Background
Klinefelter syndrome (KS) is the most common chromosomal aneuploidy in men, occurring in 1:600 males, 80-90% of whom have a 47,XXY karyotype. Clinical features vary but include androgen deficiency and infertility. Venous thromboembolism (VTE) is also increasingly recognised, with KS patients demonstrating both a higher risk of (hazard ratio [HR] 3.95), and higher mortality from (HR 1.76) thrombotic events (1).
Context
Clinical Andrology Service, Hudson Institute of Medical Research and Monash Health, Victoria.
Cases
Ten of the 88 (11.3%) KS patients reviewed in our clinic over a 10-year period (2011-2021) have had at least one VTE event. Median age at first VTE event was 40.4 years (range 20-54); four patients had recurrent VTE. 16 VTE events were recorded during this time; the most frequent were deep vein thrombosis (n = 8) and pulmonary embolism (n = 5), with one episode each of superficial lower limb thrombus, cerebral vein thrombus, and superior mesenteric vein thrombus. Androgen replacement at the time of VTE was depot intramuscular (n = 13) or transdermal (n = 3). Hb prior to VTE ranged from 145-183g/L, and haematocrit ranged from 0.41-0.52. Additional risk factors were overweight or obesity (n = 5) and smoking (n = 3). Inherited thrombophilia work-up was performed in eight patients, one patient with superficial thrombophlebitis was not investigated, and one patient was lost to follow-up. Of those who underwent investigation, Factor V Leiden heterozygosity was identified in two cases.
Conclusion
VTE is an important co-morbidity of KS, affecting over 10% of men seen in our clinic. Further research is required regarding the nature of coagulation abnormalities that contribute to greater VTE risk in KS patients, approaches to alleviate this risk, and the role of VTE prophylaxis amongst the KS cohort.