Klippel Trenaunay Weber syndrome

Klippel-Trenaunay-Weber syndrome (KTWS) is a rare, congenital disorder characterized by the triad of varicose veins, cutaneous hemangiomas, and hypertrophy of soft tissue and bone. We present the case of a woman with KTWS, cdr pulmonale, and death due to recurrent pulmonary embolism (PE). The risk of deep venous thrombosis and PE in patients with KTWS is evaluated, and treatment recommendations are made with emphasis on the role of early, aggressive management in the subset of patients with KTWS known to have thromboembolic disease. (CHEST 1999; 115:1199-1201)

Key words: Klippel-Trenaunay-Weber syndrome; pulmonary embolism; deep venous thrombosis

Abbreviations: DVT = deep venous thrombosis; INR = international normalized ratio; KTWS = Klippel-Trenaunay-Weber syndrome; PE = pulmonary embolism

Klippel and Trenaunay first described the syndrome of varicose veins, cutaneous hemangiomas, and hypertrophy of soft tissue and bones in 1900.[1] To date, there are less than 1,000 reported cases of Klippel-Trenaunay-Weber syndrome (KTWS). We report our experience with a woman with KTWS who had recurrent pulmonary embolism (PE) leading to her death. This case report will help increase recognition of the clinical manifestations of KTWS and suggests a more aggressive approach to associated thromboembolic disease.

CASE REPORT

A 48-year-old woman with KTWS was referred to a university hospital with a history of increasing shortness of breath over 2 months, jugular venous distention, and lower extremity edema. On examination, she had a BP of 110/80 mm Hg, a pulse of 108 beats/Din, and a respiratory rate of 20 breaths/min. Her lungs were clear to auscultation. Cardiac examination revealed widely split second heart sounds and a prominent pulmonic valve closure. The lower extremities were both edematous, the right more affected than the left, with palpable cords and varicosities covering the entire extremity. Multiple areas of grouped hemangiomas were seen on the posterior hand, dorsal right foot, upper mid back, and the right labia majora. The remainder of the examination was normal. Initial evaluation included a chest CT scan revealing pulmonary artery enlargement (Fig 1), a ventilation-perfusion scan that revealed multiple unmatched perfusion defects, and an echocardiogram. The echocardiogram was significant for right atrial enlargement (58 mm), a fractional shortening of 37%, 3+ tricuspid valve regurgitation, 2+ pulmonic valve regurgitation, and a dilated inferior vend cava without collapse. Right ventricular peak pressure was estimated by echocardiogram to be 64 mm Hg. A Doppler ultrasound of the lower extremities was normal except for multiple varicosities in the distal right lower extremity. The patient refused further evaluation. A presumptive diagnosis of recurrent PE with secondary pulmonary hypertension prompted initiation of heparin. She was started on warfarin and a diuretic and discharged from the hospital. After an initial adjustment period, her international normalized ratio (INR) remained between 2.2 and 3.9 on periodic outpatient visits.

[Figure 1 ILLUSTRATION OMITTED]

Ten months after her initial hospitalization, she was readmitted for decompensated right heart failure. Her INR at admission was 2.31. A repeat ventilation-perfusion senn showed new perfusion defects in the anterior and posterior segments of the right upper lobe. Heparin was administered and warfarin was continued. A pulmonary angiogram demonstrated distal pruning of the pulmonary arterioles bilaterally and a pulmonary artery pressure of 94/42 mm Hg. Because the patient had new PEs adequate anticoagulation, an inferior vend cava filter was placed. She was maintained on warfarin and her INR ranged between 2.3 and 4.1.

On the eighth hospital day the patient became acutely dyspneic. She was cyanotic and hypotensive with a systolic BP of 78 mm Hg. A blood gas revealed a pH of 7.09, a Pa[CO.sub.2] of 51 mm Hg, and a Pa[O.sub.2] of 24 mm Hg. The patient was transferred emergently to the ICU where she remained hypoxemic and hypotensive despite ventilatory support, pressor agents, and thrombolytics, and she subsequently died.

RESULTS OF AUTOPSY

The pathologic cause of death was cor pulmonale secondary to PE. Internal examination revealed right ventricular hypertrophy of the heart and congested lungs. Microscopically, a thickened pulmonary interstitium was noted, with areas of alveolar hemorrhage, edema, and hemosiderin-laden macrophages. The pulmonary arterioles showed hypertrophied muscular layers with numerous thrombi of different ages, ranging from recent to remote with complete organization of some vessels. Trichrome stains of the lung confirmed the presence of recanalization and the absence of plexiform lesions (Fig 2).

[Figure 2 ILLUSTRATION OMITTED]

DISCUSSION

The etiology of KTWS is unknown. Manifestations of the syndrome begin at birth or shortly after, with most patients displaying cutaneous hemangiomas of the portwine type. As children begin to walk, varicosities become more obvious. The varicosities tend to be located along the lateral aspect of a lower limb and medially at the groin.[1] Chronic venous insufficiency develops in the second and third decades with associated venous stasis ulcers, recurrent thrombophlebitis, and cellulitis. Limb and soft tissue hypertrophy usually manifests several years later and involves a single lower extremity. Rarely, one entire side of the body is involved producing hemihypertrophy.

The pulmonary abnormalities associated with this syndrome include pulmonary vein varicosities,[2] pulmonary lymphatic obstruction,[3] cavernous hemangiomas of the pleura leading to hemothorax,[1] and thromboembolic phenomena[4-6] Pulmonary varicose veins are apparently rare as judged by the small number of reported cases.[3] Smooth muscle hyperplasia leads to plexiform lymphatic lesions and ultimately obstruction.

Thromboembolic events are relatively common among patients with KTWS. Baskerville et al[7] reported a 17% incidence of radiographically demonstrated deep venous thrombosis (DVT) in a series of 49 patients with KTWS seen at one institution. In comparison, the incidence of autopsy-proven DVT in nonhospitalized patients is estimated to be 5%.[8] In the same study by Baskerville et al, there was a 10-fold increase in the incidence of postoperative thromboembolism in patients with KTWS compared with other surgical patients.

The most acceptable explanation for a higher incidence of DVT in this patient population has been the abnormalities in the venous system. However, Baskerville and colleagues, using plethysmography, could not differentiate the venous anatomic abnormalities of patients with KTWS with DVT or PE from those patients without DVT or PE.[6] The same study did demonstrate that fibrinopeptide A was markedly elevated and thrombin activity was abnormal in KTWS patients with thromboembolic disease, suggesting a procoagulant state as an etiology for the high incidence of DVT. This study, however, was uncontrolled and retrospective.

We have noticed that, despite a higher incidence of DVT in patients with KTWS, PE appears to be a seldom-recognized complication of this syndrome. In an extensively studied small group of patients with KTWS, Baskerville and associates[7] estimated the incidence of PE in patients with KTWS to be 14% to 22%. Although approximately 1,000 cases of KTWS have been reported to date, only 10 cases of PE in patients with KTWS have been published.[4-7,9] Of the 10 reported cases, PE was recurrent in three patients, leading to pulmonary hypertension and subsequent death.[4,5] One of the patients was similar to our own, experiencing recurrent DVT and PE despite adequate anticoagulation.[5]

For lack of large experience there are no established treatment regimens for thromboembolic phenomena in patients with KTWS. It appears reasonable, based on the significant incidence of venous thromboembolism in this patient population, to recommend avoidance of estrogen use and provision of aggressive DVT prophylaxis in patients undergoing surgical procedures. Based on the poor outcome of our patient and four others described in the literature,[4,5,9] we suggest aggressive treatment of thromboembolic disease, including anticoagulation with warfarin to a goal INR between 3 and 4, and early placement of an inferior vena caval filter. We recommend venographic evaluation of the pelvic and abdominal venous anatomy in order to assess for significant collateral venous circulation, which may warrant suprarenal filter placement. For this reason, currently accepted noninvasive studies used in the evaluation of patients with suspected DVT are probably inadequate in this patient group.

In summary, KTWS is a rare cause of DVT and PE and should be considered when the characteristic historical and physical findings are present. Awareness of this syndrome and knowledge of its clinical implications are important for appropriate management.

ACKNOWLEDGMENTS: We thank Karen Adams, MA, for her assistance and expert advice and Susan Murin, MD, for her thoughtful review.

REFERENCES

[1] You CK, Rees J, Gillis DA, et al. Klippel-Trenaunay syndrome: a review. Can J Surg 1983; 26:399-403

[2] Owens DW, Garcia E, Pierce RR, et al. Klippel-Trenaunay-Weber syndrome with pulmonary vein varicosity. Arch Dermatol 1973; 108:111-113

[3] Joshi M, Cole S, Knibbs D, et al. Pulmonary abnormalities in Klippel-Trenaunay syndrome. Chest 1992; 102:1274-1277

[4] Muluk SC, Ginns LC, Semigran M J, et al. Klippel-Trenaunay syndrome with multiple pulmonary emboli: an unusual cause of progressive pulmonary dysfunction. J Vasc Surg 1995; 21:686-690

[5] Mikula N, Gupta SM, Miller M, et al. Klippel-Trenaunay-Weber syndrome with recurrent pulmonary embolism. Clin Nucl Med 1991; 16:253-255

[6] Baskerville PA. Maladie thrombo-embolique et anomalies veineuses congenitales. Phlebologie 1987; 40:531-536

[7] Baskerville PA, Ackroyd JS, Thomas ML, et al. The Klippel-Trenaunay syndrome: clinical, radiological and haemodynamic features and management. Br J Surg 1985; 72:232236

[8] Nordstrom M, Lindblad B. Autopsy verified venous thromboembolism within a defined urban population: the city of Malmo, Sweden. APMIS 1998; 106:378-384

[9] Jacob AG, Driscoll DJ, Shaughnessy WJ, et al. Klippel-Trenaunay syndrome: spectrum and management. Mayo Clin Proc 1998; 73:28-36

(*) From the Division of Pulmonary and Critical Care Medicine (Drs. Gianlupi, Harper, and Marelieh), Department of Internal Medicine, and the Department of Pathology (Dr. Dwyre), University of California, Davis Medical Center, Sacramento, CA.

Manuscript received July 1, 1998; revision accepted October 29, 1998.

Correspondence to: Gregory P. Marelich, MD, FCCP, Division of Pulmonary and Critical Care Medicine, University of California-Davis Medical Center, 4150 V Street, Suite 3400, Sacramento, CA 95817; e-mail: gpmarelich@ucdavis.edu

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