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We compared thrombophilia and hypofibrinolysis in 6 men with Klinefelter syndrome (KS), without previously known familial thrombophilia, who had sustained deep venous thrombosis (DVT)–pulmonary emboli (PE) or mesenteric artery thrombosis on testosterone replacement therapy (TRT). After the diagnosis of KS, TRT had been started in the 6 men at ages 11, 12, 13, 13, 19, and 48 years. After starting TRT, DVT-PE or mesenteric artery thrombosis was developed in 6 months, 1, 11, 11, 12, and 49 years. Of the 6 men, 4 had high (&gt;150%) factor VIII (177%, 192%, 263%, and 293%), 3 had high (&gt;150%) factor XI (165%, 181%, and 193%), 1 was heterozygous for the factor V Leiden mutation, and 1 was heterozygous for the G20210A prothrombin gene mutation. None of the 6 men had a precipitating event before their DVT-PE. We speculate that the previously known increased rate of DVT-PE and other thrombi in KS reflects an interaction between prothrombotic, long-term TRT with previously undiagnosed familial thrombophilia. Thrombophilia screening in men with KS before starting TRT would identify a cohort at increased risk for subsequent DVT-PE, providing an optimally informed estimate of the risk/benefit ratio of TRT.

clinical and applied thrombosis/hemostasis

Thrombophilia in Klinefelter Syndrome With Deep Venous Thrombosis, Pulmonary Embolism, and Mesenteric Artery Thrombosis on Testosterone Therapy: A Pilot Study