ellenm

I don't mean to ignore vwd status, by any means. If we can get to a population of clears that would be terrific.
I just don't think we should eliminate all affecteds and carriers from a breeding program if they have other wonderful attributes. (I don't even breed, so this is mind pursuit actually.)

DLS

I just think they are rated, like type 1, type 2, etc. I will try and find the list which explains all of them. The one we should be most worried about is the same one that affect hemopheliacs{sp.}, gad my spelling is atrocious {haha, I looked up the spelling for that one}. I just remember that years ago a lot of breeders removed dogs from their breeding program because the tests they thought were conclusive for vWD, were not. I do believe testing is a good idea, but I want to be sure that the tests available are really addressing the issues and will indeed be helping the future of our breed.

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DLS

OK, here is some more info on vWD. It refers to the disorder in humans, but I would think it is the same for dogs. Maybe a Vet here could confirm this.




von Willibrand's Disease
This is the commonest hereditary coagulopathy in humans. It can be congenital or acquired. It was described in 1926 by Erik von Willebrand in inhabitants of the Aland Islands in the Sea of Bothnia between Sweden and Finland. It was called pseudohemophilia but later became known as vascular haemophilia.

Pathophysiology
Von Willebrand's disease results from the deficiency or abnormal function of von Willebrand Factor (vWF). vWF is a multimeric glycoprotein encoded for by gene map locus 12p13.1 It is made in the endothelium and stored in Weibel-Palade bodies. It has two main functions:

Assists in platelet plug formation by attracting circulating platelets to the site of damage
Binds to coagulation factor VIII preventing its clearance from the plasma
Epidemiology
Prevalence as high as 1-2% in the general population on unselected screening
Worldwide incidence is around 125 per million with between 0.5 and 5 per million being severely affected
Most patients have mild disease
Commoner in females
More severe with blood type O
Presentation
This varies according to the extent of the deficiency

Bleeding tendency from mucosa e.g. epistaxis, menorrhagia (consider in women with no other obvious cause)
Spontaneous bleeding e.g. internal or joint bleeding (only in severest of cases)
Blood clots during childbirth (rare)
Death may occur
Causes
Hereditary - 3 types (see below)
Acquired - also called Pseudo-von Willebrand's disease or platelet-type; causes include2
Autoantibody formation which binds vWF and results in rapid clearance of it from the circulation
Aortic stenosis - rarely can develop Heyde's syndrome resulting in vWD and predisposes to gastrointestinal bleeding
Others - Wilm's tumour, hypothyroidism
Classification of hereditary typesTypes of hereditary von Willebrand's disease(vWD)
Type of vWD Epidemiology - percentage of all cases Quantitative or Qualitative defect Genetics Presentation
***{THIS IS THE ONLY ONE OUR CURRENT DNA TESTS FOR IN DOBERMAN }***Type 1 60-80% Quantitative defect (19-45% of enzyme level present) Heterozygous for defective gene

Inherited as AD
Normal life span

Occasionally easy bruising and/or menorrhagia

Bleeding after dental work, major surgery

Type 2 20-30% Qualitative defect - multimers abnormal or subgroups absent Usually AD inheritance (rarely AR)
Bleeding tendency varies

4 subtypes: 2A, 2B, 2M, 2N

Type 3 Rare - most severe form; 1-5% of cases Quantitative - levels very low or undetectable Homozygous for defective gene

AR inheritance

No vWF antigen

Low factor VIII
Severe mucosal bleeding

May have haemarthrosis (as in haemophilia)

Platelet type Rare; less than 70 cases described Functional mutations of vWF receptor on platelet Autosomal dominant


Type 1 60-80% Quantitative defect (19-45% of enzyme level present) Heterozygous for defective gene
Inherited as AD
Normal life span
Occasionally easy bruising and/or menorrhagia
Bleeding after dental work, major surgery
Type 2 20-30% Qualitative defect - multimers abnormal or subgroups absent Usually AD inheritance (rarely AR)
Bleeding tendency varies
4 subtypes: 2A, 2B, 2M, 2N
Type 3 Rare (1-5% of cases) - most severe form.
Quantitative - levels very low or undetectable Homozygous for defective gene
Autosomal recessive inheritance
No vWF antigen, Low factor VIII
Severe mucosal bleeding, may have haemarthrosis (as in haemophilia)
Platelet type - Rare (less than 70 cases described)
Functional mutations of vWF receptor on platelet
Autosomal dominant
Subtypes of type 2
Type 2A
Abnormal synthesis or proteolysis of vWF multimers
Leads to small multimers in circulation; factor VIII still binds as normal
Type 2B
Spontaneous binding of platelets with rapid clearance of platelets and large vWF multimers
Mild thrombocytopaenia
Factor VIII binding normal or low normal
Desmopressin will not help as leads to unwanted platelet aggregation
Type 2M
Low or absent binding to receptor on platelets
Factor VIII binds as normal
Investigations
Bloods including full blood count, fibrinogen level, platelet count, clotting screen, factor IX levels
Plasma levels of vWF - keep in mind that deficiency can be qualitative or quantitative
Quantitative deficiency - detected by vWF antigen assay
Qualitative deficiency - detected by a number of methods including glycoprotein binding assay, ristocetin cofactor activity, ristocetin induced platelet agglutination3
Factor VIII measurement - factor VIII binds to vWF which in turn prevents the rapid breakdown of factor VIII; thus a deficiency of vWF can also lead to deficiency of factor VIII
In type 2 vWF - factor VIII levels are normal; studies of platelet aggregation with subendothelium are necessary


Oestrogens, vasopressin and growth hormone all elevate levels.

Pregnancy and vWD
In pregnancy the levels of vWF increase, even in type III and there is usually no problem with labour and delivery but there may be problems in the first week or two postpartum.

Management
No regular therapy required4
Educate patients as to bleeding risk which depends upon level and type of deficiency
In some mild cases desmopressin can be given which will enhance vWF and factor VIII levels by inducing its release from storage in the endothelial cells
Desmopressin is first line in Type I vWD, in all other types factor VIII - vWF concentrates are first line. If the response to the first line agents is poor then the other can be tried as an alternative (not in type 3).5
Desmopressin is ineffective in type 3 as there is no vWF levels to boost
For major procedures prophylactic factor VIII complexed to vWF can be used. This can be found in fresh frozen plasma however the amount required may be associated with volume overload. Cryoprecipitate can also be used and only 8-12 bags are required.
Patients who have alloantibodies to vWF will require recombinant factor VIII5
More therapies
Humate-P (novel) - contains antihaemophilic factor
Antifibrinolytic antibodies e.g. aminocaproic acid or traxenamic acid may also help


--------------------------------------------------------------------------------
Document References
OMIM - vWD
Tefferi A, Nichols WL; Acquired von Willebrand disease: concise review of occurrence, diagnosis, pathogenesis, and treatment. Am J Med. 1997 Dec;103(6):536-40. [abstract]
Chalmers EA; Neonatal coagulation problems. Arch Dis Child Fetal Neonatal Ed. 2004 Nov;89(6):F475-8. [abstract]
Hampton KK, Preston FE; ABC of clinical haematology. Bleeding disorders, thrombosis, and anticoagulation. BMJ. 1997 Apr 5;314(7086):1026-9.
Mannucci PM; Treatment of von Willebrand's Disease. N Engl J Med. 2004 Aug 12;351(7):683-94.

--------------------------------------------------------------------------------
Internet and Further Reading
Hamophilia Society von Willebrands leaflet
Acknowledgements EMIS is grateful to Dr Gurvinder Rull for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2007.

__________________
There are other fine dogs; then there are Dobermann - the dog of dogs!
www.nopupppymillscanada.ca
www.dobermanassistance.org. www.dobermannrescue.org http://www.doberman911.org:80/seniors/

alwayshadpets

My Heidi died from a bleeding disorder that was not VWD. It was thrombocytopenia. She was diagnosed at 4 and we had to put her down at at 5. After going through that I will only have a clear rated doberman. I don`t want to be anywhere near the heartache that any bleeding disorder can cause a family. Once in a lifetime is enough.
My other dobes died of cancer.

reddobes

I just want to reiterate what some have already said and that is there are numerous things that can cause decreased clotting ability. Von Willebrand's is just one of those and one of the less common. And just because a dog/bitch has increased bleeding from a surgery, this does NOT mean the dog has vWD.
Just a few of the other causes of decreased clotting:
Estrus
Tick borne diseases - Anaplasma, Ehrlichia, etc
Thrombocytopenia (decreased platelets - often immune-mediated)
Toxins - rat/mouse poison
Liver disease
other clotting factor deficiency
bone marrow cancer
DIC

CoAl-s-Mom

What's DIC, reddobes?

DLS

CoAL-s-Mom, I can't remember the medical terminology of DIC, it has something to do with all the body systems shutting down {there are many medical reasons why this happens} Some of us just take it as meaning Death Is Comming. I know this is not the correct explanation, but it is what happens.
I am sure reddobes or one of the Vets on this site can give a better meaning for the term DIC.

__________________
There are other fine dogs; then there are Dobermann - the dog of dogs!
www.nopupppymillscanada.ca
www.dobermanassistance.org. www.dobermannrescue.org http://www.doberman911.org:80/seniors/

reddobes

DIC = Disseminated Intravascular Coagulopathy

Disseminated intravascular coagulation - Wikipedia, the free encyclopedia

It's very bad and most don't recover from it. I have had 1 patient that pulled thru w/ intensive therapy, but it is often referred to by vets as "dead in cage" (or "death is coming" in human medicine), as it is often fatal.

CoAl-s-Mom

Thanks for the explanations. Sounds horrible and I hope I never have to learn more about it.

LCalypso

VetGen has a great description of how vWD switch genes work.As only 16-20% of the population are clear we would be losing valuable genetic diversity if selection were limited strictly by vWD status.Of coarse a affected should never be bred.I would not risk my animal by doing so.Ethical standards should dictate clear to clear or clear to carrier only---Provided the carrier has something valuable to offer