Klinefelter’s syndrome: Associations with increased blood clotting (thrombosis) events (deep venous thrombosis, pulmonary embolus, venous thromboembolism).
New Research Protocol: Free consultation and evaluation.
Charles J. Glueck MD, Jewish Hospital of Cincinnati, 2135 Dana Avenue, Cincinnati OH, 45207. Email cjglueck@mercy.com, Phone 513-924-8250; Fax 513-924-8273.
The close association of Klinefelter’s syndrome with unexplained thrombosis has been known for at least 33 years [1-7]. Venous thromboemboli (VTE) are ~20 fold more frequent in Klinefelter’s syndrome than in the general population [3]. Previous single case studies of Klinefelters with VTE have found Protein C deficiency [4], Lupus anticoagulant and anticardiolipin antibodies [6], and protein S deficiency, homocysteinemeia, the lupus anticoagulant[8], Factor V Leiden Heterozygosity, Prothrombin gene 20210A heterozygosity, high Factor VIII and high Factor XI[9] .
In our most recent publications, of 67 patients with VTE after taking testosterone, 6 had Klinefelters treated with testosterone replacement therapy [1, 9]. The uniform normal practice to treat the testostosterone deficiency of Klinefelters syndrome is with exogenous testosterone. Since exogenous testosterone can interact with previously undiagnosed thrombophilias to produce VTE [9], there is a reasonable likelihood that the VTE observed in Klinefelters cases does not represent some unique prothrombotic characteristic of Klinefelters itself, but reflects the thrombotic effects of uniform testosterone supplementation interacting with an inherited or acquired increased tendency to form blood clots (thrombophilia) in a group which may also be enriched with familial thrombophilia.
Take Action: If you have a well-defined diagnosis of Klinefelters syndrome, and have had VTE while taking testosterone therapy, you may have a high likelihood of having an inherited or acquired thrombophilia. We would be glad to assist you as follows to participate in a new research protocol:
First: Any and all information you provide us is entirely confidential, covered by HIPAA regulations and will never be released to anyone else without your original signature permission.
Second: We will share all of our information with you and your designated physicians.
Third:
1. If you can get to Cincinnati for a FREE 1 hour outpatient consultation, we will obtain the appropriate blood tests for thrombophilia, as well as evaluate your case, and make recommendations for future therapy.
2. If you cannot get to Cincinnati for the free 1 hour outpatient consultation, we will, FREE OF CHARGE, provide the necessary laboratory orders for the appropriate blood tests for thrombophilia, evaluate your case, and make recommendations for future therapy. However, your health insurance will have to cover the costs of the laboratory testing for thrombophilia, and unless your health policy covers these costs, they would be very very expensive for you to pay by yourself. If you already have laboratory results for thrombophilia, we will be glad, FREE OF CHARGE, to evaluate them and make recommendations.
References
1. Glueck CJ, Wang P. Testosterone therapy, thrombosis, thrombophilia, cardiovascular events. Metabolism. 2014;63:989-94.
2. Kang BS, Cho DK, Koh WJ, et al. A case of severe pulmonary thromboembolism in a young male with klinefelter syndrome. Korean Circ J. 2012;42:562-4.
3. Kluge JG, Korner I, Kluge G, Froster U, Pfeiffer D. [35-year old patient with severe thromboembolism]. Internist (Berl). 2010;51:1567-70.
4. Angel JR, Parker S, Sells RE, Atallah E. Recurrent deep vein thrombosis and pulmonary embolism in a young man with Klinefelter's syndrome and heterozygous mutation of MTHFR-677C>T and 1298A>C. Blood Coagul Fibrinolysis. 2010;21:372-5.
5. Ayli M, Ertek S. Serious venous thromboembolism, heterozygous factor V Leiden and prothrombin G20210A mutations in a patient with Klinefelter syndrome and type 2 diabetes. Intern Med. 2009;48:1681-5.
6. Lapecorella M, Marino R, De Pergola G, Scaraggi FA, Speciale V, De Mitrio V. Severe venous thromboembolism in a young man with Klinefelter's syndrome and heterozygosis for both G20210A prothrombin and factor V Leiden mutations. Blood Coagul Fibrinolysis. 2003;14:95-8.
7. Wautrecht JC, Vincent G, Dereume JP. [Venous thromboembolic disease and Klinefelter's syndrome]. J Mal Vasc. 1986;11:125-7.
8. Kasten R, Pfirrmann G, Voigtlander V. [Klinefelter's syndrome associated with mixed connective tissue disease (Sharp's syndrome) and thrombophilia with postthrombotic syndrome]. J Dtsch Dermatol Ges. 2005;3:623-6.
9. Glueck CJ, Prince M, Patel N, et al. Thrombophilia in 67 Patients With Thrombotic Events After Starting Testosterone Therapy.Clin Appl Thromb Hemost. 2015 Nov 30. pii: 1076029615619486. [Epub ahead of print Clin Appl Thromb Hemost. 2015.]
New Research Protocol: Free consultation and evaluation.
Charles J. Glueck MD, Jewish Hospital of Cincinnati, 2135 Dana Avenue, Cincinnati OH, 45207. Email cjglueck@mercy.com, Phone 513-924-8250; Fax 513-924-8273.
The close association of Klinefelter’s syndrome with unexplained thrombosis has been known for at least 33 years [1-7]. Venous thromboemboli (VTE) are ~20 fold more frequent in Klinefelter’s syndrome than in the general population [3]. Previous single case studies of Klinefelters with VTE have found Protein C deficiency [4], Lupus anticoagulant and anticardiolipin antibodies [6], and protein S deficiency, homocysteinemeia, the lupus anticoagulant[8], Factor V Leiden Heterozygosity, Prothrombin gene 20210A heterozygosity, high Factor VIII and high Factor XI[9] .
In our most recent publications, of 67 patients with VTE after taking testosterone, 6 had Klinefelters treated with testosterone replacement therapy [1, 9]. The uniform normal practice to treat the testostosterone deficiency of Klinefelters syndrome is with exogenous testosterone. Since exogenous testosterone can interact with previously undiagnosed thrombophilias to produce VTE [9], there is a reasonable likelihood that the VTE observed in Klinefelters cases does not represent some unique prothrombotic characteristic of Klinefelters itself, but reflects the thrombotic effects of uniform testosterone supplementation interacting with an inherited or acquired increased tendency to form blood clots (thrombophilia) in a group which may also be enriched with familial thrombophilia.
Take Action: If you have a well-defined diagnosis of Klinefelters syndrome, and have had VTE while taking testosterone therapy, you may have a high likelihood of having an inherited or acquired thrombophilia. We would be glad to assist you as follows to participate in a new research protocol:
First: Any and all information you provide us is entirely confidential, covered by HIPAA regulations and will never be released to anyone else without your original signature permission.
Second: We will share all of our information with you and your designated physicians.
Third:
1. If you can get to Cincinnati for a FREE 1 hour outpatient consultation, we will obtain the appropriate blood tests for thrombophilia, as well as evaluate your case, and make recommendations for future therapy.
2. If you cannot get to Cincinnati for the free 1 hour outpatient consultation, we will, FREE OF CHARGE, provide the necessary laboratory orders for the appropriate blood tests for thrombophilia, evaluate your case, and make recommendations for future therapy. However, your health insurance will have to cover the costs of the laboratory testing for thrombophilia, and unless your health policy covers these costs, they would be very very expensive for you to pay by yourself. If you already have laboratory results for thrombophilia, we will be glad, FREE OF CHARGE, to evaluate them and make recommendations.
References
1. Glueck CJ, Wang P. Testosterone therapy, thrombosis, thrombophilia, cardiovascular events. Metabolism. 2014;63:989-94.
2. Kang BS, Cho DK, Koh WJ, et al. A case of severe pulmonary thromboembolism in a young male with klinefelter syndrome. Korean Circ J. 2012;42:562-4.
3. Kluge JG, Korner I, Kluge G, Froster U, Pfeiffer D. [35-year old patient with severe thromboembolism]. Internist (Berl). 2010;51:1567-70.
4. Angel JR, Parker S, Sells RE, Atallah E. Recurrent deep vein thrombosis and pulmonary embolism in a young man with Klinefelter's syndrome and heterozygous mutation of MTHFR-677C>T and 1298A>C. Blood Coagul Fibrinolysis. 2010;21:372-5.
5. Ayli M, Ertek S. Serious venous thromboembolism, heterozygous factor V Leiden and prothrombin G20210A mutations in a patient with Klinefelter syndrome and type 2 diabetes. Intern Med. 2009;48:1681-5.
6. Lapecorella M, Marino R, De Pergola G, Scaraggi FA, Speciale V, De Mitrio V. Severe venous thromboembolism in a young man with Klinefelter's syndrome and heterozygosis for both G20210A prothrombin and factor V Leiden mutations. Blood Coagul Fibrinolysis. 2003;14:95-8.
7. Wautrecht JC, Vincent G, Dereume JP. [Venous thromboembolic disease and Klinefelter's syndrome]. J Mal Vasc. 1986;11:125-7.
8. Kasten R, Pfirrmann G, Voigtlander V. [Klinefelter's syndrome associated with mixed connective tissue disease (Sharp's syndrome) and thrombophilia with postthrombotic syndrome]. J Dtsch Dermatol Ges. 2005;3:623-6.
9. Glueck CJ, Prince M, Patel N, et al. Thrombophilia in 67 Patients With Thrombotic Events After Starting Testosterone Therapy.Clin Appl Thromb Hemost. 2015 Nov 30. pii: 1076029615619486. [Epub ahead of print Clin Appl Thromb Hemost. 2015.]
