Stephan Moll, MD writes… Klippel-Trenaunay Syndrome (KTS) is a rare disorder people are born with. Some individuals with KTS develop blood clots in legs, arms or pelvis (deep vein thrombosis = DVT) or in the lung (pulmonary embolism = PE). Patients with KTS have abnormal growth (malformations) of blood vessels (see photographs) and excessive growth of the soft tissue and bone of a leg and/or arm. The cause of the disorder is poorly understood, but there is evidence that genetic mutations lead to overactivity of proteins involved in vessel formation [ref 1]. The malformations involve the very small vessels (capillaries), larger veins, and the lymphatics. KTS affects only one side of the body, typically the leg or the arm, sometimes both. It can also involve the trunk and face and inner organs. Often, the blood vessel malformations consist of purplish-reddish birthmarks on the skin (see photograph, left leg affected) . The symptoms and findings associated with the disorder vary between individuals. Chronic pain and swelling of leg and arm can be a problem. The swelling may lead to skin breakdown (ulcers). A patient support group for KTS exists with an informative website.
DVT and PE in Patients with Klippel-Trenaunay Syndrome
Superficial clots (superficial thrombophlebitis), as well as more dangerous DVT and PE are well known complications of KTS. Clots probably form because (a) blood flow in the abnormal vessels is slow and disturbed (stasis) and because clotting proteins are activated in these abnormal vessels (coagulation activation). Clots are not uncommon: (a) a study of 49 patients with KTS showed that 11 (22.5 %) had DVT and PE problems: namely, 7 had PE and 8 DVT [ref 2]; (b) a study of 47 children with KTS showed DVT or PE in 11 % and superficial thrombophlebitis in 53 % [ref 3]; and (c) a study of 68 patients reported a history of DVT or PE in 17 %, and of superficial thrombophlebitis in 48 % [ref 4].
The recurrence rate of blood clots and the best treatment are not known. Open questions are:
- Do patients need to be on long-term warfarin (coumadin®, Jantoven®) after they have had an episode of DVT or PE?
- Should they be treated with warfarin or low molecular weight heparin (Lovenox® – Enoxaparin, Fragmin® = Dalteparin, Innohep® = Tinzaparin, etc.)
- Would the new oral anticoagulants Pradaxa® (Dabigatran) or Xarelto® (Rivaroxaban) be good choices?
- Should an IVC filter be placed to prevent recurrences of PE?
- What is the risk of recurrence of DVT or PE during pregnancy and how should pregnant women with KTS be managed? [ref 5]
How are KTS patients best treated?
- Awareness, Prophylaxis: As quite a few patients with KTS develop superficial thrombophlebitis, DVT or PE, patients should know the symptoms and risk factors of blood clots, so that they recognize them quickly and seek medical attention quickly and rapidly get diagnosed and treated (check here). They also need good DVT prophylaxis in risk situations, such as at time of surgery and hospitalization. Women need to know about the risk of blood clots with birth control pills (check here) and pregnancy.
- Choice of blood thinners: A 2005 publication [ref 6] reviewed all published cases of PE in individuals with KTS (10 patients are listed in the analysis), summarizing that several patients had recurrent DVT or PE in spite of being on warfarin (Coumadin®, Jantoven®). The authors of the article, therefore, conclude that “if DVT or PE is diagnosed, then these patients should receive therapy with low molecular weight heparin”. However, it has not been studied whether low molecular weight heparin is more effective in preventing blood clots. At present, it appears fair to conclude, that there is some risk for recurrence of DVT and PE, even while the patient is on adequate doses of warfarin. However, because of a lack of studies, publications and extensive experience, there are no established and accepted guidelines on treatment. Individual decisions need to be made.
- IVC filters: It is not clear whether patients with KTS who have had a DVT and/or PE may benefit from having an IVC filter placed into the big vein in the abdomen, the IVC (inferior vena cava), so that clots that break off from a leg DVT get caught in the filter before reaching the lung. Since some patients have abnormal vessels bypassing the IVC, a filter may not be protective. Also, the IVC may be involved by KTS and may be tortuous and wider than usual, making it difficult to find a filter big enough to fit and stay in place. Once again, individual decisions need to be made.
- Risk for bleeding: Lastly, since abnormal veins may also be seen in the inner organs, such as the intestine, some patients with KTS have an increased risk for bleeding. This also needs to be taken into consideration when considering long-term blood thinner.
- Tian XL et al: Identification of an angiogenic factor that when mutated causes susceptibility to Klippel-Trenaunay syndrome. Nature 2004;427:640-645.
- Baskerville PA et al: Thromboembolic disease and congenital venous abnormalities. Phlebologie 1987;40:531-536.
- Samuel M et al: Klippel-Trenaunay syndrome: clinical features, complications and management in children. Br J Surg 1995:82:757-761.
- Douma RA et al. Chronic pulmonary embolism in Klippel-Trenaunay syndrome. J Am Acad Dermatol 2012;66:71-7.
- Güngor Gündoğan T et al. Klippel-Trenaunay syndrome and pregnancy. Obstet Gynecol Int 2010:706850. Epub 2010 Dec 19.
- Hiras EE et al: Pulmonary thromboembolism associated with KTS. Pediatrics 2005;116:e596-e600.
Last updated: May 25th, 2012