Inherited blood disorders

Immune-mediated hemolytic anemia (IMHA)

roblib — Fri, 26 Feb 2010 15:58:40 +0000

What is ... ?:

Normally red blood cells live about 4 months in dogs. As the cells age, they are removed and destroyed by other cells that are part of the immune system. New red blood cells are produced in the bone marrow at a rate that matches the destruction of older cells. In IMHA, the immune system destroys red blood cells prematurely, faster than the rate at which new ones can be produced. The name says it all - anemia (reduced red blood cells) caused by hemolysis (destruction) by the body's own immune system.

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How is ... inherited?:

The condition may occur in any breed, but it is seen most commonly in the breeds listed below.

What breeds are affected by ... ?:

What does ... mean to your dog & you?:

IMHA can occur at any age, but is most common in middle-aged female dogs. It may be mild and hardly noticeable, or it may be sudden in onset and severe. Usually the kinds of signs you see are vague - such as poor appetite, weakness, listlessness, lack of energy. You may notice that your dog's gums are pale, or they may be yellowish due to jaundice as a result of the breakdown of red blood cells. Your pet may have a rapid heart beat and rapid breathing. One form of IMHA(cold agglutinin disease) causes circulation problems in cooler peripheral parts of the body, so the ear or tail tips, or feet may become infected and dark in colour. Reduced levels of circulating red blood cells mean reduced oxygen going to the tissues. Most dogs that die with this condition do so in the first few days due to kidney, liver, or heart failure, or because of a bleeding problem.

How is ... diagnosed?:

Your veterinarian will suspect that your dog is anemic through physical examination. S/he will do some blood tests to find the cause. The diagnosis of IMHA is made by identifying antibodies on the surface of the red blood cells, and ruling out other causes of anemia.

For the veterinarian: In IMHA, the immune system destroys rbcs by coating them with immunoglobulin or complement. In most cases of IMHA, the rbcs are coated with incomplete (ie don't agglutinate rbcs in saline) and warm-type ( ie. react optimally at 35 - 40°C) autoantibodies, mostly IgG. Hemolysis may be intra- or extravascular (mostly in the spleen). Cold antibodies react optimally below 30°C, and are virtually always IgM. These may cause rbc agglutination or hemolysis in the body periphery (ear tips, paws, tail).

CBC: The common picture is a highly regenerative anemia, sometimes with a dramatic reactive leukocytosis (neutrophilia and left shift) +/- thrombocytopenia. Hallmarks of regenerative anemia include spherocytosis, autoagglutination, polychromasia, anisocytosis, and reticulocytosis. The absence of reticulocytosis does not preclude a diagnosis of IMHA; this may be due to recent onset (less than 3 days) or destruction of young rbcs in the bone marrow. Bone marrow aspiration should be done if there is a persistent reticulocytopenia, to rule out other primary bone marrow disorders.

Biochem. profile: There may be minimal to moderate changes in liver enzyme levels depending on the acuteness and severity of the hemolytic crisis. With intravascular hemolysis, you may see hemoglobinemia and hemoglobinuria.

Saline autoagglutination is diagnostic of IMHA. Mix 1 drop of anticoagulated whole blood with 1 drop physiologic saline on a microscope slide. If enough antibody molecules are present on the rbcs, you will see agglutination (not to be confused with rouleaux formation, which will quickly disperse unlike autoagglutination). The DAT (Direct Antiglobulin Test, or Coomb's test) is used to detect antibodies on rbcs, when levels are too low to cause autoagglutination. The test is positive in about 60% of cases. The DAT may be negative due to a low number of immunoglobulin molecules on the red cell, problems with the test, immunosuppressive treatment, or an incorrect diagnosis.

Dogs with IMHA are in a hypercoaguable state with increased risk of developing DIC or pulmonary thromboembolism.

How is ... treated?:

Unfortunately, dogs severely affected with this condition may die even with the best treatment. This mostly occurs in the first few days due to kidney, liver, or heart failure, or because of a bleeding problem. The goals of treatment are (1) to slow the destruction of red blood cells (rbcs), and (2) to support the dog while the red blood cell level has a chance to recover.
1) Immunosuppressive therapy with corticosteroids is given to slow rbc destruction, initially at high doses which are gradually tapered over several weeks as rbc levels stabilize and begin to rise again. If rbc levels continue to fall despite steroid therapy, other immunosuppressive drugs may be given.
2) Blood transfusions are needed when the rbc level is critically low. Although the new cells will also be destroyed at the same rate, the transfusion will buy some time for the dog while his/her own blood cell levels are recovering.
Dogs that recover from an episode of IMHA may experience future relapses.

For the Veterinarian: With severe IMHA (intravascular hemolysis or autoagglutinating or unresponsive to glucocorticoids alone), more aggressive therapy (cytotoxic agents combined with corticosteroids) may include azathioprine or cyclosporine. Danazol (an attenuated androgen) stabilizes red cell membranes and is used as an adjunctive therapy with corticosteroids.
Packed rbcs should be given based on the hematocrit and the condition of the dog to maintain adequate oxygen-carrying capacity. Prophylactic heparin may be given to reduce the risk of thromboembolism.

Breeding advice:

Dogs who have been diagnosed with IMHA should not be used for breeding, and it is preferable to avoid breeding their close relatives as well.

Resources:

Miller E. Immune-mediated hemolytic anemia. In: Bonagura JD, Twedt DC, eds. Kirk's Current Veterinary Therapy XIV. Missouri: Saunders Elsevier, 2009:266-271.
O'Toole T. Immune-mediated hemolytic anemia. In: Côté E, ed. Clinical Veterinary Advisor Dogs and Cats. Missouri: Mosby Elsevier, 2007:66-68.

Coagulation (bleeding) disorders

roblib — Tue, 16 Mar 2010 14:10:18 +0000

What is ... ?:

Normally the body responds to an injury that causes bleeding through a complex defence system. This consists of local changes in the damaged blood vessels, activation of blood cells called platelets, and the coagulation (clotting) process. Most inherited bleeding disorders are the result of abnormal platelet function or a deficiency in one or more of the factors involved in the blood clotting system. The most serious and common inherited coagulation disorders in dogs are hemophilia(deficiency of factor VIII or IX) and von Willebrand's disease (lack of von Willebrand factor).

Other coagulation disorders are discussed here. These abnormalities of specific clotting factors are much less common and usually cause a milder type of bleeding disorder. Inherited deficiencies of factors I (fibrinogen), II (prothrombin), VII (proconvertin), X (Stuart factor), XI (PTA), and XII (Hageman factor) have been identified, most commonly in purebred dogs but also in mixed breed dogs.

How is ... inherited?:

Other than hemophilia, disorders of clotting factors are inherited as autosomal traits, primarily autosomal recessive. These uncommon deficiencies have been identified in the following breeds: Factor I (hypofibroginemia) - Saint Bernard; factor II - boxer; factor VII - beagle; factor X - American cocker spaniel, Jack Russell terrier; factor XI - springer spaniel, Great Pyrenees, Kerry blue terrier; factor XII - miniature poodle

What breeds are affected by ... ?:

What does ... mean to your dog & you?:

Factor XII deficiency generally causes no problems and is only discovered if coagulation testing is done.

Deficiencies of factor VII or XI tend to cause mild disease. You may notice that your dog bruises easily or has nosebleeds. There is often prolonged bleeding after surgery or trauma and, with major surgical procedures or trauma, bleeding may be severe.
Deficiencies of factor I, II or X are rare; however they cause severe bleeding problems. Factor X deficiency causes stillbirths or "fading puppies" that only live for a few weeks.

How is ... diagnosed?:

A deficiency of factor XII usually causes few problems and is only discovered incidentally if coagulation testing is done. Deficiencies of factor VII or XI may only be discovered when surgery is performed or if your dog is in an accident. In both these cases there will likely be increased bleeding which can be slow in onset and difficult to control, and your veterinarian will suspect a coagulation disorder. Special screening tests are required to diagnose the specific clotting factors involved.

For the veterinarian:
SCREENING TESTS: The mucosal bleeding time is normal for all factor deficient patients, although there may be rebleeding. Coagulation screening tests (citrate sample) will localize the defect further to the extrinsic, intrinsic, or common pathway. Definitive diagnosis requires an assay for specific factors. Specific factor assays can also be used to screen for carriers (heterozygotes), who have a reduced amount of normal factor activity. (Consult your diagnostic laboratory for specific information about sample collection and submission.)

CLINICAL: With factor XI deficiency in particular, onset of bleeding after surgery or trauma may be delayed up to 48 hours, and hemorrhage may be severe.

How is ... treated?:

A dog with a factor XI deficiency may require one or more blood transfusions if there is severe bleeding after surgery or an accident.

For the veterinarian:
If there is a severe bleeding episode, administer fresh or fresh-frozen plasma. Transfused factors have a relatively short half-life, so plasma may need to be transfused every 8 to 12 hours until the bleeding stops. Fresh whole blood may be used but it must be carefully cross-matched to prevent future transfusion reactions. If a dog has been diagnosed with a factor XI deficiency, fresh or fresh-frozen plasma should be administered before any major surgery.

FOR MORE INFORMATION ABOUT THIS DISORDER, PLEASE SEE YOUR VETERINARIAN.

Breeding advice:

Affected dogs should not be used for breeding, and parents and siblings should be carefully screened for these traits. It is possible to detect carriers, based on the levels of factor activity. Many cocker spaniel breeders for example, have had their breeding dogs tested for factor X deficiency, reducing the frequency of this harmful gene in the cocker spaniel population.

Resources:

Brooks MB. 1998. Hereditary bleeding disorders. ACVIM-Proceedings of the 16th Annual Veterinary Forum:424-426. This reference has information on diagnosis/screening tests for specific coagulopathies, genetic counselling, and carrier detection.

Brooks MB. Hemophilias and other hereditary coagulation factor deficiencies. In: Côté E, ed. Clinical Veterinary Advisor Dogs and Cats. Missouri: Mosby Elsevier, 2007:482-3.

Sargan DR. Coagulation disorders in IDID - Inherited diseases in dogs:web-based information for canine inherited disease genetics. Mamm Genome. 2004 Jun;15(6):503-6.

Canine cyclic hematopoiesis

roblib — Thu, 18 Mar 2010 14:37:04 +0000

What is ... ?:

This disorder of the immune system occurs in gray collies. Puppies are usually smaller and weaker than their littermates and by 8 to 12 weeks of age they develop clinical signs such as fever, diarrhea or joint pain, or other signs associated with eye, respiratory, or skin infections.

The disorder is caused by an abnormality of the stem cells in the bone marrow, from which all blood cells develop. The result is a cyclic fluctuation in blood cell numbers, primarily neutrophils, which are very important in fighting infections. Every 10 to 12 days, the number of neutrophils drops dramatically, and then rebounds. There is increased susceptibility to infection corresponding to the dip in neutrophil numbers. As well, the normal activity of the neutrophils is impaired. These dogs are also prone to bleeding episodes due to the drop in platelet numbers.

How is ... inherited?:

The mode of inheritance is autosomal recessive. Both parents must carry the abnormal gene for the offspring to be affected.

What breeds are affected by ... ?:

Collie (rough and smooth)

What does ... mean to your dog & you?:

This is a very serious disorder. These dogs are subject to severe recurring bacterial infections, primarily of the respiratory or gastrointestinal tract. Even with the best of care, affected dogs rarely live beyond 2 or 3 years of age.

How is ... diagnosed?:

Affected dogs have a light silver gray, possibly mixed with light beige, hair coat and a characteristic light coloured nose. Pups usually experience clinical illness by 8 to 12 weeks of age and are brought to the veterinarian at that time, if the breeder does not recognize the defect before then.

The disorder is diagnosed based on the cyclic fluctuation in blood cell numbers, as well as the characteristic coat coloration.

For the veterinarian:
Cyclic neutropenia occurs every 10 to 12 days, persists 2 to 4 days, and is followed by a rebound neutrophilia (during which infections resolve). Other hematologic abnormalities include non-regenerative anemia, and cyclic reticulocytosis, monocytosis, and thrombocytosis. Even with optimal care, affected animals usually die before 2 to 3 years of age due to chronic recurring infections and/or hepatic or renal failure associated with amyloidosis.

How is ... treated?:

The only practical treatment is supportive care and antibiotics during neutropenic episodes. Without supportive care, pups usually die before 6 months of age. Even with the best of care, including very close monitoring and antibiotics to counteract the variety of infections, these dogs usually die before 2 or 3 years of age.
Bone marrow transplant and gene therapy have been attempted on an experimental basis.
FOR MORE INFORMATION ABOUT THIS DISORDER, PLEASE SEE YOUR VETERINARIAN.

Breeding advice:

As a rule, parents and littermates of affected dogs should not be used for breeding, to avoid perpetuating this lethal defect.
HealthGene Laboratory offers a DNA-based test for canine cyclic hematopoiesis that identifies normals, carriers (heterozygous), and affected dogs, which will assist with judicious breeding.

Resources:

Raskin R. Hematologic disorders – cyclic hematopoiesis. In: Schaer M, ed. Clinical Medicine of the Dog and Cat. London, UK: Manson, 2010:261.
Sargan DR. Cyclic hematopoiesis in IDID - Inherited diseases in dogs:web-based information for canine inherited disease genetics. Mamm Genome. 2004 Jun;15(6):503-6.

Hemophilia

roblib — Thu, 18 Mar 2010 14:54:19 +0000

What is ... ?:

Hemophilia is a bleeding disorder of varying severity that is due to a deficiency in specific clotting factors. Normally the body responds to an injury that causes bleeding through a complex defence system. This consists of local changes in the damaged blood vessels, activation of blood cells called platelets, and the coagulation (clotting) process. Most inherited bleeding disorders are the result of abnormal platelet function or a deficiency in one or more of the factors involved in the blood clotting system.

Hemophilia is the most common inherited coagulation factor deficiency. Hemophilia A is a result of a deficiency of factor VIII, and hemophilia B of factor IX. Hemophilia A is more common than hemophilia B, and varies in severity depending on the level of factor VIII activity. Hemophilia B is often a severe bleeding disorder.

How is ... inherited?:

Hemophilia is an X-linked,recessive disorder. It is one of the few sex-linked traits in dogs. Because males have only 1 X chromosome, a male dog is either affected or clear of the defect. Females, with 2 X chromosomes, may be affected (abnormal gene on both chromosomes), clear, or a carrier with no clinical signs (one gene affected). In effect, the disease is carried by females but affects mostly males. The disease occurs in many different breeds and in mixed breed dogs as well. The German shepherd is the breed most commonly affected.

What breeds are affected by ... ?:

What does ... mean to your dog & you?:

Dogs with mild forms of hemophilia may experience few or no signs, and may never require treatment until/unless surgery or trauma is followed by excessive bleeding.
Where hemophilia is more severe, you may see signs of a problem at a fairly early age. Your pup may have prolonged bleeding associated with the loss of baby teeth, or unexplained areas of bleeding under the skin. Bleeding into muscles or joints will often cause lameness.

Once the condition is diagnosed, your veterinarian will discuss ways to manage this lifelong problem. These include being alert for signs of bleeding episodes in your dog, and tips on housing and maintenance so as to minimize risks of bleeding. Periodic blood transfusions will generally be required. Unfortunately, dogs with severe hemophilia often die or are euthanized because of recurrent or uncontrollable bleeding problems.

How is ... diagnosed?:

The clinical signs associated with hemophilia vary widely, based on the severity of the bleeding disorder and where in the body the bleeding occurs. Because this is a sex-linked disorder, dogs with hemophilia are almost always male. Affected dogs are commonly brought to the veterinarian for problems such as bloody diarrhea that is difficult to control, areas of bleeding under the skin, or lameness (due to bleeding into muscles or joints). Bleeding under the skin or into the muscle may occur after routine vaccination, or there may be prolonged or severe bleeding at surgery (such as when your dog is neutered.) Other less common problems include respiratory difficulties due to bleeding into the chest or around airways, or weakness, paralysis, or even sudden death due to bleeding into the brain or spinal cord.

Once a bleeding disorder is suspected, specialized laboratory tests are carried out to diagnose the specific disorder. If your pup is diagnosed with hemophilia, it is important that you inform the breeder so that he or she can have your dog's parents tested. (The mother is likely a carrier and the father free of the defect.)

For the veterinarian:
CLINICAL: Signs are highly variable and often non-specific: unthriftiness, acute blood loss anemia, unexplained sub-cutaneous masses, hematomas (often at injection sites), refractory bloody diarrhea. Other signs depend on the local physiologic impact of hemorrhage: for example bleeding into the brain or around nerve trunks will cause neurologic signs, and bleeding around airways or into the pleural cavity will cause respiratory signs. Lameness is commonly associated with hemorrhage into muscles or joints, especially in larger breeds.

LABORATORY: normal PT (prothrombin time) and prolonged aPTT (activated partial thromboplastin time); definitive diagnosis requires a specific assay for factors VIII and IX. Factor activity will be markedly decreased. Specific factor assays are also required to screen for female carriers (heterozygotes), who usually have about 40 to 60% of normal factor activity. Consult your diagnostic laboratory for specific information about sample collection and submission.

How is ... treated?:

There is no cure for this disorder. Mildly affected dogs may never require treatment, or only after surgery or trauma.

With more severe hemophilia, your dog will require periodic transfusions when bleeding occurs, to replace the deficient coagulation factor activity. Strict cage rest is important along with transfusion, to decrease further hemorrhage.

For the veterinarian:
Administer fresh plasma, fresh frozen plasma, or cryoprecipitate (factor VIII) or cryosupernatant (factor IX) plasma. Transfused factors have a relatively short half-life so plasma may need to be transfused every 8 to 12 hours until the bleeding stops. Fresh whole blood may be used but it must be carefully cross-matched to prevent future transfusion reactions.

Breeding advice:

Because hemophilia is a sex-linked recessive trait and the carrier state can be detected by testing, this disorder can be controlled. German shepherd females and females from lines of other breeds where hemophilia has been diagnosed, should be tested for the carrier state. Males used for breeding should be screened for the disorder.

FOR MORE INFORMATION ABOUT THIS DISORDER, PLEASE SEE YOUR VETERINARIAN.

Resources:

Brooks,M. 1998. Hereditary bleeding disorders. ACVIM-Proceedings of the 16th Annual Veterinary Medical Forum: 424-426.

Brooks MB. Hemophilias and other hereditary coagulation factor deficiencies. In: Côté E, ed. Clinical Veterinary Advisor Dogs and Cats. Missouri: Mosby Elsevier, 2007:482-3.

Sargan DR. Coagulation disorders in IDID - Inherited diseases in dogs:web-based information for canine inherited disease genetics. Mamm Genome. 2004 Jun;15(6):503-6.

Histiocytoma

roblib — Thu, 18 Mar 2010 15:05:14 +0000

What is ... ?:

Histiocytomas are common benign (non-invasive, non-recurrent) tumours in young dogs.

What breeds are affected by ... ?:

What does ... mean to your dog & you?:

These small growths usually occur singly on the head, limbs or ears, most often in dogs who are less than 2 years of age. These growths won't trouble your dog unless they are itchy.

How is ... diagnosed?:

The tumours are small (less than 3 cm), domed or flat, red, and may be ulcerated. They may or may not be itchy. Definitive diagnosis is by histopathologic examination of the tumour after removal. It is important to differentiate histiocytoma from other histiocytic diseases.

How is ... treated?:

Surgery or cryosurgery (freezing) can be used to remove the tumour. Most of these tumours will disappear on their own after a few months.

FOR MORE INFORMATION ABOUT THIS DISORDER, PLEASE SEE YOUR VETERINARIAN.

Resources:

Woods J, Latimer K, Bain P. Canine cutaneous histiocytoma

Histiocytosis

roblib — Thu, 18 Mar 2010 15:31:13 +0000

What is ... ?:

Histiocytic syndromes are a complex group of disorders which overlap. They result from an accumulation of histiocytes - cells which arise from the bone marrow and circulate throughout the body as part of the normal defense system. Cutaneous histiocytosis is a benign form of histiocytosis in which there are small skin lesions around the head and neck which may come and go, and may or may not respond to treatment. Dogs with systemic histiocytosis also have head and neck lesions, with lymph nodes affected as well. In malignant histiocytosis, skin masses are uncommon; instead, internal organs are affected (eg. spleen, liver, lungs, bone marrow).Unfortunately, malignant and systemic histiocytosis are characterized by rapid and invasive spread, with poor response to treatment.

How is ... inherited?:

The disorder has a polygenic mode of inheritance in the Bernese mountain dog. The disorder is also more common in the other breeds listed below.

What breeds are affected by ... ?:

What does ... mean to your dog & you?:

In both systemic and malignant histiocytosis, signs of illness include loss of appetite, weight loss, and lethargy. In systemic histiocytosis, there are skin lesions (crusting, firm nodules, ulcers) but these are uncommon in malignant histiocytosis. Both affect middle-aged to older dogs, while cutaneous histiocytosis occurs in younger dogs. There may be periods of remission with systemic histiocytosis, but ultimately the histiocytes infiltrate other organ systems especially the lungs, liver, spleen, bone marrow, and lymph nodes. Malignant histiocytosis is a rapidly progressive and invasive disorder, which commonly metastasizes to the lungs.

How is ... diagnosed?:

The clinical signs of this disorder vary depending on where metastasis of abnormal cells occurs. Tumours in the lungs are common, causing respiratory signs such as coughing and shortness of breath. Your veterinarian will likely suspect a tumour based on clinical signs, radiology, and blood tests; he or she will submit tissue samples to a pathologist for histopathologic examination to determine the type of tumour.

How is ... treated?:

Malignant histiocytosis spreads rapidly and metastasis is generally present at the time of diagnosis, so that surgical treatment is ineffective. Dogs with systemic histiocytosis may experience periods of remission, or the disease may progress rapidly. Various types of chemotherapy have been tried for both types of histiocytosis, but with little success. Your veterinarian will work with you to keep your dog as comfortable as possible, until the quality of life deteriorates to the point where euthanasia is the best treatment option.

For the veterinarian:

CLINICAL: most common in Bernese mountain dogs; see anorexia, weight loss, lethargy, lymphadenopathy, lameness if joint or bony involvement, plus signs associated with metastasis (commonly respiratory, also gastrointestinal or nervous); with systemic histiocytosis, you will also see multiple cutaneous plaques, ulcers, nodules and papules, which can be anywhere but are seen primarily on face and limbs.

RADIOLOGY: commonly see thoracic abnormalities such as single or multiple masses, hilar lymphadenopathy, pleural effusion; may see hepato or splenomegaly.

LABORATORY: hematology may be normal, or there may be regenerative or non-regenerative anemia; may see elevated liver enzymes; fine needle aspirates of accessible masses or lymph nodes may show fairly normal cells with systemic histiocytosis (cf. malignant histiocytosis).

Breeding advice:

Because this invariably fatal disorder generally does not develop until the dog is middle-aged or older, it can be hard to identify parents that carry the trait. It is very important that the veterinarian and/or owner inform the breeder when this disorder has been diagnosed, so that he or she can modify the breeding programme accordingly, to limit the spread of the harmful gene(s) in the Bernese mountain dog population.

FOR MORE INFORMATION ABOUT THIS DISORDER, PLEASE SEE YOUR VETERINARIAN.

Resources:

Sargan DR. Histiocytosis. In IDID - Inherited diseases in dogs:web-based information for canine inherited disease genetics.
Selting K. Histiocytic diseases. In: Côté E, ed. Clinical Veterinary Advisor Dogs and Cats. Missouri: Mosby Elsevier, 2007:523-525.

Immune-mediated thrombocytopenia

roblib — Mon, 22 Mar 2010 17:07:43 +0000

What is ... ?:

Thrombocytopenia means a reduction in platelets (thrombocytes). Platelets (one of the cell types in the blood) play an important role in the clotting process; thus the main result of a decrease in platelets is increased bleeding - for example, nosebleeds.

In immune-mediated thrombocytopenia (IMT), the reduction happens because there is increased destruction of platelets by the body's own immune system, at a rate faster than they are produced in the bone marrow. IMT may be secondary to some other process (such as an infection, tumour, or drug reaction) or it may be primary, meaning that no other causative factor can be found. It is more common in certain breeds, suggesting an inherited genetic susceptibility. IMT may occur by itself or with other conditions like systemic lupus erythematosus and immune-mediated hemolytic anemia.

How is ... inherited?:

unknown. It is more common in female dogs than in males.

What breeds are affected by ... ?:

What does ... mean to your dog & you?:

The main problem for dogs affected by IMT is increased bleeding. Your dog may have nosebleeds, bruising on the gums or skin, and/or blood in the stool or urine (seen as a darker than normal colour). Your dog may also appear weak or lethargic.

Many dogs with IMT experience only one episode of thrombocytopenia, and respond well to treatment. Some dogs will have occasional relapses, which may be associated with stressors such as another illness, or travel. Unfortunately some dogs with this disorder die acutely because of severe internal bleeding.

How is ... diagnosed?:

With signs of increased bleeding, your veterinarian will do a CBC (complete blood count), which will show a dramatic drop in platelet numbers. Bleeding does not occur until the platelet count is below 25,000/µl of blood. (Normal levels are above 200,000).

Then it is a matter of ruling out other possible causes of thrombocytopenia, which are many. Any disorder that causes increased widespread excessive bleeding will cause a drop in platelets, simply because they are being used up (consumptive coagulopathy).

How is ... treated?:

Corticosteroids are given to slow platelet destruction, initially at high doses which are gradually tapered as platelet levels stabilize and begin to rise again. The response to treatment is usually good. If platelet levels continue to fall despite steroid therapy, other immunosuppressive drugs can be given.Blood or platelet-rich plasma transfusions may be required, to supply oxygen to the tissues and to control bleeding.

Aftyer recovery, ongoing monitoring is needed to identify any relapse early, and stressful circumstances should be avoided where possible.

For the veterinarian:

CBC (with manual differential) will usually be normal unless bleeding causes anemia. A peripheral blood smear should be evaluated for platelet clumping, size and morphology. Coagulation profiles (also usually normal with ITP) should be done to rule out intrinsic and extrinsic coagulation defects that may be causing a general consumption of peripheral platelets. Other differentials for thrombocytopenia include reduced production secondary to lymphoma, myeloproliferative disease, and preleukemic states. Bone marrow cytology is usually not necessary unless there are other abormalities; increased numbers and immaturity of megakaryocytes indicate a regenerative response, in contrast to an unresponsive or preregenerative bone marrow. Regeneration should be evident within 3 to 5 days of an acute thrombocytopenic episode.

The diagnosis of primary IMT is made if no causes of secondary IMT can be found, which is most often the case. Secondary IMT may be caused by certain drugs (cephalosporins, gold compounds and others), neoplasia, infectious diseases (eg. canine distemper), or other immune-mediated disorders such as SLE or IMHA.

Breeding advice:

Dogs that have had an episode of immune-mediated thrombocytopenia should not be used for breeding.

FOR MORE INFORMATION, PLEASE SEE YOUR VETERINARIAN.

Resources:

Neel JA, Birkenheuer AJ, Grindem CB. Thrombocytopenia. In: Bonagura JD, Twedt DC, eds. Kirk's Current Veterinary Therapy XIV. Missouri: Saunders Elsevier, 2009:281-287.
Stone M. Immune-mediated thrombocytopenia. In: Côté E, ed. Clinical Veterinary Advisor Dogs and Cats. Missouri: Mosby Elsevier, 2007:1079-1080.
Sargan DR. Thrombocytopenia. In IDID - Inherited diseases in dogs:web-based information for canine inherited disease genetics.

Lymphedema

roblib — Mon, 22 Mar 2010 17:27:59 +0000

What is ... ?:

Lymph is a clear watery fluid that is collected from tissues throughout the body and returned to the blood by way of the lymphatic vessels, as part of normal circulation. In lymphedema there is abnormal lymph flow, so that lymph fluids accumulate and cause swelling in the affected tissue.

Primary or inherited lymphedema is caused by abnormal development of the lymph vessels or nodes and has been reported in the breeds listed below. Secondary lymphedema can occur in any breed if there is obstruction of lymph vessels due to tumours, inflammation, surgery, etc.

How is ... inherited?:

In some breeds, the mode of inheritance has been shown to be autosomal dominant with variable expressivity.

What breeds are affected by ... ?:

What does ... mean to your dog & you?:

The hind legs are most commonly affected, although front legs, abdomen, tail and ears can be affected too. The skin looks normal but has a thickened spongy feel, and if you press it, your fingers will leave dents.

Skin that is swollen due to lymphedema is susceptible to bacterial infection and delayed healing after injury, but otherwise your dog will be generally healthy.

How is ... diagnosed?:

Diagnosis is made based on physical examination and tests to rule out other causes of edema.

How is ... treated?:

Mild cases of lymphedema may come and go, or persist without any adverse consequences for your dog's health. Soft compressive bandages may be required to reduce the swelling due to fluid (lymph) build-up, and antibiotics will be required in the case of infection.

For the veterinarian:

Primary lymphedema is most commonly seen in puppies or young dogs as pitting, non-painful edema in the pelvic limbs. Pain usually indicates secondary infection.
Rule out other causes of obstructive, inflammatory, and hypoproteinemic edema.

Breeding advice:

Affected animals and their close relatives should not be bred.
FOR MORE INFORMATION ABOUT THIS DISORDER, PLEASE SEE YOUR VETERINARIAN.

Resources:

Bonagura J. Lymphedema. In: Côté E, ed. Clinical Veterinary Advisor Dogs and Cats. Missouri: Mosby Elsevier, 2007:648-650.

Phosphofructokinase (PFK) deficiency

roblib — Mon, 22 Mar 2010 17:50:09 +0000

What is ... ?:

The enzyme PFK is important in energy metabolism in red blood cells and in skeletal muscle during intense exercise. PFK deficiency is an inherited disorder that causes premature breakdown (hemolysis) of red blood cells, and a reduced tolerance for exercise. Affected dogs have chronic mild anemia with intermittent bouts of acute hemolysis, often associated with intense exercise, overheating or prolonged barking.

How is ... inherited?:

This is an autosomal recessive trait which means both parents of an affected dog are carriers of the disorder. Carriers have about one half normal enzyme activity in red blood cells and muscle tissue, and are clinically unaffected.

What breeds are affected by ... ?:

What does ... mean to your dog & you?:

Affected dogs have a persistent mild anemia (low levels of red blood cells) for which they are generally able to compensate. Intermittently they will have acute episodes of red blood cell breakdown (hemolysis), when they become lethargic and weak. This is usually associated with intense exercise or excessive barking or panting. Their mucous membranes (eg. gums) are pale or jaundiced and they usually run a high fever. You may notice the urine is brown due to the excretion of blood breakdown products. At these times your dog will require veterinary attention.

Dogs with this condition can have a normal life span. Management of this condition requires avoidance of stress, strenuous exercise, overheating and over excitement.

How is ... diagnosed?:

Based on clinical examination and blood tests, your veterinarian will diagnose hemolytic anemia (low levels of red blood cells due to increased breakdown) in your dog. Further tests will be required to diagnose this specific condition.

How is ... treated?:

There is no specific treatment for this disorder, other than supportive care during an episode of bleeding (which may require a blood transfusion). Carrier and affected dogs should be removed from the breeding population.

The condition can be well-managed, and your veterinarian will discuss this with you. You will need to be alert for signs associated with increased intravascular hemolysis (red cell breakdown), such as weakness, lethargy, pale or jaundiced mucous membranes, or brownish urine. It is also important to avoid stressful situations, strenuous exercise, excitement that will cause a great deal of barking, and high environmental temperatures.

For the veterinarian:

CLINICAL: persistent compensated hemolytic anemia (PCV at or near normal) with intermittent hyperventilation-induced hemolytic crises with (usually mild) exertional myopathy, poor exercise tolerance; during hemolytic crisis, signs may include lethargy, weakness, hepatosplenomegaly, muscle wasting, pale or icteric mucous membranes, pyrexia (to 41 degrees Celsius).

LABORATORY: A specific genetic test can identify carriers and affected animals at any age (see reference below). Affected and carrier dogs can also be identified based on PFK activity in blood samples. Check with your clinical pathology lab for requirements for sample submission.

Breeding advice:

Because this is an autosomal recessive trait, both parents of affected dogs carry the defective gene. Neither affected (homozygous) or carrier dogs (heterozygous) should be used for breeding. There is a DNA test that can identify carrier dogs at any age (see reference below). Many affected and carrier dogs have already been removed from the breeding population.

Resources:

Harvey, J.W. 1995. Congenital hemolytic anemias and methemoglobinemias. ACVIM-Proceedings of the 13th Annual Veterinary Medical Forum: 37-40.

Henderson A. Anemia, Hemolytic. In: Côté E, ed. Clinical Veterinary Advisor Dogs and Cats. Missouri: Mosby Elsevier, 2007:64-66.

Sargan DR. Phosphofructokinase deficiency. In IDID - Inherited diseases in dogs:web-based information for canine inherited disease genetics.

Genetic testing (English and French) Labgenvet: www.labgenvet.ca

www.vetgen.com - information on genetic testing available

Pyruvate kinase (PK) deficiency

roblib — Mon, 29 Mar 2010 14:26:31 +0000

What is ... ?:

Pyruvate kinase is a key enzyme in energy metabolism in red blood cells. This inherited disorder causes a deficiency in this enzyme which results in a marked shortening of the life span of red blood cells, and therefore a severe hemolytic anemia - low red blood cell numbers due to cell breakdown.

How is ... inherited?:

What breeds are affected by ... ?:

What does ... mean to your dog & you?:

Dogs with PK deficiency usually show signs by 4 months to 1 year of age. Because of the severe anemia (low levels of red blood cells), affected dogs are slow to grow, and show a mild weakness and a low tolerance for exercise. Unfortunately these dogs also gradually develop changes in their bones, specifically replacement of the bone marrow with fibrous tissue, and hardening or abnormal density of bone (called myelofibrosis and osteosclerosis). Dogs with pyruvate kinase deficiency usually die before 4 years of age, due to bone marrow failure and/or liver disease.

How is ... diagnosed?:

Signs of anemia include pale mucous membranes (your dog's gums for example), an increased heart rate and a reduced tolerance for exercise. Your veterinarian will do blood tests to determine the cause of the anemia which in this disorder is due to increased red blood cell breakdown. Further tests will be required to diagnose this specific condition as the cause of the hemolytic anemia.

How is ... treated?:

There is no specific treatment for this disorder, other than supportive care as necessary.

For the veterinarian:

HEMATOLOGY: persistent, severe (PCV 12 to 26%), highly regenerative anemia which becomes less responsive as the dog ages.
DIAGNOSIS: Erythrocytes from affected dogs completely lack the normal R-type PK isoenzyme, but they do have an abnormal M-type PK isoenzyme. Thus special laboratory tests are required to diagnose a PK deficient dog, rather than simply measuring total PK activity. Carrier dogs, with half normal activity, can also be identified. Check with your clinical pathology lab for requirements for sample submission. A DNA diagnostic test has been developed for Basenjis and West Highland white terriers which can identify carriers and affected animals at any age (see reference below).
OTHER SIGNS: hepatosplenomegaly, progressive myelofibrosis and osteosclerosis, +/- terminal liver disease with hemochromatosis and cirrhosis.

Breeding advice:

Resources:

Harvey, J.W. 1995. Congenital hemolytic anemias and methemoglobinemias. ACVIM-Proceedings of the 13th Annual Veterinary Medical Forum: 37-40.
Henderson A. Anemia, Hemolytic. In: Côté E, ed. Clinical Veterinary Advisor Dogs and Cats. Missouri: Mosby Elsevier, 2007:64-66.
Sargan DR. Pyruvate kinase deficiency. In IDID - Inherited diseases in dogs:web-based information for canine inherited disease genetics.
vetGen - information on genetic testing available (Basenjis and West Highland white terriers)

Rare red blood cell abnormalities

roblib — Mon, 29 Mar 2010 14:29:21 +0000

Resources:

Giger U, Smith BF, Rajpurohit WP. 1992. Inherited erhythrocyte disorders. ACVIM- Proceedings of the 10th Annual Veterinary Medical Forum:142-145.
Harvey JW. 1995. Congenital hemolytic anemias and methemoglobinemias. ACVIM-Proceedings of the 13th Annual Veterinary Medical Forum:37-40.
There is information on some of these disorders in: Sargan DR. IDID - Inherited diseases in dogs:web-based information for canine inherited disease genetics.

Pyruvate kinase deficiency and phosphofructokinase deficiency are two clinically important red blood cell disorders that are discussed elsewhere in this database.

von Willebrand's disease

roblib — Tue, 04 May 2010 17:17:24 +0000

What is ... ?:

Von Willebrand's disease (vWD) is a common, usually mild, inherited bleeding disorder in people and in dogs. It is caused by a lack of von Willebrand factor (vWF), which plays an essential role in the blood clotting process.

Normally the body responds to an injury causing bleeding through a complex defense system. This consists of local changes in the damaged blood vessels, activation of blood cells called platelets, and the coagulation process. A reduction in von Willebrand factor leads to abnormal platelet function and prolonged bleeding times. Affected dogs are prone to bleeding episodes, such as nose bleeds, and generally experience increased bleeding with trauma or a surgical procedure.

Three forms of the disease are distinguished based on vWF concentration and function. Dogs with Type I vWD (by far the most common) have mild to moderate bleeding abnormalities, depending on the level of vWF. The much rarer types II and III vWD cause severe bleeding disorders.

How is ... inherited?:

The most common form (Type I vWD) is inherited as an autosomal trait with incomplete dominance. This means offspring may inherit the disorder if either parent carries the gene, but not all offspring will be affected to the same extent. Dogs with type I disease have reduced but measurable levels of Von Willebrand factor (1 to 60 per cent) and mild to moderate bleeding tendencies. Animals that inherit the gene for type I vWD from both parents (homozygotes) die before birth or shortly thereafter. The gene for the condition is widespread in the Doberman pinscher population.

Dogs with Types II and III von Willebrand's disease have severe bleeding abnormalities. Both types are relatively rare. Inheritance is autosomal recessive, meaning animals are only affected if they inherit the abnormal gene from both parents, who are clinically unaffected carriers. Affected dogs have very low, poorly functioning (Type II) or non-existent (Type III) levels of vWF, while carrier parents have a reduction in normal levels.

What breeds are affected by ... ?:

What does ... mean to your dog & you?:

Although many dogs are affected by vWD, only a small proportion have severe problems. Dogs with vWD are prone to nose bleeds, bleeding from the gums, and prolonged bleeding during heat or after whelping. There may be prolonged bleeding from the umbilical cord at birth or when your pup sheds its baby teeth. Excessive bleeding after surgery or trauma is common, and may be the first sign of this condition in your dog. You may see blood in your dog's urine or stool.

Most dogs with vWD can lead normal lives, with occasional bleeding episodes that may go unnoticed or can be treated appropriately. Other illnesses, or physical or emotional stress, may worsen bleeding episodes. In affected dogs, it is best to consult your veterinarian before using any over-the-counter medications. Drugs such as aspirin, for example, alter the function of platelets and should be avoided in dogs with bleeding disorders.

How is ... diagnosed?:

Because the severity of bleeding with von Willebrand's disease is quite variable, often the disease is not diagnosed until the dog is 3 to 5 years old. Your veterinarian may suspect vWD because of a history of abnormal bleeding in your dog, such as unexplained nosebleeds, or there may be heavy bleeding during surgery. Stillbirths or pups that die shortly after birth ("fading puppies") may be a result of both parents being carriers of the gene for von Willebrand's disease. There are specialized tests available to make the diagnosis of von Willebrand's disease. One is a genetic test and the other measures blood levels of von Willebrand factor.

FOR THE VETERINARIAN
Mucosal bleeding time is the best screening test for a potential defect in platelet function, and is prolonged in dogs with a deficiency in vWF. However the test is non-specific for vWD because it is also prolonged in dogs with thrombocytopenia or functional platelet defects. Specific diagnosis of vWD requires either genetic testing in those breeds in which it is available, or vWF measurement. The genetic test is performed by submitting a sample (such as a mucosal scraping) to a genetic testing laboratory (e.g., vetGen). The results are reliable at any age. Measurement of vWF:Ag levels is done by electroimmunoassay or enzyme-linked immunoabsorbent assay (ELISA). A vWF:Ag ratio of less than 50% is evidence of vWF deficiency, but clinical bleeding tendencies are usually only apparent with a more severe deficiency (<25%). The methods used to draw, process, and ship samples are very important for accurate results. It is best to check with your diagnostic laboratory for shipping instructions. VWF levels vary between breeds and with respect to age.

Because of the possible link with hypothyroidism, thyroid status should be evaluated.

How is ... treated?:

This condition cannot be cured but it can be managed. Your veterinarian will discuss this with you when the diagnosis is made. You will likely be able to control mild bleeding yourself by applying prolonged pressure. In other circumstances, veterinary care such as cautery or sutures may be required. Severe bleeding episodes are treated by administering a source of von Willebrand factor through a transfusion. If your dog requires surgery, your veterinarian may recommend a transfusion pre-operatively as a precaution, depending on the severity of the bleeding disorder, and the type of surgery. Thyroid supplements may help to control bleeding, if your veterinarian determines that your dog is hypothyroid.

FOR THE VETERINARIAN
Exogenous vWF may be supplied through administration of fresh whole blood, fresh or fresh-frozen plasma, or cryoprecipitate (treatment of choice to provide high concentraions of vWF and avoid volume overload). Dogs with severe vWD should be blood-typed because repeated transfusions may be required. Where possible, avoid the use of drugs that have been known to cause thrombocytopenia or otherwise affect platelets. Such drugs include NSAIDs, sulfonamide antibiotics, cytotoxic drugs, antihistamines, phenothiazines, theophylline,heparin and coumadin, and estrogen. Some studies have shown that thyroid supplementation in euthyroid dogs can reduce bleeding, but other studies have contradicted this.

Breeding advice:

The trait for von Willebrand's disease is widespread, particularly in Doberman pinschers, but also in several other breeds. An accurate genetic test has been developed for several breeds - testing can reliably identify dogs with vWD, dogs that are carriers, or dogs that are clear (see vetGen for information on testing and the breeds in which it is available). In breeds where specific genetic tests are not yet available, carriers of the trait can still be identified through the blood test for von Willebrand factor. These dogs have reduced levels of vWF (25 to 60 per cent) but do not have bleeding problems. Levels vary with age and between breeds. Where a bleeding disorder has been identified, breeders are advised to test breeding stock. Dogs with von Willebrand's disease and those who are carriers should not be used for breeding.

Resources:

Brooks MB. von Willebrand Disease. In: Côté E, ed. Clinical Veterinary Advisor Dogs and Cats. Missouri: Mosby Elsevier, 2007:1160-1162.
Brooks MB.Emergency management of canine von Willebrand's disease. 1996.A.C.V.I.M. Proceedings of the 14th Annual Vet. Medical Forum.34.
Sargan DR. von Willebrand's disease. In IDID - Inherited diseases in dogs:web-based information for canine inherited disease genetics.
vetGen - information on genetic testing available

Platelet dysfunction (thrombocytopathia, Basset hound thrombopathia)

roblib — Fri, 06 May 2011 17:06:41 +0000

What is ... ?:

These are disorders of small blood cells called platelets or thrombocytes. Platelets play an important role at several stages of the body's response to any injury that causes bleeding. One function of platelets is to aggregate or "clump" at the site of blood vessel injury to form an initial plug. Platelets also facilitate blood clotting, in conjunction with the clotting factors, and release substances active in inflammation and tissue repair. With these disorders, platelets do not respond normally to the activation signals that occur following injury to a blood vessel. Affected dogs are therefore more susceptible to bruising and hemorrhage.

Disorder	Abnormality	Breeds affected	Special tests
Basset thrombopathia (disorder of signal transduction)	Platelets fail to aggregate and secrete granules in response to normal stimuli	Basset hound, Finnish spitz	abnormal platelet adhesion and aggregation, normal clot retraction
Thrombasthenia	membrane glycoprotein disorder; reduction or absence of membrane proteins necessary for normal platelet function	Otterhound, Great Pyrenees	abnormal adhesion and clot retraction, aggregation failure, reduced or absent GPIIb/IIIa
Storage pool defect	defect in secretory granules	American cocker spaniel	abnormal aggregation, normal clot retraction, abnormal ADP secretion and storage
Platelet procoagulant deficiency		German shepherd	normal aggregation and secretion, normal clot retraction, abnormal prothrombinase activity
Complex or undefined		Collie, boxer	abnormal platelet function

How is ... inherited?:

These traits are autosomal, with recessive or unknown expression.

What breeds are affected by ... ?:

What does ... mean to your dog & you?:

Some dogs have only a mild bleeding tendency which is fairly easily controlled. With dogs who are prone to more severe bleeding, owners will need to be particularly attentive to catch small injuries and attend to them, and seek veterinary attention if necessary.

In affected dogs, it is best to consult your veterinarian before using any over-the-counter medications. For example, drugs such as aspirin alter the function of platelets, and should be avoided in dogs with bleeding disorders.

How is ... diagnosed?:

Generally these dogs are brought to the veterinarian at a young age when the owner notices unusual bleeding. This can be in the form of nose bleeds, blood in the urine or stool, or small hemorrhages or bruising in the skin, ears, mouth or retina of the eye. There may also be prolonged bleeding in response to a small injury. Where the bleeding tendency is mild, the condition may only be suspected when your dog first undergoes surgery.

Your veterinarian will do blood tests to determine the cause of the abnormal bleeding. With this condition, platelet numbers are normal but those tests that measure platelet function will have abnormal results.

For the veterinarian: Mucosal bleeding time is prolonged. Platelet numbers and blood coagulation parameters are generally normal. Platelet function testing for classification of hereditary defects may require referral (clot retraction, platelet aggregation and secretion studies, flow cytometry). Platelet dysfunction should be considered in any young dog with abnormal bleeding when more common disorders (von Willebrand's, thrombocytopenia, coagulopathies) have been ruled out.

How is ... treated?:

This condition cannot be cured but it can be managed, depending on the severity. Your veterinarian will discuss this with you when the diagnosis is made. You may be able to control mild bleeding by applying prolonged pressure. In other circumstances, sutures may be required. Severe bleeding will require transfusion of fresh platelets, either in the form of fresh whole blood or platelet-rich plasma. If your dog requires surgery, your veterinarian may recommend a transfusion pre-operatively as a precaution, depending on the severity of your dog's thrombopathia and the type of surgery.

Breeding advice:

Affected dogs, their parents (who are carriers), and their siblings (approximateley 50% of whom will be carriers) should not be used for breeding.The trait for thrombasthenic thrombopathia has been largely eliminated from the otterhound population through selective breeding.

Resources:

Brooks MB, Catalfamo JL. Platelet dysfunction. In: Bonagura JD, Twedt DC, eds. Kirk's Current Veterinary Therapy XIV. Missouri: Saunders Elsevier, 2009:292-297.
Brooks MB. Platelet dysfunction. In: Côté E, ed. Clinical Veterinary Advisor Dogs and Cats. Missouri: Mosby Elsevier, 2007:66-68.