From the Research
Patients with Klinefelter syndrome have an increased risk of thrombosis and should be monitored closely, especially when starting testosterone replacement therapy, with consideration of anticoagulation therapy and lifestyle modifications to reduce this risk. The increased risk of thrombosis in Klinefelter syndrome is likely related to the chromosomal abnormality (47,XXY) causing hormonal imbalances, with elevated estrogen levels promoting hypercoagulability, and potential platelet dysfunction and endothelial abnormalities contributing to the prothrombotic state 1. For prevention, lifestyle modifications including:
- Maintaining healthy weight
- Regular exercise
- Avoiding prolonged immobility
- Not smoking are essential. When thrombosis occurs in Klinefelter patients, standard anticoagulation therapy is recommended, typically starting with low molecular weight heparin (such as enoxaparin 1mg/kg twice daily) followed by oral anticoagulants like warfarin (target INR 2-3) or direct oral anticoagulants (DOACs) such as rivaroxaban 15mg twice daily for 21 days, then 20mg daily 2. Treatment duration is typically 3-6 months for provoked thrombosis and may be longer or indefinite for unprovoked events. Testosterone therapy should be carefully managed in these patients, with consideration of transdermal formulations (50-100mg daily) which may carry lower thrombotic risk than injectable forms. The procoagulant imbalance in Klinefelter syndrome is expressed by increased thrombin generation both in platelet-poor plasma and platelet-rich plasma, which is at least in part explained by increased factor VIII levels 1. Further investigation on the benefit/risk ratio of antithrombotic prophylaxis is warranted. In patients with recurrent venous thromboembolism, fondaparinux is effective as daily injections and may be an alternative to standard therapies 3. Guidelines recommend the use of low molecular weight heparins for 6 to 14 days but advise against extended-duration thromboprophylaxis after hospital discharge 4.