The aim of this study was to evaluate the development of edema, and superficial and deep vein thrombosis (DVT) prophylaxis with an oral profibrinolytic agent (Flite Tabs, 150 mg pinokinase, Aidan, Tempe, AZ, USA) in long-haul flights (7-8 hours), in high-risk subjects. A group of 300 subjects was included; 76 were excluded for several problems including concomitant treat ments ; 204 were randomized into 2 groups (active treatment or placebo) to evaluate the effects of prophylaxis with Flite Tabs. An exercise program was used in both groups. The femoral, popliteal, tibial, and superficial veins were scanned with ultrasound before and within 90 minutes after flights. Of the included subjects, 92 of 103 controls and 94 of 101 treated subjects completed the study. Dropouts were due to connection problems. Age, gender, and risk distribution were comparable in the groups. In the treatment group, no DVT was observed. In the control group, 5 subjects (5.4%) had a DVT and there were 2 superficial thromboses (7 events in 92 subjects; 7.6%). At inclusion, edema was comparable in the 2 groups. After flights there was an increase in score in controls (+12%) in comparison with a decrease (-15%) in the Flite Tabs group (the difference in variation was statistically significant). Intention-to-treat analysis for thrombotic events shows 18 failures in controls (11 lost to follow-up + 7 throm botic events) of 92 subjects (19.6%) in comparison with 7 failures (of 94 subjects, equivalent to 7.4%) in the treatment group (p<0.05). Events were asymptomatic. In conclusion, Flite Tabs were effective in reducing thrombotic events and in controlling edema in high-risk subjects in long flights.
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References
1.
Geroulakos G. , Hossain J., Tran T.: Economy-class syndrome presenting as phlegmasia caerulea dolens. Eur J Vasc Endovasc Surg20:102-104, 2000.
2.
Perry K.: Blood clot kills woman after flight. Guardian2001; 23 Oct.
3.
Homans J.: Thrombosis of the deep leg veins due to prolonged sitting. N Engl J Med250:148-149, 1954.
4.
Symington IS , Stack BHR: Pulmonary thromboembolism after travel. Br J Chest17:138-140, 1977.
5.
Simpson K.: Shelter deaths from pulmonary embolism. Lancet 11:744, 1940.
6.
Ferrari E., Chevallier T., Chapelier A., et al : Travel as a risk factor for venous thromboembolic disease: A case control study. Chest115:440-444, 1999.
7.
Cruickshank JM , Gorlin R., Jennett B.: Air travel and thrombotic episodes: The economy class syndrome. Lancet 2:497-498, 1988.
8.
Kraaijenhagen R., Haverkamp D., Koopman Mmw, et al: Travel and risk of venous thrombosis . Lancet 356: 1492-1493, 2000 .
9.
Sarvesvaran R.: Sudden natural deaths associated with commercial air travel. Med Sci Law26:35-38, 1986.
10.
Landgraf H. , Vanselow B., Schulte-Huerman D., et al: Economy class syndrome: Rheology fluid balance and lower leg oedema during a simulated 12-hour long-distance flight. Aviat Space Envir Med65:930-935, 1994.
11.
AMA Commission on Emergency Services: Medical aspects of transportation aboard commercial aircraft. JAMA247:1007-1011, 1982.
12.
Gertler JP, Perry L., L'Italien G., et al : Ambient oxygen tension modulates endothelial fibrinolysis . J Vasc Surg18:939-946, 1993.
13.
Bendz B., Rostrup M., Sevre K., et al: Association between acute hypobaric hypoxia and activation of coagulation in human beings. Lancet 356:1657-1658, 2000.
14.
Belcaro G., Geroulakos G., Nicolaides AN, et al : Maladie veineuse thrombo-embolique apres vol aerien. Les etudes LONFLIT. Angeiologie53:17-21, 2001.
15.
Belcaro G., Geroulakos G., Nicolaides AN, et al : Venous thromboembolism from air travel. The Lonflit Study. Angiology52:369-374, 2001.
16.
Cesarone MR, Belcaro G., Nicolaides AN, et al : Venous thromboembolism from air travel: The Lonflit3 study. Prevention with aspirin vs low-molecular weight-heparin (LMWH) in high-risk subjects: A randomised trial. Angiology53:1-6, 2002.
17.
Belcaro G.: Venous thrombosis and air-travel: Prevention with aspirin or low-molecular-weight-heparin . Circulation104:II-528, 2001 .
18.
Belcaro G., Geroulakos G., Nicolaides AN, et al : Prevention of deep venous thrombosis on long-haul flights . J Am Coll Cardiol39(suppl 5):212A, 2002.
19.
Anonymous: Stockings, heparin found to eliminate "coach class" syndrome. Am Heart Assoc Sci Sessions3:8, 2001.
20.
Fujii M., Ito Y., Ko K., et al: Fibrinolytic activity of nattokinase. Nihon Kessen Shiketsu Shi43:1124, 1994.
21.
Sumi H., Hamada H., Nakanishi K., et al : Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acte Haematol84:139-141, 1990.
22.
Editorial.Le pycnogénol: Une substance douée de properiétés angioprotectrices dans le traitement de l'insuffisance veineuse chronique. J Suisse Med Globale1/95:69-73, 1995.
23.
Petrassi C. , Mastromarino A., Spartera C.: Pycnogenol® in chronic venous insufficiency . Phytomedicine7: 383-388, 2000.
24.
Belcaro G., Nicolaides AN, Stansby G.: The Venous Clinic. London: Imperial College Press, 1999.
25.
Belcaro G., Nicolaides AN: Noninvasive Investigations in Vascular Disease. London : Imperial College Press, 2001.
26.
Cesarone MR , Belcaro G., Geroulakos G., et al: Flight microangiopathy in medium-to-long distance flights: Prevention of edema and microcirculation alterations with HR (Paroven,Venoruton; 0-(beta-hydroxyethyl)-rutosides : A prospective-randomised, controlled trial. J Cardiovasc Pharmac Ther7(suppl I):S17-S20, 2002.
27.
Thulesius O. : Chronic venous insufficiency and varicose veins physiopathological view points. Lakartidningen80:1791-1801, 1983.
28.
Cesarone MR , Belcaro G., Nicolaides AN, et al: The edema tester in the evaluation of swollen limbs in venous and lymphatic disease. Panmin Med41:10-14, 1999.
29.
Belcaro G, Bollinger A, Hoffman U, et al (eds): Laser-Doppler . London: Med-Orion, 1995.
30.
Mendis S., Yach D., Alwan A.: Air travel and venous thromboembolism. Bull WHO80:403-406, 2002.
31.
Cesarone MR, Meli E.: Volare con Sicurezza. Jet-leg. Il problema dell'edema e della trombosi in voli di lunga durata. Turin, Italy: Ediz Minerva Medica, 2001.
32.
Scurr JH, Machin SJ, Bayley S., et al: Frequency and prevention of symptomless deep-vein thrombosis in long-haul flights: A randomised trial. Lancet 357:1485-1489, 2001.
33.
Belcaro G., Cesarone MR, Shah S., et al: Prevention of edema, flight microangiopathy and venous thrombosis in long flights with elastic stockings. A randomized trial: The LONFLIT 4 Concorde Edema-SSL Study. Angiology53:635-645, 2002.
34.
Rosendaal FR , Buller HR, Kesteven P., et al: Long haul flights and deep vein thrombosis: Who is at risk?Br J Haematol120:367, 2003.
35.
Campbell C. , Rayner CF: Guidelines on prevention of venous thromboembolism during long haul flights. Thorax58:91-92, 2003.
36.
Schwarz T., Langenberg K., Oettler W., et al: Deep vein and isolated calf muscle vein thrombosis following long-haul flights: Pilot study. Blood Coag Fibrinolysis13:755-757, 2002.
37.
Schobersberger W., Hauer B., Sumann G., et al: Traveler's thrombosis: Incidence, etiology, prevention. Wien Klin Wochenschr114(1-2):14-20, 2002.
38.
Schobersberger W., Schobersberger B., Mittermayr M., et al: Travel-induced thrombosis: An update. Wien Med Wochenschr152:445-449, 2002.
39.
Teruya T., Arfvidsson B., Eklof B.: Could prolonged air travel be casually associated with subclavian vein thrombosis . J Travel Med9:17-19, 2002.
40.
Arya R., Barnes JA, Hossain U., et al: Long-haul flights and deep vein thrombosis: A significant risk only when additional factors are also present. Br J Haematol116:653-654, 2002.
41.
Murphy JF: The folded deckchair position: The problem of long-haul flights. Ir Med J94:260, 2001.
42.
Cesarone MR , Belcaro G., Errichi BM, et al: The LONFLIT4-concorde deep venous thrombosis and edema study: Prevention with travel stockings . Angiology54:143-148, 2001.
43.
Cesarone MR , Belcaro G., Brandolini R., et al: The LONFLIT4-venoruton study: A randomized trial. Prophylaxis of flight-edema in venous patients . Angiology54:137-142, 2003.
44.
Lethagen S. : The connection of increased risk of thrombosis and long-haul flights is not proved. Lakartidningen98:4063, 2001.
45.
Collin J.: Deep-vein thrombosis in long-haul flights. Lancet358:838, 2001.
46.
Reynolds M. : Deep-vein thrombosis in long-haul flights . Lancet358:838-839, 2001.
47.
Anderson R. : Deep-vein thrombosis in long-haul flights . Lancet358:837, 2001.
48.
Burnand KG, McGuinness CL, Smith A.: Deep-vein thrombosis in long-haul flights. Lancet358:837, 2001.
Teenan RP, McKay AJ: Peripheral arterial thrombosis related to commercial airline flights: Another manifestation of the economy class syndrome. Br J Clin Pract46:165-166, 1992.
51.
Hosoi Y., Geroulakos G., Belcaro G., et al: Characteristics of deep vein thrombosis associated with prolonged travel. Eur J Vasc Endovasc Surg24:235-238, 2002.
52.
Belcaro G., Cesarone MR, Nicolaides AN, et al : Prevention of flight venous thrombosis in high risk subjects with stockings or one-dose enoxaparine. Circulation106:II:721, 2002.
53.
Belcaro G., Cesarone MR, Nicolaides AN, et al : Prevention of venous thrombosis with elastic compression stockings during long-haul flights: The LONFLIT 5 JAP study. Clin Appl Thromb Hemost, in press.
54.
Jacobson B. , Munster M., Smith A., et al: The BEST study. A prospective study to determine business versus economy class syndrome as a cause of thrombosis . South Afr Med J, in press.
55.
Nicolaides AN: Investigation of chronic venous insufficiency : A consensus statement. Circulation102: 126-163, 2000.
56.
Belcaro G., Nicolaides AN, Veller M.: Venous Disorders : A Manual of Diagnosis and Treatment. Cambridge: Saunders, 1996.
57.
Dalen JE, Hirsh J., Guyatt GH: Sixth ACCP consensus conference on antithrombotic therapy. Chest119:1, 2001.
58.
Prevention of Venous Thromboembolism. International Consensus Statement, 2002 ed. London: Med-Orion, 2002.
59.
Cesarone MR , Belcaro G., Di Renzo A., et al: The pilgrim syndrome. Epidemiology and investigations of long-travel pilgrimage-related thrombosis. Eur Venous Forum Web J1:1, 2003.
60.
Gabor M., Engi E., Sonkodi S.: Die Kapillarwandresistenz und ihre beeinflussung durch wasserlösliche flavonderivate bei spontan hypertonischen rat-ten. Phlebologie22:178-182, 1993.
61.
Schmidtke I. , Schoop W.: Le pycnogénol: Thérapeutique médicamenteuse de l'œdème statique. J Suisse Med Globale3/95:114-115, 1995.
62.
Sumi H.: Structure and fibrinolytic properties of nattokinase, basic and clinical aspects of Japanese traditional food natto. JTTAS1:49, 1994.
63.
Sumi H., Baba K., Kishimoto N.: Active enzyme, prourokinase of natto and the fibrinolytic activity . Nihon Shokukakoushi43:139-40, 1996.
64.
Sumi H., Hamada H., Tsushima H., et al:A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese natto; a typical and popular soybean food in the Japanese diet. Experientia43:1110-1112, 1987 .
65.
Sumi H., Taya H., Nakajima N., Hiratani H.: Structure and fibrinolytic properties of nattokinase. Fibrinolysis6:86-89, 1992.
