| Comparative Coagulation |
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Clinical Topics - Hemophilia A
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| Hemophilia A is the most common severe inherited coagulation disorder
in animals and human beings. In dogs, as in other species, the disease
arises as the result of spontaneous mutation. Once hemophilia appears
in a family, the defect can then be transmitted through many generations.
This article provides an overview of hemophilia, including information
on inheritance pattern, clinical signs, and methods of identifying
hemophilia affected and carrier dogs. |
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Cause |
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| The bleeding tendency of Hemophilia A is caused by
specific deficiency of a single clotting factor, Factor VIII. The
clotting factors are designated by roman numeral and Factor VIII (factor
eight) is critical for normal blood clot formation. Abnormalities,
or mutations, in the Factor VIII gene prevent the body's production
of a normal, functional coagulation Factor VIII. |
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Inheritance |
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| The gene for Factor VIII is carried on the X chromosome
and the presence of one normal gene is sufficient to prevent hemophilia.
This form of inheritance is called sex-linked (or X-linked), recessive.
All males have one gene for Factor VIII which they inherit from their
dam. All females have two genes for Factor VIII, one inherited from
dam and one from sire. |
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Expression and Transmission |
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Males having one normal gene and females having two normal genes for
Factor VIII are clear of the hemophilia A trait and will not transmit
this defect to offspring. |
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Males having one abnormal gene are affected with hemophilia and will
transmit that abnormal gene to all their daughters, but to none of
their sons. |
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Females having one normal and one abnormal gene are asymptomatic carriers
and will transmit the abnormal gene, on average, to one half of their
sons and one half of their daughters. |
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If an X chromosome carrying a normal gene for Factor VIII is represented
as XH, and an X carrying the abnormal or hemophilic gene is represented
as Xh then the different possibilities for clinical status (phenotype)
and genetic makeup (genotype) can be represented as follows: |
| Phenotype |
Genotype |
| Normal male |
XHY |
| Normal female |
XHXH |
| Affected male |
XhY |
| Carrier female |
XhXH |
| Affected female |
XhXh |
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| Hemophilia is most commonly propagated within a line
when asymptomatic carrier females are bred to normal males. The male
puppies produced from this mating with each have a 50:50 chance of
being affected with hemophilia, and the females will each have a 50:50
chance of being a carrier. On average, the following 4 categories
of offspring types will occur in equal numbers. |
| Parental type |
Offspring types |
| Carrier female and normal male |
normal male |
XHY |
| (XhXH and XHY) |
affected male |
XhY |
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normal female |
XHXH |
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carrier female |
XhXH |
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Clinical Signs |
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| Hemophiliacs may bleed spontaneously into joints or
muscles resulting in lameness and swelling. Severe, often fatal hemorrhage
can occur into the chest or abdominal cavity. Bleeding under the skin
results in soft swellings called hematoma. If a hemophiliac undergoes
trauma or surgery then excessive hemorrhage occurs at the injured
site. Different mutations responsible for hemophilia cause variable
severity of bleeding tendency. Some forms of hemophilia are so severe
that most affected dogs will die within the first few weeks of life.
Other forms may be less severe, where affected dogs will survive,
but exhibit intermittent signs of bleeding. |
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Laboratory diagnosis |
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Coagulation assays performed on a specially prepared
blood sample are needed to diagnose hemophilia in dogs. The APTT (activated
partial thromboplastin time) is a screening test for coagulation defects,
and this test is abnormal in hemophiliacs. A specific diagnosis of
hemophilia A must be based on specific measurement of canine coagulation
Factor VIII - hemophilic dogs have a marked reduction in Factor VIII
activity compared to normal dogs.
In properly prepared samples, using tests validated for dogs, the
laboratory diagnosis of hemophilia affected dogs is highly accurate.
Unfortunately, coagulation assays may not always distinguish between
carrier and clear females. In general, carrier females have low levels
of Factor VIII, but there is some overlap between carrier and clear
females at the low end of Factor VIII's normal range. The accuracy
of carrier detection can be enhanced by measuring another blood protein
related to Factor VIII (von Willebrand factor) and then determining
a ratio of these two proteins. It is still possible, however, for
some carrier females to be misclassified. Pedigree analysis, in combination
with laboratory assay, is therefore very important. |
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Pedigree analysis and breeding recommendations |
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| Evaluation of pedigrees can determine carrier status
of some asymptomatic females, allow estimates of risk for carrier
status, and help to confirm laboratory diagnosis of affected males
or females. All daughters and dams of hemophilic males are obligate
carriers of hemophilia and should not be used for breeding. These
females can be safely spayed, and are clinically normal. The full
sisters and maternal half sisters of hemophilic males have a 50% chance
of being carriers of hemophilia. The best policy is not to breed these
females. Males can be confirmed clear of hemophilia by laboratory
testing, and all sons of obligate or possible carrier females should
be screened for hemophilia. Males that are confirmed test clear can
safely be used for breeding without further propagation of the defect. |
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Additional information-Screening for Hemophilia A in purebred dogs |
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| The Comparative Coagulation Section, at Cornell University's
Diagnostic Laboratory provides assays for identification of canine
hemophilia A, and more specialized tests for carrier detection in
females. The test program is confidential, results are released only
to the submittor. For the most complete and accurate evaluation, we
encourage submission of pedigrees with all samples, and progeny testing
(evaluation of offspring and parents) in affected lines. Because sample
quality is critical for valid test results, we provide detailed instructions
and supplies for drawing and processing canine blood samples. Please
feel free to contact our laboratory for more information. |
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Canine Hemophilia A Study
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