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2001 UPDATE ON HEREDITARY BLEEDING DISORDERSPART 1: VON WILLEBRAND DISEASE

By Marjory Brooks, DVM, Diplomate ACVIM

Comparative Coagulation Section, Cornell University


Von Willebrand Disease (abbreviated vWD) is caused by lack of a specific protein called von Willebrand factor. This protein circulates in the bloodstream and is required for control of bleeding from sites of blood vessel injury. German wirehaired pointers affected with vWD have very low levels of von Willebrand factor (in most cases about 1% of normal levels) and this protein has an abnormal structure, further compromising its function. This form of vWD is referred to as type 2 vWD. To date, type 2 vWD has only been identified in 2 breeds: German wirehaired pointers and German shorthaired pointers.


Clinical signs of vWD in German wirehaired pointers are relatively severe compared with vWD in other breeds, such as Doberman pinschers. Dewclaw removal, tattooing, and teething may cause excessive bleeding in vWD-affected pups. Other signs include prolonged bleeding from minor wounds, apparent spontaneous bleeding from the nose or mouth, and blood in urine or stool. Uncontrollable bleeding may occur after surgery. Although type 2 vWD is a severe form, it is not a “lethal” trait. Affected pups usually survive to adulthood, and with transfusion, can even undergo major surgery.


Treatment of a severe bleeding episode requires transfusion of canine blood products. No drug, vitamin, hormone, or dietary modification can replace von Willebrand factor. Bandages, sutures, and wound glue may control bleeding from minor injuries. VWD-affected dogs should not be given drugs that interfere with normal blood clotting. These drugs include aspirin, sulfa-type antibiotics, fish-oil supplements, and heparin.


Inheritance and expression pattern of vWD in German wirehaired pointers is autosomal recessive. All males and females have 2 vWF genes, 1 inherited from dam and 1 from sire. Only those dogs having 2 abnormal genes will express the bleeding tendency. Dogs having 1 abnormal and 1 normal gene are asymptomatic carriers. It must be stressed that vWD carriers are clinically normal and can undergo major surgery or trauma without excessive bleeding. Genetic and clinical status for vWD and predicted breeding outcomes can be simply diagrammed using the following symbols: V = normal vWF gene; Vm = mutant vWF gene


vWD-Clear (male or female), no signs of bleeding = VV

vWD-Carrier (male or female), no signs of bleeding = VVm

vWD-Affected (male or female), bleeding tendency = VmVm


Parental Types and Predicted Ratio of Offspring Types

Parental types Predicted ratio of offspring types

clear (VV) x clear (VV) all clear (VV)

clear (VV) x carrier (VVm) 1/2 clear (VV) & 1/2 carrier (VVm)

carrier (VVm) x carrier (VVm) 1/4 clear (VV) & 1/2 carrier (VVm) & 1/4 affected (VmVm)

Laboratory screening for vWD can be accomplished by measuring the amount of vWF protein in a blood sample. This vWF protein assay is called vWF antigen (abbreviated vWF:Ag), and the test result is a numeric value reported as the %vWF:Ag compared to a 100% standard. The methods used to draw, process, and ship samples are important for accurate results. Samples containing clots or hemolysis (red cell breakdown) are likely to yield inaccurate or irreproducible results.


Levels of vWF fluctuate slightly from day to day in normal, healthy dogs. This fluctuation is exaggerated during pregnancy or heat, and in any dog having a systemic illness. Baseline values of vWF:Ag are more accurate genetic predictors of vWD status, therefore samples for genetic screening should be drawn from healthy dogs and bitches not pregnant or in heat. Puppies can be sampled as young as 6 to 8 weeks of age.


Diagnostic ranges of vWF:Ag are used to identify vWD-affected dogs and as an aid for predicting genetic status for the vWD trait in asymptomatic dogs.


Diagnostic Ranges and Predicted Genetic Statuses

Diagnostic Range vWF:Ag Predicted Genetic Status

NORMAL 70 to 180% clear (VV)

BORDERLINE 50 to 69% inconclusive (VV or VVm)

ABNORMAL 50 to 69% carrier (VVm)

1 to 2% or lower affected (VmVm)

Dogs testing in the normal range are considered clear of the vWD trait, and at low risk for expressing or transmitting vWD.


Dogs testing in the borderline range fall in an overlap region of plasma vWF:Ag, where some are clear and some carriers of vWD. On a second test, some dogs fall in the normal or abnormal range, thereby enabling a prediction of their status. A test mating can be performed by breeding a borderline dog to a high-testing clear mate. If the borderline parent is clear of vWD, then all pups in the litter are predicted to be clear. The presence of 1 or more abnormal range pups indicates that the borderline parent is a carrier of vWD.


Dogs testing in the abnormal range are considered carriers of the vWD trait. They are at risk for transmitting an abnormal vWF gene to offspring, and those with very low values of vWF:Ag (1 to 2%) are affected with vWD.


Key Points:

The vWD trait can be transmitted and expressed by males and females

vWD-affected dogs are produced only when dam AND sire are carriers (or affected)

vWD carriers are clinically normal, but can be identified by a blood test

The ideal mating is between 2 vWD-clear parents, however a carrier bred to clear mate will produce (on average) 50% carrier and 50% clear offspring; there will be no affecteds.

Summary of vWD screening in Deutsch-Drahthaar


Type 2 vWD was first diagnosed in a German wirehaired pointer in 1989, although this form of vWD was previously known to be present in German shorthaired pointers. A small number of Deutsch Drahthaar (fewer than 20 dogs) were screened for vWD in 1989 and 1990, with widespread screening begun in 1991. Ultimately, in the peak test years of 1991 through 1996, more than 100 dogs were tested each year, representing more than 50 different kennels. Veterinarians and breeders submitted blood samples for vWF:Ag assay to the Comparative Coagulation Laboratory (located in Albany, NY until 1994 and since then in Ithaca, NY where the laboratory is affiliated with Cornell University’s Veterinary Diagnostic Laboratory). Dogs were classified on the basis of their vWF:Ag levels and clinical history into one of four diagnostic ranges as follows:


Diagnostic Ranges for Deutsch-Drahthaar for Type 2 vWD, 1996 study

Range Percentage of all dogs tested

Normal (vWF:Ag 70 to 180%) 81%

Borderline (vWF:Ag 50 to 69%) 6%

Carrier range (vWF:Ag 2 to 49%) 12%

Affected (vWF:Ag 1% or lower) 1%


Data from progeny tests (tests of entire litter, with dam and sire) during this period were also compiled for quantitative genetic analyses. Plasma vWF:Ag was found to be highly heritable, and the cutoff value of 70% appropriate for distinguishing between carrier and clear dogs. Use of this cutoff will minimize the risk of misclassifying a carrier as clear (predicted test accuracy of 95%). Selection based on parental vWF:Ag produced the predicted vWF:Ag values in offspring. Specifically, matings between 2 normal range parents produced almost exclusively normal range pups (98% normal range, 2% borderline range) and matings between 1 carrier and 1 normal range parent produced approximately 50 to 60% normal range pups, and the remainder carrier or borderline range (and NO affected pups).

These analyses of vWD and vWD screening in German wirehaired pointers have been published in peer-reviewed veterinary journals: Journal of the American Veterinary Medical Association, 1996 volume 209, p. 926-33 and The Veterinary Quarterly, 2001, volume 23, p. 126-128.


vWD Screening 1997 through 9/01


Samples from 353 German wirehaired pointers have been submitted to the Comparative Coagulation Laboratory for vWD screening (303 identified as Deutsch Drahthaar, 50 identified as German wirehaired pointers). The Drahthaar samples included 153 pups, representing 19 litters. The proportion of the 353 dogs testing in each diagnostic range follows:


Diagnostic Ranges for Deutsch-Drahthaar for Type 2 vWD, 2001 study

Range Percentage of dogs tested

Normal (vWF:Ag 70 to 180%) 77.3%

Borderline (vWF:Ag 50 to 69%) 15.5%

Carrier range (vWF:Ag 2 to 49%) 7.0%

Affected (vWF:Ag 1% or lower) 0.2%


Note: The dogs tested were not chosen randomly, therefore results cannot be assumed to reflect an overall breed frequency of the vWD trait. A single affected dog (submitted as a German wirehaired pointer) was identified in this time period.


Considerations for Screening Programs


The goal of a test program should be reduction in the frequency of unwanted traits, while preserving desirable traits and maintaining genetic diversity within the breed. High stringency selection, with immediate elimination of all vWD carriers from breeding programs, may not be in the best interest of the breed overall. Ignoring vWD, however, will result in increased prevalence of the trait and production of affected pups. The vWD trait is present in dogs bred in the United States and Europe, and was likely propagated in the breed through ancestors common to German wirehaired pointers and German shorthaired pointers. Care must be taken to ensure that the outcome of screening for genetic disorders is not discrimination against those kennels or lines that participate.


Screening strategies to reduce the prevalence of vWD


Results of vWF:Ag can be used as selection guidelines to rapidly or gradually reduce the vWD trait from a line, while ensuring that no affected pups are produced. Dogs having vWF:Ag in the normal range (> 70%) are predicted to be clear of vWD. If both parents are vWD clear, all pups will be vWD clear. Many Drahthaar classified as clear on the basis of individual test results are also progeny test clear (having produced entire clear litters when bred to clear mates). These proven dogs are ideal for breeding to untested or carrier mates. As long as 1 parent is vWD clear, there will be no affected pups in a litter. By identifying clear pups from these crosses, and reducing the number of carriers used for subsequent breeding, the number of vWD carriers produced can be reduced and ultimately eliminated from any line.


A “DNA test” to screen for vWD in German wirehaired pointers has been developed at the University of Utrecht in the Netherlands. Unfortunately, information on the test method and its validation have not been published. The test results are reported as noncarrier (vWD clear), heterozygote (carrier of vWD) or homozygote (vWD affected). Until more information is available on this test, it may be useful in some cases to measure vWF:Ag in individuals or progeny when planning subsequent matings. The commercial DNA tests for vWD offered by VetGen and Genesearch in the United States are NOT valid to screen for vWD in German Wirehaired pointers.


In summary, all dogs that express a bleeding tendency should be tested to establish a definitive diagnosis. If vWD is the cause of bleeding, then the parents of that individual are obligate carriers of vWD and screening close relatives to identify carriers before they are bred is warranted. Males and females (including untested imports) to be used in linebreeding or inbreeding programs should be tested to ensure they do not transmit vWD. Testing is less important, and may not be indicated, for offspring or mates of proven clear individual dogs, and for most clinically healthy dogs that are not bred. Group members should feel free to call the Coagulation Laboratory (607-275-0622) for any questions on von Willebrand disease.


This article appeared in the Verein Deutsch Drahthaar Group North America Newsletter, March 2002.


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