavelength is strongly absorbed by water and therefore is an excellent precise cutter, it has only poor-to-fair coagulating capability. The diode or Nd:YAG wavelengths are diffusely absorbed by all protein molecules and therefore have greater coagulation capabilities, although they do not cut as well as the CO2 laser.

The laser can be used in contact or noncontact mode. Most surgeries can be performed with a bare fiber (no special tip) in contact mode. This method provides very accurate, controlled cutting and hemostasis of the small vessels in the respiratory mucosa, and provides the surgeon some tactile sense of the procedure. A lower power setting of 14 to 18 W is sufficient in most cases. This also means that a small very portable diode laser can be employed. If the laser is used correctly, little lateral thermal damage should occur. The surgeon resects the tissue by dragging the fiber across the tissue as he or she would lightly drag a scalpel blade. The types of surgeries commonly done in this fashion include axial division of epiglottic entrapment, resection of subepiglottic or pharyngeal cysts, vocal cord resections, resection of granulation tissue, and treatment of guttural pouch tympanites.

With noncontact laser surgery, the fiber is held 3 to 5 mm away from the target tissue. A higher power setting of 40 to 60 W is commonly required to work effectively, which requires an Nd:YAG laser. Noncontact surgery is used mostly for ablation of cystlike structures such as ethmoid hematomas or pharyngeal cysts and to vaporize membranous structures.

General Use

A great advantage of the use of lasers in respiratory surgery is that many of the surgeries can be done on the standing, sedated animal on an outpatient basis. This fact also equates to a shorter, easier postoperative management because no skin incision is present. Procedures can be performed with the animal standing in the stocks with just intravenous sedation such as xylazine (0.44 mg/kg). Repeated half doses or a longer-acting agent may be required depending on the procedure and the experience of the surgeon. With the horse sedated, a twitch is normally not required to pass the endoscope. The horse’s head can be suspended from cross ties for support, but an individual must always be positioned at the horse’s head for safety and to alter the head position as needed. Topical anesthetic is applied to the area of interest through polyethylene tubing that is advanced down the biopsy channel of the endoscope. The horse often swallows while the anesthetic is applied, and application should be intermittently suspended to make certain the anesthetic is applied appropriately in between swallows. The anesthetic is usually effective for approximately 2 hours, so the animal is not allowed to eat for 1 to 2 hours after surgery.

Laser safety should always be considered. Although the laser is used within the respiratory cavity, surgical personnel should still wear laser safety glasses as a precaution against any misfiring of the laser. The laser should always be kept in the standby mode when not being used. If a procedure is performed with the horse under general anesthesia near an endotracheal tube, the oxygen concentration should be decreased with helium to dramatically reduce the risk of spontaneous ignition. Smoke evacuation is usually not necessary in contact laser surgery in the standing horse but may be required in noncontact work or when the horse is under general anesthesia.

Antiinflammatory medication is the cornerstone of postoperative management in the upper respiratory tract. Phenylbutazone (4.4 mg/kg) and dexamethasone (0.044 mg/kg) are given in the immediate postoperative period. Both medications are recommended for several days at a decreased dose depending on the type of surgery and anticipated degree of inflammation. Local antiinflammatory medication can also be administered through a 10-Fr catheter that is advanced through the nasal passage into the nasopharynx. Ten milliliters of a mixture of dimethyl sulfoxide, glycerine, and dexamethasone solution are administered slowly through the catheter while watching the horse swallow. This mixture is administered twice daily for as long as 7 days.

Antimicrobials are not commonly given unless the surgeon is working on areas of thickened scar tissue where the vascularity may be compromised, or extensive use of the laser is required. Although vaporization of all tissue with the laser results in a sterile incision, the adjacent tissues of the throat and mouth can easily contaminate the open wound bed at the conclusion of surgery. Surgical inexperience can lead to greater thermal injury than visually appreciated and increased susceptibility to infection even in healthy tissues, particularly when the laser is used on subepiglottic tissues.

Laser Surgery of the Upper Respiratory Tract: Common Procedures


Although the laser has become an invaluable tool for many upper respiratory surgeries, its improper use can create significant trauma and irreparable damage. Great care should be taken to use only as much energy as necessary to complete the task and minimize extraneous firing. When used appropriately, the laser greatly diminishes the need for more extensive surgery and speeds the recovery of the patient.


Treatment of Arytenoid Chondrosis

Medical Treatment of Arytenoid Chondrosis

Acute inflammation associated with an arytenoid chondrosis can be treated aggressively with intravenous (IV) antimicrobials and antiinflammatory drugs, and may not require surgical intervention. Because it is difficult to get a bacterial culture to direct treatment, broad-spectrum antimicrobials are used. Potassium penicillin (22,000 IU/kg q6h), gentamicin (6.6 mg/kg q24h), phenylbutazone (4.4 mg/kg q12h), and dexamethasone (0.025-0.05 mg/kg q24h) are given intravenously. Because respiratory distress can be induced with any excitement, the horse should be kept in a quiet environment and monitored closely. An emergency tracheotomy kit should be kept stallside. Tracheotomy is reserved for situations in which the animal cannot be maintained in a quiet environment or when respiratory stridor is evident even when the animal is relaxed.

Within a few days dramatic improvement usually occurs with a decrease in the soft tissue swelling. Surgery is still not recommended at this point because many horses will continue to improve for 30 days with further rest and antimicrobial treatment. Horses are discharged with recommendations for oral antimicrobial treatment and 30 days of rest before endoscopic reevaluation to assess the need for further treatment. Horses that do not show dramatic improvement within the first few days on IV antimicrobial treatment, have gross purulent material draining from their arytenoid, or have swelling of the laryngeal saccule are taken to surgery more quickly. Swelling of the saccule indicates accumulation of purulent material abaxial to the arytenoid.

Further treatment is often predicated on the response to medical treatment and the proposed use of the horse. Several horses have gone back to racing after medical treatment alone despite having slightly abnormal looking corniculate processes of their arytenoids. These horses maintain good arytenoid abduction bilaterally. Those horses that have granulation tissue remaining on their arytenoid are best treated by laser excision of the tissue and rest. Several weeks are required for the mucosa to cover the defect before exercise can be resumed. If laryngeal function is still compromised sufficiently to compromise the horse’s athletic purpose, a partial arytenoidec-tomy should be considered. If the horse is intended to return to athletic performance, the clinician should ensure that one arytenoid has full function. If not it is unlikely an arytenoidectomy will be enough to return the horse to full athletic function.

Surgical Treatment of Arytenoid Chondrosis

A temporary tracheotomy must be performed so that the horse can be given anesthetic gas during the surgical procedure of partial arytenoidectomy. If too much laryngeal compromise exists initially, the tracheotomy should be performed with the horse standing to guarantee the horse a patent airway during induction of anesthesia. If a large enough lumen is present that an endotracheal tube can be passed through the larynx after anesthesia is induced, the tracheotomy is performed with the horse under general anesthesia and the endotracheal tube switched to the tracheotomy site once the horse has been anesthetized. This method will allow for a cleaner, smaller tracheotomy. Caution should be exercised so the tracheotomy site is not placed too far cranially. The position of the tracheotomy relative to that of the larynx is deceptive when the horse is under anesthesia and the head extended. If the tracheotomy is placed too far cranially it may become obstructed during recovery from anesthesia.

To perform an arytenoidectomy a standard laryngotomy approach is first made to the larynx. A headlamp is very useful for illumination while the clinician is working within the larynx. Placement of the endoscope through the nares in front of the larynx can also supplement light. Multiple techniques exist for performing partial arytenoidectomy. It is always best to try and salvage a mucosal flap on the axial side of the arytenoid to achieve primary mucosal closure after the arytenoid is removed to minimize the prospect of granulation tissue formation postoperatively. Before performing the arytenoidectomy, the clinician should remove the vocal chord and ventricle. This procedure leaves an opening at the ventral aspect of the arytenoidectomy site for any drainage of submucosal hemorrhage or clot abaxial to the final mucosal flap.

To form the mucosal flap, mucosal incisions are made from dorsal to ventral at the caudal border of the arytenoid and the rostral border, just caudal to the corniculate. These incisions are connected in a horizontal incision along the ventral border of the arytenoid. The mucosa is slowly dissected free from the arytenoid and left attached dorsally. The abaxial border of the arytenoid is then freed of its muscular attachments with primarily blunt dissection to minimize hemorrhage. The muscular process is isolated and transected. The clinician then elevates the arytenoid and frees it completely by cutting the remaining corniculate mucosa rostrally. Any remaining dorsal attachments are also cut and the cricoarytenoid joint capsule is cut caudally. Mucosa is held together to plan closure, and excess mucosa is trimmed. The caudal edge of the mucosal flap is apposed to the laryngeal mucosa in a simple continuous pattern with absorbable suture, with the clinician working dorsal to ventral. The rostral edge of the mucosal flap is apposed similarly to the remaining mucosa that was abaxial to the corniculate, in a parallel line to the caudal edge. The most difficult part of the incision is its very dorsal aspect; it is extremely important to close the dorsal aspect to prevent the formation of granulation tissue. The ventral aspect is left open to drain. Bleeding should be minimal once the mucosal edges are apposed. Any granulating “kissing” lesions on the opposite arytenoid should be debrided at this time. If extensive purulent material exists abaxial to the arytenoid, a mucosal closure is not performed. At the conclusion of surgery the endotracheal tube can be replaced with an equivalent size tracheotomy tube for the horse’s recovery from general anesthesia.

On the morning after surgery another endoscopic examination should be performed. A clear opening to the glottis should exist; if the clinician holds off the tracheotomy tube while watching the horse’s respiratory effort, laryngeal function can be assessed. If laryngeal function is adequate for the horse to breathe easily through its nares, the tracheotomy tube can be removed. The horse should be maintained on perioperative antimicrobials and antiinflammatories for 1 week while being maintained in a stall for 1 month. During this time, the horse can be allowed to graze under hand restraint. The tracheotomy and laryngotomy sites are left open to heal in by second intention. All feeding should take place from the ground to minimize the risk of aspiration. An endoscopic examination should be performed 1 month postoperatively to determine the presence of granulation tissue. Once mucosal healing is complete the horse should receive a 1-month turnout before resuming exercise.

Several potential complications of this surgery exist. The most common complications after an arytenoidectomy are granulation tissue or excessive residual mucosa. The clinician should remove this substance at the first month by videoendoscopic laser excision performed with the horse standing under sedation. If it is not removed in the early stages, the tissue may mineralize and make excision much more difficult later. A more serious, life-threatening complication is aspiration pneumonia. The risk of pneumonia may be dramatically decreased by less traumatic dissection of the arytenoid from the lateral musculature at the time of surgery. Many of these muscle bellies narrow the glottis while the horse swallows, thus playing a protective role. Another complication is postoperative noise. This postoperative respiratory noise most likely originates from vibration of the residual arytenoid/corniculate mucosa. An examination performed with the horse on a treadmill may be beneficial to make this determination. The adjacent aryepiglottic fold that is no longer held abaxially by the arytenoid can be the offending soft tissue that obstructs the airway. This tissue, or any residual arytenoid mucosa, can be identified during an endoscopic examination performed while the horse is exercising on a high-speed treadmill. The tissue should be removed as needed.


Axial Deviation of the Aryepiglottic Folds

Axial deviation of the aryepiglottic folds () has been recognized as a cause of dynamic upper respiratory obstruction in horses since the first use of high-speed treadmill exercise testing to evaluate poor performance. The membranous portions of the aryepiglottic folds, which extend from the abaxial margin of the epiglottis to the corniculate processes at the lateral aspect of the arytenoid cartilages, collapse axially to occlude the glottis during inspiration (). Horses with axial deviation of the aryepiglottic folds have poor performance and are often reported to “finish poorly” or “stop” near the end of a race. During inspiration at exercise, some affected horses make an abnormal noise that may sound similar to the “roar” associated with laryngeal hemiplegia. The cause is unknown, although immaturity may be a factor in younger horses and should be suspected if concurrent dynamic upper respiratory abnormalities are present.

Clinical Signs And Diagnosis

Affected horses are typically presented with a chief complaint from the owner of poor performance. Horses with axial deviation of the aryepiglottic folds may or may not make an abnormal upper respiratory noise during exercise. No breed or gender predisposition exists, and the condition has been diagnosed in Thoroughbreds, Standardbreds, and racing Arabians. The condition has been reported in racehorses from 2 to 8 years of age, but the percentage of 2- and 3-year-old horses that were diagnosed with axial deviation of the aryepiglottic folds in one hospital population was significantly greater than in the overall hospital population evaluated for poor performance.

Physical examination and endoscopic examination of the resting horse typically do not yield any abnormalities related to the condition. At endoscopic examination at rest, the membranous portion of the aryepiglottic folds of affected horses has no visible structural or functional abnormalities. Nasal occlusion during endoscopic examination, which mimics airway pressures generated during exercise, does not induce axial deviation of the aryepiglottic folds in horses that subsequently demonstrate the condition during treadmill exercise. Endoscopic examination during high-speed treadmill exercise is required to diagnose axial deviation of the aryepiglottic folds. axial deviation of the aryepiglottic folds most often occurs as a distinct clinical problem but also can occur with other upper airway abnormalities. Horses may be unilaterally or bilaterally affected. No association has been identified between the development of axial deviation of the aryepiglottic folds and subsequent dorsal displacement of the soft palate or other causes of dynamic upper respiratory abnormalities.

Severity of axial deviation of the aryepiglottic folds is evaluated based on the extent to which the membranous portion of the aryepiglottic folds collapse across adjacent structures of the larynx. With mild collapse, the fold remains abaxial to the vocal fold. Moderate cases have collapse of the fold beyond the vocal fold but less than halfway between the vocal fold and the midline. In severe collapse, the fold reaches or crosses the midline of the glottis. Mild collapse results in less than or equal to 20% obstruction of the glottis and may not be of clinical significance in some cases. Horses with moderate collapse have 21% to 40% obstruction of the glottis and those with severe collapse have been reported to have 41% to 63% obstruction.

Axial Deviation of the Aryepiglottic Folds: Treatment

Horses with moderate and severe cases of axial deviation of the aryepiglottic folds and those with clinically significant mild axial deviation of the aryepiglottic folds are candidates for surgical treatment. Transendoscopic laser excision of the aryepiglottic folds (TLEAF) to remove a 2-cm isosceles right triangle of tissue from each collapsing aryepiglottic folds with use of a neodymium/yttrium-aluminum-garnet or diode laser in contact fashion is recommended. This approach is easier to perform in a sedated, standing horse with topical anesthesia, but it may be performed successfully with the horse anesthetized in lateral recumbency. The procedure may also be performed with the horse under general anesthesia through a laryngotomy with conventional instruments. The disadvantage for the clinician of performing the procedure this way is the inability to see the exact tissue being resected relative to its normal position to the larynx. If surgical resection is performed through the laser with general anesthesia, the horse is nasotracheally intubated and heliox (70% helium, 30% oxygen) should be mixed with 100% oxygen to achieve a fraction of oxygen in inspired air equal to 0.4 to prevent ignition while the laser is activated.

For surgery with TLEAF in the standing animal, horses are sedated with xylazine hydrochloride (0.4 mg/kg IV). Additional doses of xylazine hydrochloride (0.2 mg/kg IV) may be required. A videoendoscope is inserted into the nasal passage ipsilateral to the target aryepiglottic fold and held in place by an assistant. Topical anesthesia is achieved with an aerosolized solution that contains benzocaine hydrochloride (14%), butyl aminobenzoate (2%), and tetracaine hydrochloride (2%; Cetacaine) administered through polyethylene tubing (PE-240; Becton Dickinson, Sparks, Md.) passed through the biopsy channel of the videoendoscope.

Bronchoesophagoscopic forceps (Richard Wolf Medical Instrument, Vernon Hills, 111.), 60 cm in length and bent manually to conform to the curve of the equine nasal passage and pharynx, are used to provide traction on the aryepiglottic folds during excision. These forceps are passed into the nasal passage contralateral to the target aryepiglottic fold and are manipulated by a second assistant. The free margin of the membranous portion of the aryepiglottic fold is grasped halfway between the arytenoid and epiglottic attachments and elevated caudodorsally (). The laser is set to 18 W of power and excision of the tissue is performed in contact fashion. Beginning rostrally and immediately adjacent to the epiglottic attachment, the clinician makes a horizontal incision in the mucosa by sweeping the fiber side to side and gradually cutting tissue in a rostral to caudal direction. The grasping forceps are then rotated to apply traction to the aryepiglottic fold in a rostromedial direction. A vertical incision is then made from dorsal to ventral to cut the tissue adjacent to its attachments on the corniculate process of the arytenoid cartilage. The vertical incision is extended ventrally to intersect the horizontal incision and the tissue is removed with the grasping forceps. For bilateral excision, the videoendoscope and forceps are positioned in reverse for excision of the contralateral aryepiglottic fold.

To excite the aryepiglottic fold with the horse under general anesthesia, the horse’s mouth is held open with a mouth speculum and the soft palate is manually displaced dorsally. Active suction is used to evacuate smoke from the pharynx. The videoendoscope, grasping forceps, and suction tubing are all positioned in the oral cavity to perform the same surgical procedure. Surgical excision has been performed through a laryngotomy; however, this approach does not afford the same visual perspective of the surgical field as does the videoendoscopic approach.

Broad-spectrum antimicrobial therapy is given preoperatively and continued for 7 days postoperatively because of the open mucosal wound created in the larynx by excision of the aryepiglottic fold. Antiinflammatory therapy is recommended and should consist of tapering courses of phenylbutazone (2 mg/kg orally twice daily for 3-4 days, then once daily for 3-4 days), prednisolone (0.8 mg/kg orally once daily for 7 days, then 0.8 mg orally every other day for 3 treatments then 0.4 mg/kg orally every other day for 3 treatments), in addition to a topical pharyngeal spray (37 ml nitrofurazone solution [0.2%], 12 ml dimethyl sulfoxide [DMSO; 90%], 50 ml glycerine, and 0.2 ml prednisolone acetate [5%]; 10 ml twice daily for 7 days). The pharyngeal spray is administered though a 10-Fr male dog urinary catheter (Monoject, division of Sherwood Medical, St Louis, Mo.) that is placed up the ventral meatus of the nasal passage to a point level with the medial canthus of the eye. The pharyngeal spray is given slowly. If the horse swallows during administration, the catheter is correctly placed in the pharynx.

Postoperative management instructions for horses that have TLEAF should include at least two weeks of daily hand-walking or turnout in a small paddock. Additional rest may be indicated if other surgical procedures are performed for concurrent airway problems. Follow-up endoscopy is recommended before returning the horse to training. Postoperatively, the edge of the tissue will look slightly more fibrous and concave but not dramatically different than the preoperative appearance.

Some horses, especially younger animals and those with multiple upper respiratory abnormalities, may benefit from conservative management with prolonged rest. Additionally, these horses may benefit from longer periods of time between races when returned to training.

Prognosis of Axial Deviation of the Aryepiglottic Folds

In a retrospective study of racehorses with an exclusive diagnosis of axial deviation of the aryepiglottic folds as the cause of their poor performance, 75% of horses that had surgical excision of the aryepiglottic folds and 50% of the horses managed with rest had improved performance. Improvement of the upper respiratory noise is more likely to occur with surgical treatment. No complications have been recognized after surgical excision, and no adverse effects on deglutition or laryngeal or pharyngeal function have been reported.


Treatment of Vasculitis

Treatment of purpura hemorrhagica and similar idiopathic vasculitides consists of the following: (1) removing the antigenic stimulus; (2) suppressing the immune response; (3) reducing vessel wall inflammation; and (4) providing supportive care. Any drugs given when the clinical signs occurred should be discontinued, or, if continued medication is necessary, an alternate drug should be chosen from a chemically unrelated class. A thorough examination should be performed to identify a primary disease process. Any bacterial pathogens should be cultured and an in vitro sensitivity performed. Because most cases of purpura hemorrhagica are a sequela of Streptococcus equi infection, penicillin (procaine penicillin G 22,000-44,000 U/kg IM q12h or sodium or potassium penicillin 22,000-44,000 U/kg IV q6h) should be administered for a minimum of 2 weeks unless specifically contraindicated. Any accessible abscess should be drained. If gram-negative bacteria are suspected or isolated, additional appropriate antimicrobial therapy should be used. Antimicrobial therapy is also indicated to limit or prevent secondary septic complications such as cellulitis, tenosynovitis, arthritis, pneumonia, and thrombophlebitis.

Systemic glucocorticoids are warranted because purpura hemorrhagica and other undefined vasculitides are most likely immune-mediated. In addition, systemic glucocorticoids reduce inflammation of the affected vessel walls and subsequent edema formation. Dexamethasone (0.05-0.2 mg/kg IM or IV q24h) or prednisolone (0.5-1.0 mg/kg IM or IV q24h) may be used; however, clinical experience indicates that dexamethasone is more effective during initial therapy. The minimum dose that provides a decrease in clinical signs should be used. After substantial reduction and stabilization of clinical signs, the dose of glucocorticoids may be decreased by 10% per day over 10 to 21 days. When the dose of dexamethasone is 0.01 to 0.04 mg/kg per day, it may be given orally; alternatively, prednisolone may be substituted at ten times the dexamethasone dose. The bioavailability of oral prednisolone is 50%; thus an effective parenteral dose administered orally may result in relapse of clinical signs. Prednisone is poorly absorbed from the gastrointestinal tract and is not detectable in the blood of most horses after oral administration; thus its use is not recommended. Hydrotherapy, application of pressure bandages, and hand-walking should be used to decrease or prevent edema. Furosemide (1 mg/kg IV q12h) may help reduce edema in severe cases. A tracheostomy may be indicated if respiratory stridor is present from edema of the nasal passages, pharynx, and/or larynx. Dysphagic horses should be supported with intravenous or nasogastric administration of fluids. Nutritional support may be necessary in horses with prolonged dysphagia. Nonsteroidal antiinflammatory drugs (flunixin meglumine 1.1 mg/kg IV, IM or PO q12h or phenylbutazone 2.2-4.4 mg/kg IV or PO q12h) are indicated to provide analgesia in horses with lameness, colic, myalgia, or other painful conditions. NSAIDs may also help reduce the inflammation in affected vessel walls.

Horses with equine viral arteritis do not require specific therapy because the majority of cases recover uneventfully. Glucocorticoids are contraindicated because vessel wall damage results from direct viral injury. Occasionally horses with severe clinical signs of lower respiratory disease will need antimicrobial therapy to prevent or treat secondary bacterial pneumonia. Horses with EIA are infected for life. Glucocorticoids are contraindicated because they may result in increased viral replication and occurrence of clinical disease. Horses with equine ehrlichiosis may benefit from glucocorticoid therapy; however, they should be treated with oxytetracycline to eliminate the organism (see: “Equine Monocytic Ehrlichiosis” and: “Hemolytic Anemia”). Horses with photoactivated vasculitis should be stabled during daylight hours to prevent any further exposure to sunlight. The vascular inflammation should be treated with systemic glucocorticoids in a regimen similar to that for purpura hemorrhagica. Topical applications of glucocorticoids with or without antibiotics are not effective. Irritating topical solutions should not be used.


Acquired Coagulation Disorders

Disseminated Intravascular Coagulation

Disseminated intravascular coagulation () is the most common hemostatic dysfunction in the horse. disseminated intravascular coagulation is an acquired process in which activation of coagulation causes widespread fibrin deposition in the microcirculation resulting in ischemic damage to tissues. Hemorrhagic diathesis occurs as a result of consumption of procoagulants or hyperactivity of fibrinolysis. In normal coagulation, thrombin activates the conversion of plasma soluble fibrinogen to the insoluble fibrin, which forms a clot. Simultaneously, the fibrinolytic system is activated to prevent tissue ischemia that would occur from persistent fibrin clots. The fibrinolytic protein that is primarily responsible for limiting fibrin clot formation and providing a mechanism for clot removal is plasmin. Antithrombin III and protein C also minimize clot formation by inhibiting the actions of thrombin and as well as some of the other clotting factors. In disseminated intravascular coagulation, antithrombin III and protein C become depleted as a result of overzealous activation of coagulation. This results in excessive, unchecked thrombin and clot formation, which in turn activates plasmin. FDPs are formed when plasmin degrades fibrin. As the FDPs begin to accumulate in the circulation, they contribute to the coagulopathy by inhibiting thrombin activity and by causing platelet dysfunction. The end result is the dynamic combination of disseminated thrombosis at the same time that clotting factor consumption and fibrinolysis potentiate bleeding.

Disseminated intravascular coagulation is not a primary disease; it occurs in conjunction with diseases that generate excessive procoagulant activity in the blood. Diseases related to the gastrointestinal system (e.g., strangulating obstruction, colitis, enteritis), sepsis, renal disease, hemolytic anemia, and neoplasia are the most common primary diseases associated with disseminated intravascular coagulation. In one study, 96% of the horses that developed disseminated intravascular coagulation over a 5-year period were diagnosed with colic that required surgical intervention. Horses with devitalized intestine that required resection and anastomosis were more likely to develop disseminated intravascular coagulation than those horses in which resection and anastomosis was not required. Because endotoxin is a prominent feature of ischemic or inflammatory disease of the equine gastrointestinal tract, it is a logical conclusion that endotoxemia is the underlying pathophysiologic event that most commonly triggers disseminated intravascular coagulation. Endotoxin can initiate disseminated intravascular coagulation by several mechanisms: (1) direct damage to the endothelium, thereby releasing tissue factor; (2) induction of tissue factor expression and cytokine synthesis by mononuclear phagocytes; (3) direct activation of factor XII; (4) stimulation of thromboxane A2 synthesis by platelets which promotes irreversible platelet aggregation; and (5) inhibition of fibrinolysis by increasing production of plasminogen activator inhibitor.

Clinical Signs

Clinical signs of disseminated intravascular coagulation range from mild thrombosis and ischemic organ failure to petechiae and hemorrhage. In contrast to humans, frank hemorrhage associated with disseminated intravascular coagulation is rare. Petechial or ecchymotic hemorrhages of the mucous membranes or sclerae, epistaxis, hyphema, and melena can occur. Hypoperfusion and microvascular thrombosis lead to focal or widespread tissue damage and culminates in colic; laminitis; and signs of renal, pulmonary, and cerebral disease. Peripheral veins are susceptible to spontaneous thrombosis as well as increased thrombus formation after catheterization or simple venipuncture. Clinical signs of the primary underlying disease may overshadow the initial signs of disseminated intravascular coagulation.


A single test cannot confirm disseminated intravascular coagulation. The presence of clinical signs — thrombocytopenia, prolonged APTT and PT, and an increase in FDP concentration (>40 fig/ml) — is consistent with disseminated intravascular coagulation. In the early stages of disseminated intravascular coagulation, FDPs may not be increased. Monitoring changes over time can help decipher difficult cases, as thrombocytopenia and prolongation of the PT are frequently the only abnormalities initially detected. Hypofibrinogenemia is an uncommon finding in the horse; in fact, fibrinogen concentration may be increased, depending on the duration of the underlying primary disease. Reduced antithrombin III activity (<80% normal) also supports a diagnosis of disseminated intravascular coagulation.

Treatment and Prognosis

Determining the correct therapy for disseminated intravascular coagulation is difficult and controversial. Identification and treatment of the underlying disease process is paramount. Intravenous fluid therapy is necessary to maintain tissue perfusion and combat shock. If a septic process is present, antimicrobials are indicated. If a strangulating intestinal obstruction is present, immediate surgical correction is warranted. Minimizing the effects of endotoxemia may attenuate the disease process (see Chapter 3.7: “Endotoxemia”). Flunixin meglumine (0.25 mg/kg IV q8h) will mitigate the detrimental effects of eicosanoids. Corticosteroids are contraindicated because they potentiate the vasoconstrictive effect of catecholamines and reduce the activity of the mononuclear phagocyte system, which exacerbates coagulopathy by enabling FDPs to accumulate.

Fresh plasma therapy (15-30 ml/kg of body weight) is indicated with severe hemorrhage. It should be noted that administration of plasma could exacerbate thrombosis by supplying more clotting factors to “fuel the fire.” Fresh whole blood can be given if anemia is present from blood loss. Although its use remains controversial, administration of heparin (20 to 100 U/kg SQ q8-12h) in conjunction with fresh plasma may minimize clot formation by potentiating the anticoagulative effects of antithrombin III. Thus if heparin therapy is to be used, adequate antithrombin III must be present. Heparin can cause thrombocytopenia, hemorrhage, and reversible erythrocyte agglutination. If heparin is used, the packed cell volume should be closely monitored for a sudden decline. Low-molecular-weight heparin (Fragmin, Kabi Pharmacia AB; Stockholm, Sweden; 50 U/kg SQ ql2h) does not cause agglutination of equine erythrocytes, but its use may be cost-prohibitive. The prognosis for disseminated intravascular coagulation depends on the severity of the underlying disease and the response to therapy. In general, the prognosis is guarded to poor. In humans, the mortality rate is 96% when the antithrombin III activity falls below 60%.

Warfarin and Sweet Clover Toxicosis

Horses may develop hemorrhagic diathesis after consuming warfarin for therapeutic reasons, rodenticides, or moldy sweet clover (Melilotus spp.). Warfarin has been used for treatment of thrombophlebitis and navicular disease. Combination of warfarin with other protein-bound drugs, such as phenylbutazone, results in toxic accumulation in the plasma. Sweet clover hay or silage that is improperly cured can contain dicumarol. The toxin is not present in the living plant. The pathogeneses of warfarin and sweet clover toxicosis are identical. Dicumarol and warfarin competitively inhibit vitamin K, which is necessary for the production of clotting factors II, VII, IX, X.

The clinical signs of warfarin or dicumarol toxicosis include hematomas, hematuria, epistaxis, and ecchymoses of the mucous membranes. Absence of petechial hemorrhages can distinguish warfarin and dicumarol toxicity from disseminated intravascular coagulation. The diagnosis is made based on history of exposure and laboratory data. Clinical pathology reflects prolonged PT first because the plasma half-life of factor VII is shorter than the other clotting factors. The APTT becomes prolonged, but the platelet count remains normal.

Treatment for warfarin toxicity may only require discontinuation of the drug. If accidental exposure to rodenticides or dicumarol occurs, treatment with vitamin K, (0.5 to 1 mg/kg of body weight SQ q6h) 3 to 5 days is recommended. Therapy should be guided by measuring PT. Vitamin K3 causes acute renal failure and should not be given to horses. In an acute crisis, plasma or a whole blood transfusion may be indicated.


Immune-Mediated Hemolytic Anemia

Immune-mediated hemolytic anemia () results from cross-reacting antibodies that induce enhanced red blood cell removal. Autoimmune (primary immune-mediated hemolytic anemia) hemolysis results from loss of self-tolerance and is relatively rare in horses. Most commonly, hemolysis results from adherence of cross-reacting antibodies to erythrocyte surface antigens (secondary immune-mediated hemolytic anemia). The presence of these molecules on red blood cells causes intravascular destruction by complement activation (IgM-mediated) or — most commonly — extravascular removal by macrophages. It is important for the reader to consider that any infectious agent — especially equine infectious anemia, Babesia organisms, and Anaplasma phagocytophila; exogenous substances such as penicillin and phenylbutazone; or neoplasia — may cause alterations in epitopes of the erythrocyte membrane or neoantigens that contribute to enhanced removal by immune mechanisms. Therefore identification of the inciting cause is important for complete resolution of the hemolytic crisis.

Several possibilities may explain the onset of cellular destruction. The basic mechanisms involve a change in the red blood cell or an alteration in immunologic control of self-recognition. For example, a change in the red blood cell membrane may form a novel antigen that evokes an immune response. Drugs, neoplasia, or infection may induce changes in red cell antigens. Infectious agents that express similar antigens as host red blood cell antigens result in pathogen-induced immune-mediated hemolysis, termed molecular mimicry. An example of molecular mimicry is human infection with Epstein-Barr virus. Genetic predispositions may cause a failure of self-tolerance. Failure of autoregulation has been suggested to result from reduced suppressor lymphocyte control. Finally, failure of appropriate erythropoiesis may result from precursor erythrocytes being targeted by the immune response in a manner similar to that of circulating red blood cells. The goal of the clinician should be to focus on identifying any potential inciting causes because this will allow for appropriate case management with the best prognosis for efficient and complete disease resolution.

Immune-Mediated Hemolytic Anemia: Clinical Signs and Diagnosis

Horses with immune-mediated hemolytic anemia most commonly present with signs of extravascular hemolysis, but intravascular hemolysis is possible, especially when IgM antibodies or complement is involved. Spherocytes may be present on cytology of peripheral blood smears. Diagnosis based on autoagglutination will suggest surface-bound antibody. Dilution of the sample with saline (1:1) will indicate whether true agglutination is present. If erythrocytes still agglutinate after dilution, they can be considered positive for surface-bound antibody molecules. Tests that are used for the diagnosis when autoagglutination is absent are the direct and indirect Coombs’ test; the direct test is more sensitive. The Coombs’ reagent is polyclonal sera directed against equine IgG, IgM, IgA, and C3 and is used in serial dilutions. The endpoint of the Coombs’ test is agglutination, but it can also be used to test for antibody- or complement-mediated lysis. Direct Coombs’ test may yield a false-negative result if an incomplete set of reagents is used, if blood is not tested at both 4° C and 37° C, or if severe hemolysis has resulted in removal of the majority of antibody-coated RBCs from circulation. As previously described, a new direct immunofluorescence assay that uses class-specific antibodies to equine IgM, IgG, and IgA and flow cytometry has an increased sensitivity to detect red cell antibodies for the diagnosis of immune-mediated hemolytic anemia.

Treatment of Immune-Mediated Hemolytic Anemia

Therapy will be determined based on the level of anemia. In severe cases, whole blood transfusion may be indicated. Specific guidelines are given under Blood and Blood Component Therapy (see: “Blood and Blood Component Therapy”). Current drug administration should be discontinued. If, based on confirmed sepsis, antimicrobial therapy is required, drug therapy should be continued with a molecularly dissimilar drug. After blood samples for diagnostic tests (i.e., Coombs’ test or direct immunofluorescence assay) are obtained, immunosuppressive therapy may be considered. Most affected horses require immunosuppression with corticosteroids. Because immunosuppression carries the risk of potentiating infectious agents, underlying infectious disease conditions such as equine infectious anemia should be ruled out. Glucocorticoid therapy benefits the patient in the short term by reducing the function of macrophages to recognize antibodies complexed to red blood cells and in the long term by altering antibody production by B-lymphocytes. Dexamethasone used at 0.05 to 0.2 mg/kg IV q24h has been reported to have the greatest efficacy in treating immune-mediated hemolytic anemia in horses. The packed cell volume should be monitored carefully during the course of steroid therapy, and if the patient does not respond quickly, the frequency of administration may be increased to twice daily. In some instances, it may take up to a week for the full effect of steroid therapy to be reflected by a rise in packed cell volume. Once the packed cell volume is stable at greater than 20%, the steroid therapy should be carefully tapered by 0.01 mg/kg/day, while the horse is closely monitored for recurrence of hemolytic crisis. The major adverse reactions to long-term administration of corticosteroid in horses are laminitis, tendon laxity or weakness, and immunosuppression that leads to secondary infections. Therefore the goal is to reduce to the lowest effective dose as soon as possible. Alternate day therapy should be administered for the last week of therapy. Some individuals may require therapy for several weeks until disease resolution occurs. Although only a single equine case report has been published, the use of azathioprine (5 mg/kg PO q24h) and cyclophosphamide (300 mg/m2 body surface area) was successful in managing a case of refractory immune-mediated hemolytic anemia.


Anemia Due To Bone Marrow Aplasia Or Myelopthisis

Aplastic anemia results from congenital or acquired developmental failure of hematopoietic progenitor cells in the bone marrow. In other species, acquired aplastic anemia has been associated with bacterial and viral infections, chronic renal or hepatic failure, irradiation therapy, and drug administration, but the majority of cases are considered idiopathic. Until recently, aplastic anemia had only been reported in a few horses. No definitive cause was identified, although one horse had a positive Coombs test, thus suggesting an immune-mediated process. Phenylbutazone was implicated in two other cases. In the 1990s the advent of unapproved administration of a human recombinant erythropoietin to racehorses resulted in the emergence of a drug-induced immune-mediated anemia characterized by potentially fatal bone marrow erythroid suppression.

Endogenous erythropoietin, produced by the liver and activated in the kidney, stimulates red blood cell production by the bone marrow, thereby regulating maintenance of a normal peripheral red blood cell count. In an attempt to enhance performance by increasing circulating red cell mass, recombinant human erythropoietin (Epogen) has been administered to healthy racehorses. The recombinant product induces the production of antierythropoietin antibodies that cross-react with the horse’s endogenous erythropoietin. Endogenous erythropoietin thus is inactivated, and bone marrow red cell production is depressed. Complete shutdown of red cell production that results in fatal aplastic anemia has been reported in horses that were administered repeated doses of human recombinant erythropoietin. Local racing commissions should be contacted concerning any suspected case.

Clinical Signs, Diagnosis, and Treatment

Horses with advanced anemia caused by bone marrow hypoplasia show nonspecific clinical signs such as poor performance and weight loss as well as pale mucous membranes. Definitive diagnosis of aplastic anemia is based on bone marrow assessment. In two horses with erythroid hypoplasia and anemia after administration of recombinant human erythropoietin, bone marrow myeloid/erythroid ratios were 6.7 and 3.2 (normal 0.5-1.5), thus indicating severe, nonregenerative anemia. These horses also had increased serum iron concentrations, normal total iron binding capacities, and increased serum ferritin concentrations. Recombinant human erythropoietin can be detected in the plasma of horses for only 72 hours after dosing. Use of recombinant human erythropoietin can be suspected in horses if anti-EPO antibodies are detected in the patient’s serum or if endogenous erythropoietin levels are abnormally low (EPO Trac RIA, Incstar, Stillwater, Minn.).

In addition to aplastic anemia, pancellular bone marrow destruction secondary to neoplastic infiltration or myelofibrosis has been reported in the horse. In such cases, clinical signs are associated with loss of the shorter-lived cells, neutrophils, and platelets. Therefore fever, localized infection, and thrombocytopenic hemorrhage can be anticipated.

Treatment of aplastic anemia is focused on identification of underlying cause and on corticosteroid administration. Steroids stimulate erythropoiesis by increasing erythropoietin production and the sensitivity of stem cells to this hormone’s action. One horse with idiopathic aplastic anemia improved after administration of nandrolone decanoate (Deca-Durabolin), an anabolic steroid, and corticosteroids, and two horses with human recombinant erythropoietin-induced anemia recovered after drug withdrawal and administration of corticosteroids.

No successful treatment currently is available for myelophthisic diseases associated with pancytopenia.


Perineal Lacerations

Perineal lacerations occur during unassisted foaling, most commonly in primiparous mares. Lacerations are caused by a combination of foal limb malpositioning and the violent, unpredictable expulsive efforts that accompany equine parturition. The foal’s hooves can engage the roof of the vestibule during forceful contractions and may lacerate the dorsal wall of the vestibule. The resulting injury is classified as either a first, second, or third-degree perineal laceration, or a rectovestibular fistula. First-degree lacerations involve only the vestibular mucosa and vulvar skin at the dorsal commissure. Second-degree lacerations involve the vulvar mucosa, submucosa, and perineal body musculature. Third-degree lacerations result from the foal’s foot perforating the rectum and tearing all the structures between the rectum and vestibule caudally to include the dorsal vestibular wall, rectum, perineal body, and anal sphincter. Third-degree lacerations result in a common opening between the rectum and vestibule. Rectovestibular fistulas result from the foal’s foot perforating the rectum but then withdrawing the foot before subsequent normal delivery. The result is a fistula of variable size between the rectum and vestibule, usually cranial to the perineal body. The external genitalia in these cases will appear normal.

Diagnosis of these conditions is made during the post-partum examination, although third-degree perineal lacerations will be immediately obvious to the owner and may cause serious alarm (). Injury to the perineal body, anal sphincter, and dorsal vulvar commissure are readily apparent on visual inspection. Even with less severe injuries, external examination of the perineum will usually reveal edema, bruising, stretching, and splitting of the vulvar skin and mucosa. Speculum and manual examination are necessary to determine the degree of injury to the vestibule and vagina. Rectal palpation will confirm the presence of a rectovestibular fistula. Although other peri-parturient injuries may simultaneously occur, no reported associations exist with the occurrence of perineal lacerations. Thus no reason exists to be unduly concerned about the potential for other foaling-related injuries that may not be detected on a routine postpartum examination.

Classification of the type of laceration on the basis of the involved structures is useful because it will accurately predict the required treatment. First-degree lacerations will heal uneventfully with no surgical intervention other than possibly a Caslick’s procedure. Second-degree lacerations frequently will heal completely without intervention because the tissues are maintained in apposition. Damage to the perineal body or vestibular musculature that does not completely heal can be repaired at a later date. Third-degree lacerations and rectovestibular fistulas will always require surgical repair. However, immediate surgery is ill advised regardless of the type of injury. In the acute phase the wounds are extremely edematous, contaminated with feces, and some tissues may not be viable. Repair must be delayed at least 4 to 6 weeks until complete healing has occurred before reconstruction of the damaged perineum is attempted. During this interval, any devitalized tissue will slough and second intention healing will occur. Fibroplasia will take place and remodeling of the deposited fibrous tissue provides greater holding power for sutures. Complete epithelial resurfacing occurs so that visual examination of the laceration will reveal a line of junction where the rectal mucosa meets the vestibular mucosa (). Reconstructive surgery may be performed at any time after complete healing has occurred. Surgery performed 6 to 8 weeks postfoaling is optimal; however, other management concerns such as weaning of the foal or getting the mare in foal for next year often factor into the timing of the surgical repair. It is advisable to forewarn owners contemplating surgical repair that more than one attempt is often required to achieve reconstruction.

Treatment of Perineal Lacerations

Immediate treatment should be directed at medical management to minimize discomfort, prevent infection, and promote wound healing. Tetanus prophylaxis is indicated according to the recommended guidelines. Pain and inflammation secondary to trauma should be treated with phenylbutazone (4.4 mg/kg PO q24h). The wounds are invariably severely contaminated and thus benefit from broad-spectrum antimicrobial treatment. Antimicrobial therapy may be discontinued in 7 to 10 days once a healthy bed of granulation tissue is present. Affected mares may experience difficulty in defection as a result of perineal discomfort, and impaction can be a secondary complication. The feces can be kept soft by initial prophylactic administration of mineral oil through a nasogastric tube, and then with subsequent doses administered in the feed. Mares on lush green pasture may not require assistance to achieve fecal softening. Local wound care involves providing as clean an environment as possible. Manual evacuation of feces from the vestibule is beneficial in the early stages of healing for third-degree lacerations and rectovestibular fistulas. Gross fecal contamination of the vagina and uterus is seldom a concern because the injuries invariably occur caudal to the vestibular sphincter. Daily, or twice daily, lavage of the wound with antibacterial solutions such as dilute povidone iodine (10 ml of 10% stock solution/L of water) is beneficial for the first few days. The practitioner should resist the urge to aggressively surgically debride the lacerated tissues. Surgical repair depends on reconstruction of the shelf between the rectum and the vestibule. Retention of as much viable tissue as possible will improve the chances for successful surgical reconstruction. Tissue that is clearly non-viable should be promptly removed; however, the trauma and associated inflammation may make it difficult to differentiate between viable and nonviable tissues. This difficulty can easily result in removal of viable tissues. It is preferable to take a more conservative approach and to de-bride the laceration over several days, each time removing only the definitively nonviable tissue.

Mares with first- or second-degree lacerations seldom require surgery. Third-degree lacerations and fistulas result in chronic, low-grade bacterial contamination of the vagina and uterus; therefore surgical repair will be required for breeding soundness. Uterine contamination and subsequent endometrial degeneration secondary to these injuries has been documented by culture and biopsy. Any inflammatory uterine changes are reversible after surgical repair. Studies have shown that 75% of mares are able to successfully carry a foal after surgical repair of third-degree perineal lacerations or rectovestibular fistulas. Mares that have undergone surgical repair are predisposed to reinjury on subsequent foalings; however, clinical experience indicates that the incidence of recurrence is low.