Severe venous thromboembolism in a young man with Klinefelter's syndrome and heterozygosis for both G20210A prothrombin and factor V Leiden mutations

Abstract

Klinefelter's syndrome is the most common cause of primary testicular failure, resulting in impairment of both spermatogenesis and testosterone production. It is a chromosomal disorder characterized by small, firm testes, azoospermia, gynecomastia, varying degrees of eunuchoidism and testosterone deficiency with elevated gonadotropin plasma levels. In Klinefelter's syndrome there is an increase of certain systemic diseases including venous thromboembolism. An increased thromboembolic risk in hypogonadic men has been explained with hypofibrinolysis due to androgen deficiency. Only two cases have been reported about the association between Klinefelter's syndrome and well-known congenital or acquired thrombophilias. We report the case of a 39-year-old patient with Klinefelter's syndrome who underwent severe deep venous thrombosis with pulmonary embolism, in the absence of any circumstantial triggering event. Further examinations also showed a double heterozygosis for G20210A prothrombin and factor V Leiden mutations. This case suggests that the increased thromboembolic risk, reported in Klinefelter's syndrome, can be worsened by the co-existence of one or more well-known thrombophilic conditions, as shown by the relatively young age of the patient. More studies are needed to clearly understand the pathogenesis of venous thromboembolism in males affected by Klinefelter's syndrome.

Severe Arterial Thrombophilia Associated With a Homozygous MTHFR Gene Mutation (A1298C) in a Young Man With Klinefelter Syndrome

“…6 The increased thrombotic risk in those patients can be partially explained with hypofibrinolysis due to androgen deficiency. Additional genetic or acquired thrombophilic states, including factor V Leiden mutation, 8 antiphospholipid antibody syndrome, 9 G20210A prothrombin mutation plus factor V Leiden mutation, 7 and increased activity of factor VIII coagulant 10 were detected in KS patients complicated with venous thrombosis in isolated cases. To our knowledge, arterial thrombotic events have not been reported yet in KS patients.…”

“…To our knowledge, only 4 patients with KS complicated with venous thrombosis were reported to have additional thrombophilic states in the English literature. [7][8][9][10] However, no data are present concerning an association between KS complicated with arterial thrombosis and well-known thrombophilic states. We herein present a young man with KS who developed acute arterial thrombosis during testosterone replacement therapy.…”

MANAGEMENT OF ENDOCRINE DISEASE: Klinefelter syndrome, cardiovascular system, and thromboembolic disease: review of literature and clinical perspectives

“…Twenty-three consecutive KS patients under testosterone replacement therapy have been included as a case group and 46 agematched healthy males recruited among hospital staff served as controls. We observed an increased platelet reactivity in KS (115); (v) deficit and inhibition of C and S proteins (116,117,118,119,120,121,122,123); (vi) high levels of homocysteine associated with antithrombin III (AT-III) alterations (124) or other; (vii) factor V Leiden alterations (125,126,127) (See Supplemental data 2 for details). It is worth mentioning the role of testosterone replacement therapy in hemostasis.…”

49, XXXXY Syndrome with Unilateral Renal Aplasia, Proteinuria, and Venous Thromboembolism

“…We excluded inherited risk factors for venous thrombosis, such as antithrombin III deficiency, protein C deficiency, protein S deficiency, factor V Leiden, and prothrombin G20210A. Among them, factor V Leiden and prothrombin G20210A have been reported in a Klinefelter patient with venous thromboembolism (21).…”