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Mechanical prophylaxis for travellers’ thrombosis: a comparison of three interventions that promote venous outflow

2007; Elsevier BV; Volume: 5; Issue: 7 Linguagem: Inglês

10.1111/j.1538-7836.2007.02584.x

1538-7933

Michiel Coppens, A.J.M. Schreijer, Ferco H. Berger, Suzanne C. Cannegieter, Frits R. Rosendaal, Harry R. Büller,

Travel-related health issues

The association between long‐haul travel and venous thromboembolism (VTE) has been well established and the absolute risk of clinically manifest VTE after air travel is estimated at one per 4500 travellers for flights lasting more than 4 h [1Cannegieter S.C. Doggen C.J. Van Houwelingen H.C. Rosendaal F.R. Travel‐related venous thrombosis: results from a large population‐based case control study (MEGA Study).PLoS Med. 2006; 3: e307Crossref PubMed Scopus (161) Google Scholar, 2Kuipers S. Schreijer A.J. Cannegieter S.C. Middeldorp S. Buller H.R. Rosendaal F.R. The absolute risk of venous thrombosis after air travel (WRIGHT study).J Thromb Haemost. 2005; 3: P1657Google Scholar]. This risk is further increased in individuals with additional risk factors, such as inherited thrombophilia, oral contraceptive use, obesity, and tall or short stature [1Cannegieter S.C. Doggen C.J. Van Houwelingen H.C. Rosendaal F.R. Travel‐related venous thrombosis: results from a large population‐based case control study (MEGA Study).PLoS Med. 2006; 3: e307Crossref PubMed Scopus (161) Google Scholar, 3Martinelli I. Taioli E. Battaglioli T. Podda G.M. Passamonti S.M. Pedotti P. Mannucci P.M. Risk of venous thromboembolism after air travel: interaction with thrombophilia and oral contraceptives.Arch Intern Med. 2003; 163: 2771-4Crossref PubMed Scopus (145) Google Scholar]. The next question is how to adequately prevent this disease. Prerequisites for any preventive measure for travellers' thrombosis are that they are effective, safe and easily applicable in large groups of otherwise healthy travellers. The preventive effect of aspirin on venous thrombosis is small at best in most trials, and at the cost of a small, yet significantly increased risk of major bleeding [4Geerts W.H. Pineo G.F. Heit J.A. Bergqvist D. Lassen M.R. Colwell C.W. Ray J.G. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest. 2004; 126: 338S-400SAbstract Full Text Full Text PDF PubMed Scopus (2880) Google Scholar]. Low‐molecular weight heparins are effective, but are also likely to lead to an increase in major bleeding [4Geerts W.H. Pineo G.F. Heit J.A. Bergqvist D. Lassen M.R. Colwell C.W. Ray J.G. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest. 2004; 126: 338S-400SAbstract Full Text Full Text PDF PubMed Scopus (2880) Google Scholar]. In contrast, mechanical thrombosis prophylaxis, such as intermittent pneumatic compression devices, venous foot pumps or graduated compression stockings, are attractive in that they will not increase the risk of bleeding, but they have been studied less intensely than anticoagulants [4Geerts W.H. Pineo G.F. Heit J.A. Bergqvist D. Lassen M.R. Colwell C.W. Ray J.G. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest. 2004; 126: 338S-400SAbstract Full Text Full Text PDF PubMed Scopus (2880) Google Scholar]. It has been suggested that intermittent compression may lead to increased fibrinolytic activity through endothelial stimulation, which may contribute to the antithrombotic effect [5Chen A.H. Frangos S.G. Kilaru S. Sumpio B.E. Intermittent pneumatic compression devices – physiological mechanisms of action.Eur J Vasc Endovasc Surg. 2001; 21: 383-92Abstract Full Text PDF PubMed Scopus (146) Google Scholar]. We earlier showed that intermittent mechanical compression (IMC), exerted by a small device designed especially for prevention of travellers' thrombosis, improved venous outflow in healthy volunteers [6Coppens M. Van Doormaal F.F. Schreijer A.J. Rosendaal F.R. Buller H.R. Intermittent mechanical compression for prevention of travellers' thrombosis.J Thromb Haemost. 2006; 4: 1836-8Crossref PubMed Scopus (3) Google Scholar]. The present cross‐over study compared the effect of IMC with that of graduated compression stockings and periodical exercise in six volunteers, over 55 years of age, none of whom had a history of VTE or heart failure (three men, mean body mass index 28 kg m−2, range 23–33). IMC was exerted using a lightweight device (AviaFit™; FlowMedic Ltd, Caesarea, Israel), placed on both calves with a 10‐cm‐wide strap, generating 1 pulse min−1 with a pressure of 45 mmHg during 7 s. Standard below‐the‐knee graduated compression stockings were used with a pressure of 25–35 mmHg (Luxovar Prestige; Varitex, Haarlem, the Netherlands). Periodic exercise consisted of a 4‐min exercise DVD, used by a commercial airline on long flights. Hourly exercises involved circular movements of the arm, shoulders and ankles, as well as knee lifting from an upright position. Volunteers were exposed to 8 h of strict seated immobilization, with standardized eating and drinking conditions and two lavatory interruptions. All volunteers were exposed to each intervention in a random order on three different test days, 2 weeks apart. Effects of the interventions were assessed by measurement of popliteal vein flow velocity, changes in lower extremity volume and by overall fibrinolytic activity. All measurements were performed, and blood samples taken, shortly before the start, and at the end of the 8 h seated immobilization. An additional flow velocity measurement was taken halfway through the experiment. Both peak flow velocity and mean flow velocity over a 15‐s interval were measured using duplex ultrasonography. Mean flow measurements in volunteers with IMC were taken in between two compressions; measurements in volunteers with periodical exercise were taken just before the hourly exercises. An increase in lower extremity volume was calculated by measuring the volume just before and after immobilization at 30 cm from the ground using a water bath. Global fibrinolytic capacity (GFC), as described by Giddings et al. [7Giddings J.C. Morris R.J. Ralis H.M. Jennings G.M. Davies D.A. Woodcock J.P. Systemic haemostasis after intermittent pneumatic compression. Clues for the investigation of DVT prophylaxis and travellers thrombosis.Clin Lab Haematol. 2004; 26: 269-73Crossref PubMed Scopus (31) Google Scholar], was determined as a marker of overall activity and a relative increase after 8 h was calculated. At the beginning of the test days, the median of the mean popliteal vein flow velocity was 4.0 cm s−1 (range 1.8–8.1). The mean flow after 4 and 8 h of seated immobilization was not different and did not show an effect of any of the interventions (Table 1). Periodical exercise led to increased flow from 3.3 to 4.2 cm s−1, measured immediately before and 2–10 min after the exercises, but this effect did not last. Contraction of the IMC device induced a flow pulse with a median peak velocity of 43.7 cm s−1, which was higher than median peak flow velocities induced by compression stockings (8.7 cm s−1) or periodical exercise (13.3 cm s−1, Table 1). Compression stockings resulted in a slight decrease in lower extremity volume (3 mL), whereas volunteers with IMC and periodical exercise experienced a median volume increase of 37 and 47 mL, respectively (Table 1). GFC was increased after 8 h as compared with baseline with all interventions, and this increase was highest after periodical exercise (Table 1).Table 1Effects of intermittent mechanical compression (IMC), periodical exercise and compression stockings on venous flow, lower extremity volume and fibrinolysis during 8 h of seated immobilizationVolume increase (mL)Relative GFC increase (ratio)Peak flow velocity (cm s−1)Mean flow velocity (cm s−1)IMC37 (−30; 260)2.3 (1.4; 3.7)43.7 (30.2; 52.6)*T03.9 (1.8; 4.6)T42.9 (2.1; 6.4)T83.7 (2.5; 5.9)Periodical exercise47 (−37; 75)3.5 (1.9; 114.5)13.3 (6.6; 14.0)T03.9 (3.1; 8.1)T43.3 (1.2; 3.8)T83.7 (2.6; 5.0)Compression stockings−3 (−50; 58)2.5 (0.9; 4.6)8.7 (7.7; 19.6)T04.2 (1.9; 5.2)T43.8 (3.0; 8.0)T83.5 (2.6; 4.0)All values expressed as median and (range). *P = 0.02, compared with periodical exercise and compression stockings (Mann–Whitney U‐test); all other inter‐group differences were not statistically significant. GFC: global fibrinolytic capacity; T0: baseline; T4: 4 h; T8: 8 h. Open table in a new tab All values expressed as median and (range). *P = 0.02, compared with periodical exercise and compression stockings (Mann–Whitney U‐test); all other inter‐group differences were not statistically significant. GFC: global fibrinolytic capacity; T0: baseline; T4: 4 h; T8: 8 h. This study compared the potential effect of IMC, graduated compression stockings and periodical exercise on venous flow, lower extremity volume and fibrinolysis. The findings indicate that IMC induces flow pulses once per minute with a peak flow velocity that is unmatched by either compression stockings or periodical exercise. Although the mean flow velocity in the popliteal vein immediately after exercise was briefly increased, none of the interventions demonstrated a lasting effect. Lower extremity volume measurement after immobilization suggested a beneficial effect of the compression stockings, although the range of individual measurements was rather large. Finally, GFC was increased after 8 h of immobilization, but from these data we can not determine whether this increase was caused by the interventions or by circadian variation of fibrinolytic activity. The increase in GFC was somewhat more pronounced after periodical exercise. We assumed that the mechanisms by which mechanical thrombosis prophylaxis may prevent venous thrombosis are a reduction of edema, increase of venous return, activation of fibrinolysis, or a combination hereof. Our findings suggest that each of the tested interventions seems to improve a different aspect, while none of the interventions are able to improve all three. All interventions have the major advantage that they do not increase the risk of bleeding and are fairly easily applied in large groups of individuals. Which intervention is superior in the setting of prevention of air travel‐related venous thrombosis will have to be clinically evaluated. The authors state that they have no conflict of interest. The intermittent mechanical compression devices and compression stockings were kindly supplied by the manufacturers (FlowMedic Ltd. and Varitex, respectively).