Cindy Towns is an consultant in Internal Medicine and Geriatrics. She is an adjunct senior lecturer and a senior clinical lecturer at the University of Otago. This case was co-authored by Olivia Carleton (house surgeon) and Frances Mein-Smith (registrar) who unfortunately were not able to attend to present
A Rare Provocation: A Case Of Extensive Pulmonary Embolism In A Man With Previously Undiagnosed Klinefelter Syndrome
A 50 year-old man was referred to hospital with 36 hours of breathlessness and pleuritic chest pain. He took no medications and had no significant medical history. He had no known risk factors for pulmonary embolism (PE).
On examination, he was noted to be tall and obese. He was hypotensive (100/80mmHg) with an elevated JVP but no oedema; his chest was clear to auscultation. Bilateral gynaecomastia and sparse facial hair were observed and subsequent testicular exam revealed bilateral small volume testicles.
He was hypoxic, requiring 4 litres of oxygen to maintain 92% oxygen saturation. Troponin T and BNP were raised and his ECG showed anterior and inferior T-wave inversion. Bedside echocardiogram demonstrated septal bowing. Extensive PE was confirmed with computed tomography pulmonary angiogram. He was commenced on anticoagulants. Reproductive axis testing revealed low testosterone, raised lutenising hormone and raised follicle stimulating hormone. Karyotype testing (47 XXY) confirmed Klinefelter Syndrome (KS).
KS is an underdiagnosed chromosomal disorder males and the likely sole provoking factor in this presentation. Although not well understoon, it is postulated that low levels of androgen result in an increase of plasminogen activator inhibitor-1and therefore hypofibrinolysis1, 2. Vascular abnormalities and platelet hyper-aggregability may also play a role (1). A recent prospective cohort study appears to confirm the risk3.
Mutations in known thrombophilia genes have been reported in KS patients but this man did not have thrombophilia testing prior to treatment1, 2, 4. Testosterone replacement also increases the risk for PE but our patient was undiagnosed and therefore untreated at initial presentation3, 4.
KS confers a significant additional risk for VTE and should be treated similarly to other risk factors in terms of prevention and management.
Glueck, C.J., Jetty, V., Goldenberg, N., Shah, P. & Wang, P. (2017). Thrombophilia in Klinefelter syndrome with deep venous thrombosis, pulmonary embolism, and mesenteric artery thrombosis on testosterone therapy: A pilot study. Clinical and Applied Thrombosis/Hemostasis, 23 (8), 973-9.
Glueck, C.J. & Wang P. (2014). Testosterone therapy, thrombosis, thrombophilia, cardiovascular events. Metabolism, 63 (8), 989-94.
Zöller, B., Ji. J., Sundquist, J. & Sundquist, K. (2016). High risk of venous thromboembolism in Klinefelter syndrome. Journal of the American Heart Association, 20 (5), e00356.
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. (2009). Internal Medicine, 48 (18), 1681-5.