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The Relationship between Thyroid Function and von Willebrand's' Disease

W. Jean Dodds, D.V.M.
Division of Laboratories and Research
New York State Department of Health
Empire State Plaza
Albany, New York 12201

Supported in part by NIH grant HLO9902 from the National Heart, Lung, and Blood Institute, PHS/DHHS and by grants from the Geraldine R. Dodge Foundation and the American Kennel Club.

The high prevalence of both hypothyroidism and von Willebrand's disease in the Doberman Pinscher, suggests a casual relationship with respect to the synthesis and/or metabolic regulation of thyroid hormones and the von Willebrand's factor protein (VVTF). The latter protein is deficienteor abnormal in von Willebrand's disease (%TWD), a condition in which affected animals and humans express a bleeding tendency caused by abnormal platelet function and blood coagulation. VWD has been recognized in 27 dog breeds to date and the prevalence of the gene, in those breeds where significant numbers have been studied, varies from 15 to about 60%. Currently, the VWD gene is present in 59% of the Doberman pinscher stock tested throughout North America(over 3000 dogs have been checked). Similarly, hypothyroidism is recognized as an important clinical and sub-clinical entity in this breed.

Another interesting finding relevant to the demographics of VWD and thyroid function has been a series of reports concerning changes observed in platelet function and coagulation factors, especially factor VIII activity and VWF, in human patients with thyroid disease (3-5). For example, the literature reports studies of 61 hypothyroid patients in which 51 of them had abnormal platelet function, or low factor VIII activity and low VWF. In 4 patients studied recently, 3 had significant improvement in their factor VIII activity and VWF level upon oral thyroid treatment. Similarly, in hyp@rthyroidism 49 patients have been studied and of these 44 had increased levels of the above clotting factors. Anti-thyroid treatment resulted in return to normal values for 8 of 9 patients within 3 weeks. Altering thyroid levels in healthy people also affects factor VIII levels as well as fibrinogen. With respect to our studies of Dobermans affected with or carrying VWD, we have found an increased frequency and severity of bleeding episodes in those animals that are also hypothyroid. Retrospective studies of 3 large, inbred families of Dobermans with VWD and many (over 200) isolated cases of VWD in this breed indicate a relationship between the reduced levels of T and/or 4 T3 and %TWF and the number and degree of stress-induced bleeding episodes. Clinical signs of bleeding have been lessened or controlled within 48 hours after initiation of thyroid supplementation [ L-thyroxine, (Synthyroid)).,In one family of 77 members, 38 have shown clinical signs of thyroid disease and have reduced T4 and/or T3. Thirty-nine family members have been tested for VWD and 16 had normal thyroid function and normal levels of VWF. By contrast 23 of them were hypothyroid and their levels of VWF varied from 0 (undetectable) to 46%.

To date, we have performed four controlled studies of the relationship between thyroid function and VWF level. Two of these studies involved normal dogs supplemented for 44 days with either T or T Serial monitoring of their 43thyroid and VWF levels revealed no change over pretreatment levels in VWF despite the expected dramatic increases in T4 and T31 respectively. Addition of the drug, propranolol, to the regimen for 2 weeks -- to block potentia contributing effects of the adrenal glands -- did not alter results. By contrast, when 7 Doberirans with VWD and @erline to mild hypothyroidism were treated with T4 supplementation, there was a 2 to 3-fold increase in their baseline VWF levels which peaked at day 3 and remained high for another 3-4 days. Subsequentlylevels fluctuated in a regular, cyclical manner every 5-7 days throughout the observation period. These cycles of increased VWF coincided with increases in circulating levels of T4' Despite increases over the pretreatment levels of VWF, levels in affected dogs, with one exception, never approached the normal range. In one animal, the baseline level of 36-45% VWF became normalized on thyroid treatment (60-95%). Thus, animals with thyroid dysfunction can have fluctuating levels of VWF and,when they are on thyroid supplementation, levels may be within normal limits which could preclude an accurate diagnosis of their genetic- status for VKTD (ie. carriers of VWD min t test as clear)

In summary, both clinical and experimental observations in man and the Doberman pinscher indicate a significant relationship between thyroid function and the bleeding tendency and laboratory abnormalities associated with VWD, It is important for all Doberman breeders and veterinarians to measure thyroid function in their breeding stock (even if there are no obvious clinical signs of thyroid disease) and, especially in those dogs known to be carriers of VWD or related to carriers of VI@TD. For Dobermans affected with clinical signs of bleeding, the veterinarian should measure thyroid function as well as test for VWD. Many affected dogs also have low platelet counts which will aggravate their bleeding tendency. If the bleeding is severe, immediate treatment with T4 (Synthroid) should be given to help control the problem until the results of the thyroid and blood tests are completed. If thyroid function turns out to be normal, treatment can be stopped and, if not, it needs to be continued for the rest of the dog's life. In that regard, Doberman breeders need to be more cautious about breeding dogs with hypothyroidism. There is clearly a familial predisposition to this defect in the breed and continual matings where both parents are hypothyroid are bound to increase the frequency of this undesirable problem. Responsible breeders should, therefore, begin to select against hypothyroidism amongst their breeding stock. The most effective way to do this is to breed only those with mild thyroid disease and to choose for them mates that have normal thyroid function.

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