Background: In Klippel-Trenaunay syndrome (KTS), a
congenital combined vascular (capillary, venous and
lymphatic) malformation with localised disturbed growth,
venous thromboembolisms (VTEs) are frequently reported
in small cohorts. Design and methods: We quantified the frequency of VTE by screening a large KTS-patient cohort with duplex compression ultrasonography. Additionally, we performed a case-control study to evaluate whether coagulation alterations were related to VTE and magnitude of vascular malformations as quantified by magnetic resonance imaging (MRI). Results: Twenty-nine (39%) of 75 patients had signs of current or previous VTE, including superficial venous thrombosis, six (8%) of whom had a deep venous thrombosis or a pulmonary embolism. Compared with 105 controls, 54 adult patients (both: median age 33 years) had higher plasma levels of D-dimer, medians 266 (IQR 195-366) versus 457 (IQR 270-3840) mg/l (p<0.001), respectively. They tended to have lower protein C (p=0.10) and free protein S (p=0.07) levels compared with controls. Compared with young-adult controls (n=62), KTS children (n=21) also had higher median D-dimer levels (p<0.001), and lower protein C (p=0.003) and protein S (p=0.01) levels. The extent of the vascular malformations on MRI was positively correlated with D-dimer plasma levels (r-spearman=0.329; p<0.05). Conclusions: Otherwise healthy KTS patients had a very high rate of current or previous VTE. Very high D-dimer levels were observed and these were related to the extent of the vascular malformation. Based on these findings we advise appropriate patient education on the signs and symptoms of thromboembolic complications in these patients, and screening for VTE in case of complaints.