| Hereditary Basset Thrombopathy . . . 25 Years Later by James L. Catlfamo, Ph.D., and Marjory B. Brooks, D.V.M. This article was originally published in the November-December 1997 issue of Tally-Ho and is reprinted by permission of the authors. |
Twenty five years have passed since Dr. Lotz had the opportunity to study, at Guelph University, a family of Basset Hounds
with an unknown bleeding disorder. The intervening years have been ones of significant progress in understanding this disease.
This brief summary of the progress is an attempt to present the scientific work in a format that is "user friendly" to a
breeder or owner of Basset Hounds.
In 1972, Dr. Lotz presented preliminary data at a scientific conference which suggested that the bleeding he observed in a
family of Canadian Basset Hounds was associated with abnormal platelet function. Platelets are very small cells that circulate
in blood in large numbers and are essential for formation of a "plug" at the site of blood vessel injury. His work was further
expanded in the late 1970s when Johnstone and Lotz presented data confirming the preliminary findings and additional data
which further clarified the functional features of this very interesting platelet defect including the failure of these
platelets to respond to normal stimuli. Today when we screen for platelet function in a Basset Hound we examine their
platelet's responsiveness to two major stimuli, ADP (adenosine diphosphate) and collagen which is a component of the lining of
blood vessels.
During the same time period Dr. W. Jean Dodds and colleagues at the New York State Department of Health also identified
Basset Hounds in the U.S. with similar bleeding problems. They requested and received grant support from the National
Institutes of Health to maintain a research colony. In 1981 studies began, under the direction of Dr. Catalfamo, to
characterize the inherited defect in detail. At that time breeders began to bring their animals to the laboratory in Albany for
platelet function testing. This testing service provided information to the breeder and also identified Basset Hounds with
the severe form of the defect. Some of these animals were donated to the research facility in Albany to participate in the
non-invasive research described in the next paragraph. No Bassets with the defect were were bred at the NYS Department
of Health. All the donated Bassets were maintained for their natural lives. At the present time two Bassets with the defect
are maintained in the research colony. When Drs. Catalfamo and Brooks relocated to Cornell University's College of
Veterinary Medicine in 1994, the two Basset Hounds moved with them into a new state of the art facility. One of the two
relocated Bassets is now 14 years old; she participated in some of the original studies. We continue to offer testing for
thrombopathy on a fee for service basis. At the present time we have no plans to acquire affected Bassets for the research
colony.
The work of the laboratory in Albany and now at Cornell established that Basset Hound thrombopathy was a bleeding disorder
distinct from other inherited bleeding problems such as hemophilia or von Willebrand's disease, which are also present in the
breed. It should be noted that Von Willebrand's is much more common than hemophilia in this breed. The most comprehensive
functional and biochemical characterization of the platelet defect to date was presented in a series of papers authored and
published by Drs. Catalfamo, Boudreux, and Dodds in the mid-1980s. Their studies showed that Basset Hounds with the defect
have an abnormality in the activity of an enzyme involved in regulating cyclic nucleotide metabolism. The ability of this enzyme
to maintain and regulate the level of key components is essential for platelets to function normally. When the levels are
inadequately regulated as is the case in Basset Hounds with thrombopathia then their platelets fail to respond to agents such
as ADP and collagen which trigger (signal) necessary platelet involvement in events that control (stop) bleeding when blood
vessels are injured following trauma or surgery.
This observation could provide the starting point for the future identification of a candidate gene or genes to be used for the
development of a genetic test for the defect. It can also be utilized to provide a more sophisticated and specific testing for
the defect than is currently available with classical methods of platelet aggregometry. These future research goals will be
met when the allocation of financial and scientific resources are sufficient to sustain new research projects.
The third group that has contributed to our understanding of the platelet defect in Basset Hounds is located at Michigan
State University. In the mid '80s Dr. Tom Bell and associates at Michigan also offered a testing program to breeders,
identified a number of severely affected Bassets, and received federal support to study the defect as an animal model. This
group published data on the genetics of the defect, the atypical secretion response of thrombopathic platelets, and their
ability to bind soluble fibringen and interact with adhesive surfaces. They also identified differences in the two-dimensional
electrophoretic patterns of thrombopaathic platelets. On the basis of these differences they attempted to refine the test
used to identify carriers of Basset Hound thrombopathy. At present they offer to breeders limited testing for the defect.
I have compiled a list of suggested papers to read for those who want to wade into a sea of scientific jargon.
Suggested Reading
Lotz F., Crane S. and Downey H.G.; 1972. Proceedings of the Third Congress of Int. Soc. On thrombosis and haemostasis.
Washington, D.C., Abstract, p. 220.
Johnstone I.B., Lotz F; 1979. An Inherited platelet function defect in Basset Hounds. Can Vet J 20:211-15.
Paterson W.R.; Padgett G.A. and Bell T.G.. 1985. Abnormal release of storage pool adenine nucleotides from platelets of dogs
affected with Basset Hound thrombopathy. Thrombosis Res. 37:61-71.
Catalfamo J.L., Raymond S.L., White J.G., and Dodds, W.J. 1986. Defective platelet-fibrinogen interaction in hereditary canine
thrombopathia. Blood:671568-1577.
Mattson J.C., Estry D.W., Bell T.G., and Patterson W.R. 1986. Defective contact activation of platelets from dogs with Basset
Hound hereditary thrombopathy. Thrombosis Res. 44:23-38.
Boudreux, M.K., Dodds W.J., Slauson D.O. and Catalfamo J.L. 1986. Impaired cAMP metabolism associated with abnormal
function of thrombopathic canine platelets. Biochem Biophys Res Commun. 140:595-601.
Boudreux, M.K., Dodds W.J., Slauson D.O. and Catalfamo J.L. 1986. Evidence for regulatory control of canine platelet
phosphodieterase. Biochem Biophys Res Commun. 140:589-594.
Catalfamo J.L. and Dodds W.J. 1988. Hereditary and Acquired Thrombopathias. In Veterinary Clinics of North America. Small
Animal Practice. Ed, Feldman B.F., W.B. Saunders Co. Philadelphia. 18:185-193.
The technical language associated with the scientific papers often makes them of little real value to the breeder or owner of
a Basset Hound. They are best served by a clear and concise interpretation of the scientific literature and an explanation of
its significance to their program or the health of their dog. We hope the frequently asked questions format will be useful.
Frequently Asked Questions
1. How do I know if I have a bleeder?
There are usually clear signs that are recognizable by the owner. The dog may bleed excessively when puppy teeth are shed;
you may see small pinpoint spots on the dog's abdomen that come and go; these spots are signs of capillary bleeding in the skin;
the dog may have nose bleeds that are difficult to control; the dog may bleed on the tips of the ear after contact with a rough
surface; as they get older they may have excessive bleeding around their gums and may have bleeding complications following a
dental extraction; they may show signs of easy bruising; they are most frequently identified as bleeders after they have
undergone a surgical procedure that is associated with bleeding complications. Bassets with mild platelet dysfunction may not
exhibit any of the signs associated with the severe form of the disease. These animals may have only minor or no bleeding
complications following surgery. They have sufficient platelet function to support platelet plug formation and normal clotting.
2. How prevalent is thrombopathia in the breed?
The prevalence of this genetic defect has not been established in the breed. Animals with very mild forms of the disease may
not exhibit overt bleeding signs. They may be noticed as minor complications by your vet when a minor surgical procedure is
performed. The testing done in Albany and now at Cornell has been limited and involves owners who have had an affected dog
or are aware of the disease through breed educational programs. In 1996, approximately 25 Basset Hounds were tested at
Cornell. At the peak of our testing in Albany in the late 1980s the numbers were as high as 200 Basset Hounds tested for
thrombopathia per year. Despite the large numbers tested in the late 1980s, very few entire litters were tested. Often no
data on the platelet function status of the sire was available. This type of random testing did not allow for the establishment
of a data base to reliably predict prevalence. Case consultations with veterinarians seeking advice for management of
bleeding crises in Basset Hounds allowed us to establish that the geographic distribution of the defect is widespread and
includes all regions of the U.S. and Canada. The signs of this disorder are often not recognizable during the early stages of
treatment. This may result in an underestimation and misclassification of the disease.
3. How do I manage my breeding program to avoid the defect?
The very best approach is to breed animals that have had their platelet function evaluated. It is not possible for the breeder
to establish the genetic status of the dog based on the bleeding phenotype. Only dogs with the severest form of the defect
can be identified in that manner. If you have a "bleeder" it should be tested to establish a precise diagnosis for proper
management of the dog. Dogs with intermediate to reduced platelet function are at risk for transmitting the trait for
thrombopathia but not necessarily for expressing the bleeder phenotype. You should avoid breeding a Basset with the severe
form of the disease. If you do decide to breed dogs with the more mild platelet function abnormality then you should breed to
a normal testing Basset and then test the litter and select normal testing litter mates for any future breeding program.
4. How do I distinguish this defect from other bleeding disorders like von Willebrand's disease and hemophilia?
Once your vet has ruled out a possible blood vessel disorder he or she should then evaluate the dog for von Willebrand's
disease or possible inherited or acquired coagulation factor defects like hemophilia or rat poisoning by requesting a PTT and
PT assays. He or she should also evaluate the dog's platelet numbers; if all these tests are normal and the dog continues to
show signs of a bleeding problem then the dog should be referred, if possible, to a specialized center for platelet function
testing. It is best that your veterinarian establish that the dog's bleeding time (cuticle or buccal) is normal before
performing surgical procedures. Transfusion support in the form of whole blood or platelet concentrate should be available
prior to surgery for an animal with a known defect in platelet function and a prolonged bleeding time. In contrast to an animal
with von Willebrand's disease a Basset with severe thrombopathia will not respond to transfusion of plasma alone; they
require functional platelets from a normal donor dog. In contrast to hemophilia where only the males are affected, in
thrombopathia both males and females are affected.
5. If I have a question about a bleeding disorder whom should I contact?
If it's an emergency notify your vet at once and follow his or her advice. You or your vet can call our laboratory at
607-275-0622 or 607-275-0623 and ask for myself or Dr. Brooks. We can help with the diagnostic workup and provide case
management information.
with an unknown bleeding disorder. The intervening years have been ones of significant progress in understanding this disease.
This brief summary of the progress is an attempt to present the scientific work in a format that is "user friendly" to a
breeder or owner of Basset Hounds.
In 1972, Dr. Lotz presented preliminary data at a scientific conference which suggested that the bleeding he observed in a
family of Canadian Basset Hounds was associated with abnormal platelet function. Platelets are very small cells that circulate
in blood in large numbers and are essential for formation of a "plug" at the site of blood vessel injury. His work was further
expanded in the late 1970s when Johnstone and Lotz presented data confirming the preliminary findings and additional data
which further clarified the functional features of this very interesting platelet defect including the failure of these
platelets to respond to normal stimuli. Today when we screen for platelet function in a Basset Hound we examine their
platelet's responsiveness to two major stimuli, ADP (adenosine diphosphate) and collagen which is a component of the lining of
blood vessels.
During the same time period Dr. W. Jean Dodds and colleagues at the New York State Department of Health also identified
Basset Hounds in the U.S. with similar bleeding problems. They requested and received grant support from the National
Institutes of Health to maintain a research colony. In 1981 studies began, under the direction of Dr. Catalfamo, to
characterize the inherited defect in detail. At that time breeders began to bring their animals to the laboratory in Albany for
platelet function testing. This testing service provided information to the breeder and also identified Basset Hounds with
the severe form of the defect. Some of these animals were donated to the research facility in Albany to participate in the
non-invasive research described in the next paragraph. No Bassets with the defect were were bred at the NYS Department
of Health. All the donated Bassets were maintained for their natural lives. At the present time two Bassets with the defect
are maintained in the research colony. When Drs. Catalfamo and Brooks relocated to Cornell University's College of
Veterinary Medicine in 1994, the two Basset Hounds moved with them into a new state of the art facility. One of the two
relocated Bassets is now 14 years old; she participated in some of the original studies. We continue to offer testing for
thrombopathy on a fee for service basis. At the present time we have no plans to acquire affected Bassets for the research
colony.
The work of the laboratory in Albany and now at Cornell established that Basset Hound thrombopathy was a bleeding disorder
distinct from other inherited bleeding problems such as hemophilia or von Willebrand's disease, which are also present in the
breed. It should be noted that Von Willebrand's is much more common than hemophilia in this breed. The most comprehensive
functional and biochemical characterization of the platelet defect to date was presented in a series of papers authored and
published by Drs. Catalfamo, Boudreux, and Dodds in the mid-1980s. Their studies showed that Basset Hounds with the defect
have an abnormality in the activity of an enzyme involved in regulating cyclic nucleotide metabolism. The ability of this enzyme
to maintain and regulate the level of key components is essential for platelets to function normally. When the levels are
inadequately regulated as is the case in Basset Hounds with thrombopathia then their platelets fail to respond to agents such
as ADP and collagen which trigger (signal) necessary platelet involvement in events that control (stop) bleeding when blood
vessels are injured following trauma or surgery.
This observation could provide the starting point for the future identification of a candidate gene or genes to be used for the
development of a genetic test for the defect. It can also be utilized to provide a more sophisticated and specific testing for
the defect than is currently available with classical methods of platelet aggregometry. These future research goals will be
met when the allocation of financial and scientific resources are sufficient to sustain new research projects.
The third group that has contributed to our understanding of the platelet defect in Basset Hounds is located at Michigan
State University. In the mid '80s Dr. Tom Bell and associates at Michigan also offered a testing program to breeders,
identified a number of severely affected Bassets, and received federal support to study the defect as an animal model. This
group published data on the genetics of the defect, the atypical secretion response of thrombopathic platelets, and their
ability to bind soluble fibringen and interact with adhesive surfaces. They also identified differences in the two-dimensional
electrophoretic patterns of thrombopaathic platelets. On the basis of these differences they attempted to refine the test
used to identify carriers of Basset Hound thrombopathy. At present they offer to breeders limited testing for the defect.
I have compiled a list of suggested papers to read for those who want to wade into a sea of scientific jargon.
Suggested Reading
Lotz F., Crane S. and Downey H.G.; 1972. Proceedings of the Third Congress of Int. Soc. On thrombosis and haemostasis.
Washington, D.C., Abstract, p. 220.
Johnstone I.B., Lotz F; 1979. An Inherited platelet function defect in Basset Hounds. Can Vet J 20:211-15.
Paterson W.R.; Padgett G.A. and Bell T.G.. 1985. Abnormal release of storage pool adenine nucleotides from platelets of dogs
affected with Basset Hound thrombopathy. Thrombosis Res. 37:61-71.
Catalfamo J.L., Raymond S.L., White J.G., and Dodds, W.J. 1986. Defective platelet-fibrinogen interaction in hereditary canine
thrombopathia. Blood:671568-1577.
Mattson J.C., Estry D.W., Bell T.G., and Patterson W.R. 1986. Defective contact activation of platelets from dogs with Basset
Hound hereditary thrombopathy. Thrombosis Res. 44:23-38.
Boudreux, M.K., Dodds W.J., Slauson D.O. and Catalfamo J.L. 1986. Impaired cAMP metabolism associated with abnormal
function of thrombopathic canine platelets. Biochem Biophys Res Commun. 140:595-601.
Boudreux, M.K., Dodds W.J., Slauson D.O. and Catalfamo J.L. 1986. Evidence for regulatory control of canine platelet
phosphodieterase. Biochem Biophys Res Commun. 140:589-594.
Catalfamo J.L. and Dodds W.J. 1988. Hereditary and Acquired Thrombopathias. In Veterinary Clinics of North America. Small
Animal Practice. Ed, Feldman B.F., W.B. Saunders Co. Philadelphia. 18:185-193.
The technical language associated with the scientific papers often makes them of little real value to the breeder or owner of
a Basset Hound. They are best served by a clear and concise interpretation of the scientific literature and an explanation of
its significance to their program or the health of their dog. We hope the frequently asked questions format will be useful.
Frequently Asked Questions
1. How do I know if I have a bleeder?
There are usually clear signs that are recognizable by the owner. The dog may bleed excessively when puppy teeth are shed;
you may see small pinpoint spots on the dog's abdomen that come and go; these spots are signs of capillary bleeding in the skin;
the dog may have nose bleeds that are difficult to control; the dog may bleed on the tips of the ear after contact with a rough
surface; as they get older they may have excessive bleeding around their gums and may have bleeding complications following a
dental extraction; they may show signs of easy bruising; they are most frequently identified as bleeders after they have
undergone a surgical procedure that is associated with bleeding complications. Bassets with mild platelet dysfunction may not
exhibit any of the signs associated with the severe form of the disease. These animals may have only minor or no bleeding
complications following surgery. They have sufficient platelet function to support platelet plug formation and normal clotting.
2. How prevalent is thrombopathia in the breed?
The prevalence of this genetic defect has not been established in the breed. Animals with very mild forms of the disease may
not exhibit overt bleeding signs. They may be noticed as minor complications by your vet when a minor surgical procedure is
performed. The testing done in Albany and now at Cornell has been limited and involves owners who have had an affected dog
or are aware of the disease through breed educational programs. In 1996, approximately 25 Basset Hounds were tested at
Cornell. At the peak of our testing in Albany in the late 1980s the numbers were as high as 200 Basset Hounds tested for
thrombopathia per year. Despite the large numbers tested in the late 1980s, very few entire litters were tested. Often no
data on the platelet function status of the sire was available. This type of random testing did not allow for the establishment
of a data base to reliably predict prevalence. Case consultations with veterinarians seeking advice for management of
bleeding crises in Basset Hounds allowed us to establish that the geographic distribution of the defect is widespread and
includes all regions of the U.S. and Canada. The signs of this disorder are often not recognizable during the early stages of
treatment. This may result in an underestimation and misclassification of the disease.
3. How do I manage my breeding program to avoid the defect?
The very best approach is to breed animals that have had their platelet function evaluated. It is not possible for the breeder
to establish the genetic status of the dog based on the bleeding phenotype. Only dogs with the severest form of the defect
can be identified in that manner. If you have a "bleeder" it should be tested to establish a precise diagnosis for proper
management of the dog. Dogs with intermediate to reduced platelet function are at risk for transmitting the trait for
thrombopathia but not necessarily for expressing the bleeder phenotype. You should avoid breeding a Basset with the severe
form of the disease. If you do decide to breed dogs with the more mild platelet function abnormality then you should breed to
a normal testing Basset and then test the litter and select normal testing litter mates for any future breeding program.
4. How do I distinguish this defect from other bleeding disorders like von Willebrand's disease and hemophilia?
Once your vet has ruled out a possible blood vessel disorder he or she should then evaluate the dog for von Willebrand's
disease or possible inherited or acquired coagulation factor defects like hemophilia or rat poisoning by requesting a PTT and
PT assays. He or she should also evaluate the dog's platelet numbers; if all these tests are normal and the dog continues to
show signs of a bleeding problem then the dog should be referred, if possible, to a specialized center for platelet function
testing. It is best that your veterinarian establish that the dog's bleeding time (cuticle or buccal) is normal before
performing surgical procedures. Transfusion support in the form of whole blood or platelet concentrate should be available
prior to surgery for an animal with a known defect in platelet function and a prolonged bleeding time. In contrast to an animal
with von Willebrand's disease a Basset with severe thrombopathia will not respond to transfusion of plasma alone; they
require functional platelets from a normal donor dog. In contrast to hemophilia where only the males are affected, in
thrombopathia both males and females are affected.
5. If I have a question about a bleeding disorder whom should I contact?
If it's an emergency notify your vet at once and follow his or her advice. You or your vet can call our laboratory at
607-275-0622 or 607-275-0623 and ask for myself or Dr. Brooks. We can help with the diagnostic workup and provide case
management information.
| This site was created by and is maintained by Belinda Winters for BFH Bassets. If you have any questions or comments email belindawinters@bfhbassets.com |
