Bleeding Disorders in Animals - WSAVA2005 - VIN 7/29/23, 12:23 PM

Bleeding Disorders in Animals

WORLD SMALL ANIMAL VETERINARY ASSOCIATION WORLD CONGRESS PROCEEDINGS, 2005

W. Jean Dodds, DVM
Hemopet
Garden Grove, CA, USA

Hereditary Disorders
Fibrinogen (Factor I) Deficiencies
Hereditary fibrinogen deficiencies have been recognized in Saanen dairy goats
in the Netherlands and several dog breeds (St. Bernards in West Germany;
borzoi, vizsla and collie families in North America). These disorders can be
caused by a complete lack of fibrinogen (afibrinogenemia), reduced fibrinogen
(hypofibrinogenemia), or an abnormal fibrinogen (dysfibrinogenemia). These
defects produce a mild to severe or fatal bleeding diathesis and have an
autosomal inheritance pattern.
Prothrombin (Factor II) Deficiency
Prothrombin defects are caused by both hypo- and dys-prothrominemia. These
are autosomal disorders that produce mild to moderately severe bleeding
problems. The only inherited prothrombin abnormality recognized to date in
animals occurred in a family of boxer dogs from Texas. The defect was
characterized by epistaxis and umbilical bleeding in newborn puppies and mild
mucosal surface bleeding in young adults. Prothrombin deficiency has also been
reported in an English cocker spaniel.
Vitamin K-Dependent Coagulation Factor Deficiency
Combined deficiency of all vitamin K-dependent coagulation factor (II, VII, IX and
X) has been reported in a family of Devon Rex cats. The feline disorder was
vitamin K responsive and was inherited as an autosomal trait.
Factor VII Deficiency
Factor VII deficiency is commonly reported worldwide in beagle dogs from large
commercial breeding colonies. The apparent high incidence in this breed
probably reflects the widespread use of beagles in biomedical research. It has
also been described in an Alaskan malamute, bulldogs, and mixed breeds. The
disorder is usually discovered fortuitously during routine hematological screening
for drug testing, research, or clinical workup. Canine factor VII deficiency is
typically a mild disease with no overt bleeding tendency except for easy bruising.
Hemophilia A (Factor VIII: C Deficiency, Classic Hemophilia)

https://www.vin.com/apputil/content/defaultadv1.aspx?id=3854231&pid=11196&print=1 Page 1 of 7
Bleeding Disorders in Animals - WSAVA2005 - VIN 7/29/23, 12:23 PM

The most common of the severe inherited coagulopathies, hemophilia A occurs

in humans, dogs, horses, sheep, cattle and cats. Mild, moderate, and severe
forms of hemophilia have been recognized in humans and dogs, whereas the
equine defect is usually severe and the feline defect tends to be mild. The
canine disease has been reported in nearly every pure breed of dogs and in
mongrels, but is most common in German shepherds worldwide having
descended from the obligatory carrier progeny of an influential hemophilic stud.
Smaller breeds tend to be less severely affected than larger breeds.
Thoroughbred, Standardbred, and Quarter horses have been reported with
hemophilia, as have several breeds and mixed breeds of cats, Australian
Hereford cattle and Dutch sheep.
Hemophilia is an X chromosome-linked recessive trait in humans and other
animals. Affected males are hemizygous for the trait, whereas carrier females are
heterozygous and affected females (the product of a hemizygous and
heterozygous mating) are homozygotes. This disease results in males from a
very low concentration of clotting factor VIII:C, whereas carrier females have
amounts of factor VIII:C of about 40-60% of normal.
Hemophilia B (Factor IX Deficiency, Christmas Disease)
Hemophilia B, also an X chromosome-linked recessive trait, is less common
than hemophilia A and occurs in humans, about 20 breeds of dogs, and several
breeds of cats as well as mixed breeds. It occurs as a mild to moderate disorder
of small dog breeds (e.g., Cairn terrier, American cocker spaniel, Shetland
sheepdog, Scottish terrier, and French bulldog) and cats, and as a severe
diathesis in larger breeds (e.g., black and tan coonhounds, St. Bernards,
Alaskan malamutes, Old English sheepdogs, and German shepherds).
As in classic hemophilia, carrier females can be identified by reduced (40-60%)
levels of factor IX., although affected males have all had less than 5% factor IX. It
is important to perform accurate diagnostic tests to differentiate between the
hemophilias as both disorders have markedly prolonged intrinsic system clotting
tests. The plasma defect of hemophilia B is corrected by addition of fresh normal
serum, whereas that of hemophilia A is not because serum contains factor IX but
not FVIII:C activity.
von Willebrand's Disease (vWD)
von Willebrand first described the complex, multifaceted syndrome known as
vWD in humans in 1926. The disorder is usually more mild than the hemophilias,
and primarily involves mucous membranes and skin, with gastrointestinal and
urogenital bleeding and epistaxis as common symptoms. The prolonged
bleeding time also results in excessive surgically induced hemorrhage. The most
common inherited bleeding disorder of humans, vWD has been recognized in
swine, more than 60 dog breeds, several breeds of cats, a quarter horse family,
and an inbred strain of laboratory rabbits. The affected breeds with a high
prevalence of the gene are Doberman pinscher (80% prevalence), German
shepherd, miniature schnauzer, golden retriever, Shetland sheepdog, basset
hound, standard poodle, keeshond, rottweiler, dachshund, Scottish terrier,

https://www.vin.com/apputil/content/defaultadv1.aspx?id=3854231&pid=11196&print=1 Page 2 of 7
Bleeding Disorders in Animals - WSAVA2005 - VIN 7/29/23, 12:23 PM

Manchester terrier, and Pembroke Welsh corgi. In other breeds, the disorder is
either less prevalent or the true prevalence is unknown because too few animals
have been studied.
By far the most common form of canine vWD is type 1, inherited as an
autosomal, incompletely dominant trait with variable clinical and laboratory
expression based on the degree of penetrance of the mutant gene. In four dog
breeds, Scottish terriers, Chesapeake Bay retrievers, Shetland sheepdogs, and
German wirehaired pointers, in Himalayan cats, and Poland-China swine, vWD is
analogous to the autosomal recessive type 3 vWD of humans. Homozygous
affected animals make no measurable von Willebrand factor (vWF) and exhibit a
moderate to severe bleeding tendency, whereas heterozygotes are detected by
laboratory tests only (reduced vWF antigen or activity) and are otherwise
asymptomatic.
In addition to the more commonly recognized types 1 and 3 vWD, many
variants exist and are classified as type 2 vWD. Examples include families of
German shorthair pointer dogs, and Quarter horses. The nationwide genetic
screening program for canine vWD begun by the author in 1980, has since tested
about 30,000 Doberman pinschers, 12,000 Shetland sheepdogs, 9,000 golden
retrievers, 8,000 Scottish terriers, 5,000 Pembroke Welsh corgis, 5,000 standard
and miniature poodles, and several thousand miniature schnauzers, basset
hounds, Akitas.
In dogs, vWD is exacerbated by concurrent hypothyroidism, so that
asymptomatic carriers may exhibit a bleeding tendency if they develop
autoimmune thyroiditis and become hypothyroid, a common situation found in
many breeds, but especially prevalent in Doberman pinschers. Furthermore,
hypothyroid dogs may exhibit thrombocytopenia and associated mucosal surface
bleeding. Clinical experience with use of thyroid supplement, which
nonspecifically shortens the bleeding time in animals with inherited or acquired
vWD and other platelet dysfunctions, has supported the efficacy, safety and low
cost of this approach.
Thyroid supplementation alone may suffice to control bleeding in mild to
moderate vWD, a situation analogous to the use of desmopressin (DDAVP) or
danazol to control bleeding in humans and animals. Because of the important
role of vWF in sustaining platelet adhesion, animals that are asymptomatic
heterozygotes for vWD (as determined by reduced vWF:Ag), are at risk to
express a bleeding tendency if some other hemostatic disorder develops (e.g.,
rodenticide toxicosis, thrombocytopenia, liver disease, hypothyroidism).
Factor X Deficiency
A rare coagulation disorder, canine factor X deficiency was first described in the
early 1970s in a family of American cocker spaniels. Since then, factor X
deficiency has been diagnosed occasionally in mongrel dogs and more recently
in the Jack Russell terrier. Homozygotes and some heterozygotes have very low
levels of factor X (<6% to 35%) and a clinically expressed bleeding disease,
whereas most heterozygotes (40-70% factor X) are asymptomatic. Affected dogs

https://www.vin.com/apputil/content/defaultadv1.aspx?id=3854231&pid=11196&print=1 Page 3 of 7
Bleeding Disorders in Animals - WSAVA2005 - VIN 7/29/23, 12:23 PM

with less than 20% factor X usually do not survive neonatal life. The exception
was an affected mongrel puppy with 6% factor X that lived for nearly a year
before experiencing a fatal bleeding episode. This disease mimics the "fading
puppy syndrome," as severely affected pups are stillborn or fade and die in the
first week or two of life. Necropsies show massive internal bleeding. Signs in
adults are mild and referable to mucosal surfaces. Complete absence of factor X
is thought to be a lethal mutation because of its central role in coagulation.
Factor XI (PTA) Deficiency
Factor XI deficiency is a rare disorder of humans, most of whom are of Jewish
background. Clinical signs are mild (hematuria, bruising, epistaxis, menorrhagia)
unless the patient is subjected to surgical procedures. Bleeding usually starts
12-24 hrs after surgery and can be severe and protracted. Lethal bleeding has
also been reported after minor procedures such as biopsies and tonsillectomy.
The disorder also occurs in Holstein cattle, English springer spaniels, great
Pyrenees, and Kerry blue terrier dogs, and is clinically similar to that of humans.
Factor XII Deficiency (Hageman Trait)
Hageman trait is an asymptomatic coagulation deficiency recognized in humans,
dogs, and quite commonly in cats. The first feline case was discovered
fortuitously by prolonged screening tests of intrinsic clotting. It had less than 5%
factor XII and died without progeny. The second case, also discovered by
screening tests, had less than 1% factor XII and has provided several
generations of progeny.
In addition to these defects, the absence of detectable biological or
immunological factor XII is a normal phenomenon of a variety of other vertebrates
and invertebrates, such as whales, birds (including the common domestic fowl
and waterfowl), reptiles, and possibly fish.
Platelet Function Defects
1. Thrombasthenia (Glanzmann's Disease). This bleeding disease has an
autosomal inheritance, and is characterized by major reduction in clot
retraction, occasional mild thrombocytopenia, but normal platelet
morphology. The bleeding diathesis is severe and of the purpuric type, and
epistaxis is common and profuse. The first animal cases were discovered
in 1967 in a family of otterhound dogs. Both homozygotes and
heterozygotes could be identified by abnormalities in specific platelet
function tests. Bleeding episodes can be triggered by stress events.
2. Thrombopathia. A group of inherited thrombopathias have been
described in humans, fawn-hooded rats, basset hounds, spitz dogs,
American cocker spaniels, Simmental cattle, and cats. The defect in fawn-
hooded rats and American cocker spaniels is similar to that of human
platelet storage-pool disease. Canine thrombopathia (CTP) is an
autosomally inherited bleeding disorder of the basset hound and spitz
dogs. These conditions produce a bleeding tendency primarily of mucosal
surfaces and intrinsic to the platelet.

https://www.vin.com/apputil/content/defaultadv1.aspx?id=3854231&pid=11196&print=1 Page 4 of 7
Bleeding Disorders in Animals - WSAVA2005 - VIN 7/29/23, 12:23 PM

Other Defects
1. Complement Deficiencies. A variety of inherited complement deficiencies
are recognized in humans, whereas only three known similar disorders
have been seen in other species. These are C4 deficiency in guinea pigs
and rats, C5 deficiency in mice, and C6 deficiency in hamsters and rabbits.
2. Double Hemophilia (Hemophilia AB). A planned cross-breeding study
between dogs with hemophilia A and hemophilia B was undertaken to
study possible linkage between these two X chromosome genes. Dogs
with double hemophilia were readily produced, thus demonstrating that the
loci for hemophilia A and B are located far apart on the X chromosome.
3. Prekallikrein Deficiency (Fletcher Trait). Prekallikrein activity has been
recognized in apes, swine, guinea pigs, mice, goats, sheep, and horses
but is absent or minimal in dogs, cats, cattle, rabbits, whales, ducks, and
chickens. Fletcher trait has recently been described in dogs, and miniature
and Belgian horses.
Acquired Disorders
Acquired bleeding disorders are numerous and more common than the inherited
deficiencies of clotting factors and platelets.
Platelet Function Defects
1. Quantitative (Thrombocytopenias and Thrombocytosis). The majority
of chronic cases of thrombocytopenia are immune-mediated. Primary
immunological thrombocytopenia, of unknown etiology, has been termed
idiopathic thrombocytopenic purpura. The majority of cases, however,
appear secondary to a variety of underlying conditions such as use of
heparin or estrogens, thrombosis, neoplasia, viral diseases, vaccine-
associated reactions, other drugs and chemicals. Non-immunological
thrombocytopenias are less common and have a better prognosis than the
immunological cases, if the causative agent for disease can be eliminated.
2. Qualitative. A group of diseases and a large number of drugs are known
to produce thrombopathias. Most drugs act by inhibiting the adhesion of
platelets to subendothelium (aspirin, which blocks platelet cyclic
endoperoxides) and/or the platelet release reaction (phenylbutazone,
sulfonamides, antiinflammatory drugs, ticlopidine, promazine tranquilizers).
Drugs that interfere with platelet function are contraindicated or must be
used with caution in animals moderately or severely affected with bleeding
disorders. Similarly, elective surgery should be avoided during the viremic
phase (3-10 days) after live virus vaccination or viral exposure.
The most common diseases causing platelet dysfunction are renal failure,
uremia and liver disease. Less common causes are the dysproteinemias such as
myelomas and macroglobulinemias and estrogen toxicity. The classic clinical
case of uremic bleeding is that of the old dog with compensated chronic

https://www.vin.com/apputil/content/defaultadv1.aspx?id=3854231&pid=11196&print=1 Page 5 of 7
Bleeding Disorders in Animals - WSAVA2005 - VIN 7/29/23, 12:23 PM

interstitial nephritis which has inflamed gums and chronic periodontal disease.
Dentistry on such a patient frequently results in excessive and prolonged gingival
bleeding.
Disseminated Intravascular Coagulation with Fibrinolysis
The combined syndrome of DIC and secondary fibrinolysis is an important acute,
subacute, or chronic disease process of humans and other animals. The major
causes include viral, bacterial, protozoal, and parasitic infections; neoplasia;
obstetric complications; and miscellaneous conditions such as trauma, shock,
laminitis, heat stroke, colic, burns, drowning, liver disease, and canine
heartworm disease.
Liver Disease
As the liver is the primary site of clotting factor synthesis, acute or chronic
generalized hepatic disease often results in a bleeding tendency.
Vitamin K Deficiency and Rodenticide Toxicity
The vitamin K-dependent clotting factors (II, VII, IX, X) are reduced in rodenticide
toxicity (accidentally ingested or from therapeutic overdosage), in malabsorption
syndromes, and in sterilization of the gut by prolonged use of antibiotics.
Diagnosis is confirmed laboratory clotting tests, and a corrective response to
treatment with whole blood or plasma transfusion and/or treatment with vitamin
K1 . The newer second-generation rodenticides are 20-50 times more potent and
longer lasting (several weeks) than first-generation warfarin compounds.
References
1. Brooks M, Dodds WJ, Raymond,SL. Epidemiologic features of von Willebrand's disease in
Doberman Pinchers, Scottish Terriers, and Shetland Sheepdogs: 260 cases (1984-1988). J Am
Vet Med Assoc 200:1123-1127, 1992.
2. Brooks MB, Raymond SL, Catalfamo JL. A severe recessive form of von Willebrand's disease in
German Wirehaired Pointers. J Am Vet Med Assoc 209: 926-929, 1996.
3. Brooks MB, Raymond SL, Catalfamo JL. Plasma von Willebrand factor antigen concentration
as a predictor of von Willebrand's disease status in German Wirehaired Pointers. J Am Vet
Med Assoc 209: 930-933, 1996.
4. Brooks MB, Erb HN, Foureman PA, Ray K. von Willebrand disease phenotype and von
Willebrand marker genotype in Doberman Pinchers. Am J Vet Res 62: 364-369, 2001.
5. Catalfamo JL, Dodds WJ. Hereditary and acquired thrombopathias. Hemostasis 18, 185-193,
1988.
6. Cook AK, Werner LL, O'Neill SL, Brooks M, Feldman BF. Factor X deficiency in a Jack Russell
terrier. Vet Clin Pathol 22, 68-71. 1993.
7. Dodds WJ. Bleeding disorders. In "Consultations in Feline Internal Medicine (JR August, ed.),
1991, pp. 383-388. W.B. Saunders, Philadelphia, Pennsylvania.

8. Dodds WJ. Bleeding disorders. In "Handbook of Small Animal Practice" (RV Morgan, ed.), 2nd
Ed., 1992, pp. 765-777. Churchill Livingstone, New York, New York.
9. Dodds WJ, Raymond SL,Brooks MB. Inherited and acquired von Willebrand's disease. Parts 1
and 2. Vet Pract STAFF 5(4 and 5), 14-17 and 21-23. 1993.
10. Dodds WJ. Hypothyroidism and von Willebrand factor. J Am Vet Med Assoc 206, 594-595,
1995.

https://www.vin.com/apputil/content/defaultadv1.aspx?id=3854231&pid=11196&print=1 Page 6 of 7
Bleeding Disorders in Animals - WSAVA2005 - VIN 7/29/23, 12:23 PM

11. Dodds WJ. Estimating disease prevalence by health surveys and genetic screening. Adv Vet
Sci Comp Med 39, 29-96, 1995.

12. Dodds WJ. Hemostasis. In "Clinical Biochemistry of Domestic Animals" (JJ Kaneko, D Bruss,
eds.), 5th Ed, 1997, pp. 241-283. Academic Press, San Diego,
13. Feldman DG, Brooks MB, Dodds WJ. Hemophilia B (factor IX deficiency) in a family of German
shepherd dogs. J Am Vet Med Assoc 206, 1901-1905, 1995.
14. Gentry PA, Ross ML. Coagulation factor XI deficiency in Holstein cattle: expression and
distribution of factor XI activity. Can J Vet Res 57, 242-247, 1993.

15. Geor RJ, Jackson ML, Lewis KM, Fretz PB. Prekallikrein deficiency in a family of Belgian
horses. J Am Vet Med Assoc 197, 741-745, 1990.

16. Giger U. The bleeding surgical patient: practical testing and management. Proc. 12th ACVIM
Forum, 1994, pp. 155-157.

17. Grindem CB, Breitschwerdt EB, Corbett WT, Jans HE. Epidemiologic survey of
thrombocytopenia in dogs: a report on 987 cases. Vet Clin Pathol 20, 38-43, 1991.
18. Joseph SA, Brooks MB, Coccari PJ, Riback SC. Hemophilia A in a German shorthaired pointer:
clinical presentations and diagnosis. J Am Anim Hosp Assoc 32, 25-28, 1996.
19. Knowler C, Giger U, Dodds WJ, Brooks M. Factor XI deficiency in Kerry Blue Terriers. J Am Vet
Med Assoc 205, 1557-1561, 1994.

20. Kristensen AT, Weiss DJ, Klausner JS. Platelet dysfunction associated with immune-mediated
thrombocytopenia in dogs. J Vet Int Med 8, 323-327, 1994.

21. Maddison JE, Watson ADJ, Eade IG, Exner T. Vitamin K-dependent multifactor coagulopathy in
Devon Rex cats. J Am Vet Med Assoc 197, 1495-1497, 1990.

22. Maggio-Price L, Dodds WJ. Factor IX deficiency (hemophilia B) in a family of British shorthair
cats. J Am Vet Med Assoc 203, 1702-1704, 1993.
23. Otto CM, Dodds WJ, Greene CE. Factor XII and partial prekallikrein deficiencies in a dog with
recurrent gastrointestinal hemorrhage. J Am Vet Med Assoc 198, 129-131, 1991.
24. Peterson JL, Couto CG, Wellman ML. Hemostatic disorders in cats: a retrospective study and
review of the literature. J Vet Int Med 9, 298-303, 1995.

25. Raymond SL, Jones DW, Brooks MB, Dodds WJ. Clinical and laboratory features of a severe
form of von Willebrand disease in Shetland sheepdogs. J Am Vet Med Assoc197, 1342-1346,
1990.
26. Riehl J, Okura M, Mignot E, Nishino S. Inheritance of von Willebrand's disease in a colony of
Doberman Pinchers. Am J Vet Res 61: 115-120, 2000.

27. Stokol T, Parry BW, Mansell PD, Richardson JL. Hematorrhachis associated with hemophilia A
in three German shepherds dogs. J Am Anim Hosp Assoc 30, 239-243, 1994.

28. Venta PJ, Li J, Yuzbasiyan-Gurkan V, Brewer GJ, Schall WD. Mutation causing von
Willebrand's disease in Scottish Terriers. J Vet Int Med 14: 10-19, 2000.

SPEAKER INFORMATION
(click the speaker's name to view other papers and abstracts submitted by this speaker)

W. Jean Dodds, DVM

Hemopet
Garden Grove, CA

URL: https://www.vin.com/doc/?id=3854231

https://www.vin.com/apputil/content/defaultadv1.aspx?id=3854231&pid=11196&print=1 Page 7 of 7