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by Elizabeth Rozanski, DVM
Blaze, a classy black feminine Greyhound with big eyes and even bigger heart, had been limping intermittently for several months. Several trips to the veterinarian, multiple x-rays, and a variety of therapies had failed to relieve her discomfort. Finally, one day she appeared to be feeling poorly and came to the Foster Hospital for Small Animals at Tufts University in Grafton, Massachusetts. Upon examination, the pulses within Blaze’s femoral arteries were decreased to absent. Ultrasound was performed and a large blood clot (thrombus) was found within the aorta and extending down into the femoral arteries. The blood clot was preventing adequate blood flow and oxygen from reaching her back legs and causing her pain and discomfort. Blaze was treated with a clot-buster drug named streptokinase, with blood thinners, and with specialized cardiovascular surgery to remove the blood clot with a special type of catheter. However, ultimately, the treatment was not enough and Blaze lost her fight.
Aortic thromboembolism (ATE), or saddle thrombus as it is more commonly called, is a disease of apparently increasing frequency in the retired racing Greyhound population. The aorta is the largest artery in the body and carries blood away from the heart for distribution to the rest of the body. Blood flows through the aorta rapidly (typically at a speed of three feet/second). At the end of the aorta, by the pelvis, the aorta divides into three blood vessels. Blood clots tend to get lodged at this point and this will decrease or eliminate blood flow to the legs. Blood clots may either form at this location (called a thrombus) or may travel to this location after initially forming at another site (called an embolus). It is often hard in dogs to know where the clot formed, so the term “thromboembolus” is used to reflect the uncertainty of its origin.
Mechanism of development
Blood within the circulatory system normally does not clot until exposed to air or until the vessel is damaged. Blood clots are thought to form in circulation due to problems in one of three areas. These are that 1) the blood has an exaggerated tendency to clot (a hypercoagulable state) so that clots form in the blood stream; 2) stasis (or stagnant flow) of the blood; or 3) damage to the blood vessel or lining of the blood vessel. The clotting system in dogs is made up of platelets and clotting factors (proteins) which promote the development of clots. The blood also contains anticoagulant proteins which prevent the blood from clotting prematurely. In the normal animal, there is a tightly controlled balance of clotting factors and anticoagulant proteins which prevent both life-threatening hemorrhage and the formation of intravascular clots. Blood clots appear most likely to form if there are diminished anticoagulant proteins. In dogs, a specific anti-thrombotic named antithrombin III, has been most widely associated with the development of blood clots within blood vessels. Often, no matter the underlying cause, treatment of blood clots is directed at decreasing the ability of the blood to clot with various medications (commonly referred to as blood thinners).
Blood that is not flowing freely or has pooled in certain location too long (stasis) is also more likely to develop clots. This is a problem that has been recognized in animals with dilated, poorly functioning hearts. In this case, the blood swirls around in the heart for some length of time until eventually getting ejected into the aorta. During the time that the blood is not moving forwards, it is more likely to clot. This clot can then break loose from the heart and lodge in the aorta. Due to the mechanics of blood flow, clots typically go toward the pelvis, although rarely they can affect a front limb or even the brain. Blood stasis may also be responsible for the development of blood clots in animals that are paralyzed, recumbent, or that have intravenous catheters in blood vessels.
Damage to the lining of the blood vessel or the vessel itself may be responsible for clot formation. In recent years, medical knowledge concerning blood vessels had grown exponentially. The blood vessel was originally considered just a transport system for the blood, but now it is understood that the blood vessels contain cells that line the walls (endothelial cells) that actively work to prevent thrombus formation.
Additionally, in normal animals, any clots that are formed are rapidly broken down by a clot-dissolving system called the thrombolytic system. This is a tightly balanced enzyme-based system that act to literally dissolve the clots and to restore normal blood flow. It is thought that some animals may have deficiencies in their body’s ability to break down clots.
Aortic thromboembolism is typically identified clinically by the “5 Ps:” pain, pallor, pulselessness, paresis, and pollikothermy (cold). Aortic thromboembolism is a condition that has been widely recognized in cats with heart disease for years. Affected cats develop a sudden onset of hind limb paralysis that is frequently accompanied by severe pain and occasionally by heart failure (difficulty breathing due to fluid in the lungs). Advanced diagnostic imaging such as ultrasonography or angiography can confirm the diagnosis if it unclear based upon examination. Cats with heart disease often develop an enlarged chamber of their heart (left atrium) that seems predisposed to formation of clots, likely due to both blood stasis and endothelial damage. Additionally, cats may have over-active platelets which may promote blood clotting.
In dogs, however, aortic thromboembolism is a relatively rare condition. In direct contrast to cats, clinical signs are usually insidious in onset. Additionally, dogs with ATE are often able to walk but are weak and may have one hind leg that seems more affected than the other. Dogs appear to have a better developed collateral circulation; this means that their legs are often supplied with blood from other sources such as branching arteries before the site of the clot. Aortic clots may also not completely block the entire aorta, but rather let some blood pass by the obstruction.
Clinical signs in dogs usually reflect hind limb weakness. In dogs, this is frequently considered arthritis, particularly in older previously active dogs. Owners often note difficulty in rising, jumping, and exercising. Signs may wax and wane over a period of several days to even several months. In some dogs, clinical signs develop acutely, like in cats. Occasionally, owners detect wounds near the toes that have developed from absent circulation to the skin (infarction and necrosis). Most often, dogs have been otherwise assessed as feeling well. In some cases, partial inappetance is present, or rarely, vomiting, diarrhea or rapid breathing.
Physical examination findings
In a Greyhound affected by an aortic thromboembolism, physical examination usually reveals markedly decreased to absent pulses in the hind legs. Femoral pulse can be easily felt in dogs at the middle of the their inner thigh, where the body and the leg joins. Often, the blood clot itself can be felt as a corded structure in the region of the artery. Other physical examination abnormalities will reflect concurrent diseases or response to pain. An index of suspicion is often required by the attending veterinarian in order to detect abnormalities in pulse quality, as pulses may be difficult to feel or disregarded in an animal presented for lameness evaluation.
If an aortic thromboembolism is suspected, further diagnostic testing is warranted. Testing usually focuses on 1) confirming the clot and 2) looking for an underlying reason. Tests to confirm the clot’s presence include abdominal ultrasound with Doppler examination of the aorta or angiography. With ultrasound examination, the clot may be seen as a hyperechocic or brighter white structure within the middle of the aorta and blood flow through the aorta is decreased or absent. Angiography is a more invasive but potentially more accurate test to confirm the clot’s presence. With angiography, a special catheter is placed in the aorta and a sterile dye is injected to highlight the points of decreased or absent blood flow. Angiography requires sedation or general anesthesia and specialized equipment (cardiac catheters, fluoroscopy) and training.
Blood testing is also recommended to determine if there are any abnormalities that may affect the dog’s overall health or be responsible for the clot. This testing typically involves a complete blood count (CBC) to look for anemia, leukemia, or platelet abnormalities; a serum chemistry profile to evaluate kidney and liver function, to check protein levels, and electrolytes; a urinalysis to evaluate for kidney disease and protein loss; and a thyroid level, as hypothyroidism may trigger clot formation. Further additional testing that is frequently performed includes a complete abdominal ultrasound to evaluate for signs of cancer, an echocardiogram to evaluate the heart’s function, and chest radiographs to look for infection or cancer. Specialized clotting tests are also frequently performed to look for signs of abnormalities in the clotting system. Antithrombin III, a strong anti-thrombotic, may also be directly measured in the blood stream.
Treatment options vary depending on if an underlying abnormality has been identified. If a specific problem has been found, therapy (such as thyroid supplementation or chemotherapy) should be directed at treatments for that specific disease. Additionally, with or without identification of an underlying cause, therapy should be directed at treating the clot that is present and preventing the development of new clots. Options directed at treating the underlying clot include treatment with a clot-dissolving drug or surgical removal of the clot. Streptokinase is the drug that has been most widely used in clot dissolution therapy in dogs. It is a drug that acts to speed up the normal thrombolytic (clot-dissolving) process in the body. It is given either as an intravenous infusion or directly onto the clot with a special catheter. The drug, which is designed for use in people, is expensive, costing about $500 for a dose. Streptokinase is particularly helpful in newly formed clots, although in most dogs a reduction in clot size is detected upon ultrasound examination. In cats, streptokinase therapy has been associated with a devastating syndrome called reperfusion injury. This means that when blood flow (perfusion) is re-established to the back legs, poisons (potassium, lactate, acids) that have formed in the muscle tissue due to the lack of oxygen are released into the general circulation, potentially resulting in shock and death. Reperfusion injury is not frequently observed in dogs, likely due to the presence of collateral circulation but remains a risk with any form of therapy that suddenly changes blood flow to any region in the body.
Blood clots may be surgically removed by threading a specialized cardiac catheter up the artery and pulling out clots, or by an abdominal surgery that permits an incision (arteriotomy) directly over the blood clot. Catheter-directed clot removal is less invasive and is successful in some dogs. Direct surgical removal is accompanied by a large anesthetic and bleeding risk, but may also be effective. The choice of which method to directly address the clot is usually based upon preferences of the attending veterinary clinician and dog’s family members. In some cases, no direct therapy for the clot in chosen and instead therapy is directed at preventing the formation of new clots and hopefully allowing the body’s own thrombolytic system to remove the remaining clot.
Therapy with medications to prevent the formation of new clots is indicated in all dogs with aortic thromboembolism. There are several options available to try to prevent new clots. In general, there is no perfect therapy. The three major medications used to try to control hemorrhage are aspirin, heparin and warfarin.
Aspirin, just like in people with heart disease, will inhibit platelet function at low doses. This can decrease the likelihood for the formation of platelet-rich thrombi. The low dose, typically 40 mg (one-half baby aspirin) for a Greyhound rarely will cause side effects and is very economical. At higher dose, aspirin is occasionally responsible for intestinal irritation (vomiting, ulcer formation). Aspirin therapy, while beneficial, does not appear to have high enough potency to be used as a sole agent for the treatment of arterial thromboembolism. It is often used in conjunction with other therapy.
Heparin is another drug that may be used to try to prevent the development of blood clots. Heparin acts by dramatically enhancing the ability of antithrombin III to act as an anticoagulant. Antithrombin III is able to inhibit the activity of factors II, IX, X, XI and XII. Heparin is a very strong anticoagulant and is very effective at preventing the formation of new clots. However, it must be given 3-4 times a day by injection and over time, as the body’s antithrombin III levels are consumed by accelerated use, heparin’s efficacy falls and the dose must be increased to maintain its blood thinning actions. Side effects of heparin therapy include increased risk of bleeding. Regular heparin cost to treat a Greyhound would be approximately $1/ day and a patient would require coagulation evaluation (called an activated partial thromboplastin time-aPTT) about once every two to three weeks. Recently, in human medicine, a specially processed type of heparin, called low-molecular weight heparin (LMWH) has become available for long-term anticoagulant therapy in people. Some veterinarians have used LMWH in dogs because it is easy to give (one to two times a day) and does not require any monitoring of blood coagulation values. However, it is much more expensive than regular heparin ($6-8/day) so it has not been used extensively.
The final option for prevention of new clots is a medication called warfarin. This is an oral medicine that is a very strong anticoagulant. It works by preventing the liver from making functional vitamin K-dependant coagulation factors (II, VII, IX and X). It takes three to five days to begin to work. The medication is inexpensive, but requires frequent monitoring of the coagulation times (prothrombin time- PT) in order to make sure the dose is in the right area. Too high of a dose may cause life-threatening bleeding and too low of a dose will be ineffective. Warfarin is an excellent anticoagulant, but requires a patient dog, family member and veterinarian in order to ensure treatment success.
Unfortunately, to date the prognosis for seriously affected Greyhounds seen at the Foster Hospital for Small Animals has been very poor with no long-term survivors. Affected dogs may die from their disease or may be euthanized for humane reasons due to inability to walk and adequately control pain. There remain many questions to answer and problems to solve.
It remains important to try to both identify affected animals early so that treatment can be begun and also identify why individual dogs, and particularly Greyhounds, seem to be developing this condition. Ideally, with a good understanding of why the clots develop we will be able to prevent dogs from discomfort and death.
How you can help
Because aortic thromboembolism is still a rare disease in dogs, it is difficult to be able to fully identify the incidence of disease in Greyhounds. If you have a Greyhound with hind limb lameness without an identifiable orthopedic condition, please make sure (or have your veterinarian assess) that the pulses in the femoral arteries are strong. We would also like to be able to describe the Greyhounds that have been affected and to try to determine what tests and therapies have been effective for a large population of dogs. If you have or know a dog that has been affected with aortic thromboembolism, please consider sending a copy of his or her medical record to us and answering the following questions.
1)What is your dog’s name, age and sex ?
2)Did your dog have a racing career? If so, for how long?
3)What is the length of time your dog has lived with you?
4)Does your dog have any other medical problems?
5)Please list any medications (including heartworm preventative and flea/tick preventative) your dog has received.
6)Did your dog get any treatment with aspirin, prednisone, rimadyl or etogesic(Or any other anti-inflammatory medicine) for this problem?
7)How long did your dog show evidence of problems with the hind legs before diagnosis?
8)How was the aortic thromboembolism identified?
9)Please send (or have your veterinarian send) copies of blood testing or interpretation of xrays, ultrasound, echocardiogram etc.
10)Were any treatments used?
11)Were these treatments successful?
12)Any other comments or observations?
13)Your name and your veterinarian name if you would be available for more questions.
Please send information to: Elizabeth Rozanski DVM, Tufts University, 200 Westboro Road, North Grafton, MA 01536 or firstname.lastname@example.org
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