 Is the most common inherited bleeding
disorder in dogs. At least 50 breeds are known to be affected. There is
a particularly high prevalence in Dobermanns, Scottish terriers and Shetland
sheepdogs. The disease is characterized by a lack of functional von
Willebrand factor (vWF) which results in defective Primary
haemostasis and prolongation of bleeding time.
VWF antigen is a multimeric plasma glycxoprotein. It plays
a pivotal role in the adhesion and aggregation of platelets to damaged
vessel wall. In plasma it forms a non-covalent complex with coagulation
Factor VIII. The high molecular weight multimers of vWF are the most
efficient in promoting platelet aggregation. The net result of either an
absolute (quantitative) deficiency of vWF or a preferential
(qualitative) deficiency of the high molecular weight multimers
of vWF is therefore defective platelet adhesion and aggregation.
Classification of von Willebrand’s disease
Von willebrand’s disease is classified as Type 1, Type 2 or Type 3.
The Type 2 and Type 3 forms of the disease will not be discussed here.
Type 1 vWD, which is the form that occurs in Dobermanns, is characterized
by a reduction in the plasma concentration of all multimer sizes.
Clinical signs: The clinical
severity of the Type 1 form correlates with the plasma vWF antigen concentration.
Compared to the Type 2 and Type 3 forms of the disease this tends
to be a relatively mild disorder and clinical signs may only be apparent
following trauma or an elective surgical procedure. Dogs with a bleeding
tendency are often those with vWF antigen concentrations less than
20% of normal.
The most common clinical signs of vWD are mucosal or cutaneous
haemorrhage, haematuria, prolonged bleeding from traumatic or surgical
wounds, bleeding from the gums (especially when deciduous teeth are lost),
epistaxis (nose bleeds), or prolonged bleeding at oestrus.
Pinpoint petechial haemorrages on mucosal surfaces are rarely seen with
vWD. Any bleeding tendency may be exacerbated by thrombocytopenia
(decreased number of platelets in the circulation), drug administration
(non-steroidal anti-inflammatory drugs, sulphonamides), and other diseases
which interfere with platelet function (uraemia, hyperproteinaemia,
anaemia and liver disease). Hypothyroidism has also been associated
with expression of vWD.
Laboratory Findings: Dogs with
vWD have normal platelet counts. Buccal mucosal bleeding time (BMBT)
of clinically affected animals is prolonged (Type 1: 5-10 minutes;
normal 2-4 minutes). Heterozygote carriers usually have normal BMBT.
BMBT is therefore a useful and quick presurgical screening test for detecting
affected homozygotes in situations where insufficient time is available
to measure vWF antigen. Clotting times (OSPT, APTT and ACT) are usually
also normal.
Diagnosis of Type 1 vWD: Requires
the quantitative measurement of vWF antigen using an enzyme-linked immunosorbent
assay (ELISA). Affected homozygote dogs have plasma vWF concentrations
between 5% and 20% of normal (normal: 75%-170%). Heterozygote
carriers usually have plasma vWF concentrations less than 50% of normal
(30%-50%) but some carriers can have vWF concentrations of
50%-75% of normal making it difficult to differentiate these carriers
from unaffected dogs on the basis of vWF antigen bioassay alone.
Sample Collection: Blood should
be collected into citrate anticoagulant (3.8% Na citrate). The ratio
of citrate to whole blood is critical (1 part citrate to 9 parts
of blood i.e. 0.3 ml citrate to 2.7 ml blood = total sample of 3 ml).
Blood can be collected directly into a sodium citrate vacutainer tube,
ensuring that a whole draw is obtained. The concentration of VWF antigen
may be artificially depleted if blood is collected into a 'dry' plastic
syringe before it is transferred into the citrate tube (this depletation
is extremely variable but will be more pronounced with poor venepuncture
technique). Plasma should then be separated as soon after collection
as possible, transferred into a plastic tube, and sent on an ice pack
within a styrofoam container. Ideally, samples should be received at the
Lab within 24 hours.
Treatment: Fresh or fresh frozen
plasma provides a source of vWF. In an emergency, or in cases where red
cells are required, fresh whole blood can be transfused (this must
be done within 6 hours of collection). Crossmatching and blood
group typing are advised since repeated transfusions will probably be required.
Canine cryoprecipitate provides a more concentrated source of vWF
but is not readily available. In an emergency situation desmopressin can
be given subcutaneously. This stimulates the release of vWF from endothelial
stores and temporarily increases vWF activity in Type 1 vWD. It can
also be administered to normal donor dogs to ‘boost’ vWF
levels prior to blood collection.
Genetic Screening: DNA testing
is now available for screening Dobermanns for Type 1 vWD in the UK. It provides
an accurate means of classifying dogs with equivocal vWF results ie
for
differentiating heterozygote carriers of vWD from non-affected dogs. |