Hemodynamic impairment, venous segmental disease, and clinical severity scoring in limbs with Klippel-Trenaunay syndrome

Background: Klippel-Trenaunay syndrome (KTS) is a complex congenital anomaly featuring two or more of the following: (1) capillary malformations (port-wine stains), (2) soft tissue or bony hypertrophy (or both), and (3) varicose veins or venous malformations. With the purpose of determining the actual significance of venous impairment in patients with KTS, we quantified the venous valvular competency and calf muscle pump function and examined their effect on clinical severity. Methods: Included were patients with near-normal function of affected limb(s) and minimal/small foot hypertrophy. Excluded were those with deep venous hypoplasia, aplasia or thrombosis, lymphedema, limb length discrepancy (>2.5 cm), peripheral arterial (ankle-brachial index <1.0), or cardiac disease and walking impairment. Venous duplex scanning, ascending venography, magnetic resonance imaging, strain gauge plethysmography, and a bone scanogram were performed. We studied eight men and seven women aged 15 to 51 years (median, 24 years). The KTS involved 17 limbs (unilateral in 13 patients and bilateral in 2). Contralateral limbs in patients with unilateral KTS acted as controls (n = 13). Venous clinical severity was graded according to the CEAP and venous clinical severity score (VCSS), and reflux complexity was classified according to the venous segmental disease score. Outflow obstruction (outflow fraction at 1 and 4 seconds; OF₁ and OF₄, respectively), reflux (venous filling index), calf muscle pump function (ejection fraction), and hypertension (residual volume fraction) were determined in both limbs with strain gauge plethysmography. Data, reported as median and interquartile range, were analyzed with the Mann-Whitney test. Results: Varicose veins or venous malformations occurred in the medial, posterior, or anterolateral limb segments of the ankle (7/17, 7/17, and 9/17), calf (10/17, 8/17, and 12/17), knee (9/17, 8/17, and 8/17), and thigh (10/17, 6/17, and 8/17, respectively). Venous malformations occupied the subcutaneous space (17/17) and extended into the subfascial space in 6 (35.3%) of 17 limbs. Abnormal reflux (>0.5 seconds) was distributed in the great (64.7%; 11/17) and small (5.9%; 1/17) saphenous veins and the common femoral (23.5%; 4/17), femoral (41.1%; 7/17), popliteal (29.4%; 5/17), perforator (70.6%; 12/17), and axial calf (35.3%; 6/17) veins. There was no difference in the OF₁ and OF₄ between the affected limbs and the controls. Limbs with KTS had a fivefold greater venous filling index (0.133-0.46 mL · 100 mL^-1 · s^-1; 0.258 mL · 100 mL^-1 · s^-1) than the controls (0.034-0.055 mL · 100 mL^-1 · s^-1; 0.046 mL · 100 mL^-1 · s^-1; P < .0001), and this was linked to a higher venous segmental disease score (3 [2-4] vs 0 [0-1]; P < .0001). Limbs with KTS had half the ejection fraction (20.8%; 12.3%-24%) of the controls (39.3%; 30.9%-64.6%) and twice as high a residual venous fraction (77% [69.6%-84.5%] vs 40.9% [20.6%-60%]; both P < .004). Patients complained of swelling (100%; 15/15), aching (100%; 15/15), pain (93.3%; 14/15) and heaviness (100%; 15/15), tiredness (66.7%; 10/15), and tightness (33.3%; 5/15) of the limb(s) with KTS. Limbs with KTS had a worse (1) venous clinical severity by 11 VCSS points (11 [8-12] vs 0 [0-1]) and (2) clinical status by 3 CEAP classes (C3 [C3-C4] vs C0 [C0-C2]) than the control limbs (both P < .0001). Conclusions: Venous disease in limbs with KTS is a major source of morbidity in affected patients. Limbs with KTS are characterized by complex reflux patterns, severe valvular incompetence, calf muscle pump impairment, and venous hypertension, thus explaining the advanced clinical severity (VCSS) and CEAP grade.