The LONFLIT4--Concorde Deep Venous Thrombosis and Edema Study: prevention with travel stockings

BACKGROUND: The LONFLIT1+2 studies have established that in high risk subjects after long flights (> 10 hours) the incidence of deep venous thrombosis (DVT) is between 4% and 6%. The LONFLIT4 study was designed to evaluate the control of edema and DVT in low-medium risk subjects. The aim of this study was to evaluate edema and its control with specific stockings (ankle pressure between 20 and 30 mm Hg) in long-haul flights. The first part of the study included flights lasting 7-8 hours and the second part included flights lasting 11-12 hours. Ultrasound scans were used to assess thrombosis before and after the flights and a composite edema score was used to evaluate edema and swelling. A group of patients with microangiopathy associated to edema (diabetes, venous hypertension, anti-hypertensive treatment) were also included to evaluate the preventive effects of stockings during flight. Part I: DVT evaluation: Of the 74 subjects in the stocking group and 76 in the control group (150), 144 completed the study. Dropouts were due to low compliance or traveling and connection problems. Age and gender distribution were comparable in the 3 groups as was risk factor distribution. In this part of the study there were no DVTs. Edema Evaluation: The level of edema at inclusion was comparable in the two groups of subjects. After the flight there was an average score of 6.9 (1) in the control group. In the stocking group, the score was on average 2.3 (1), three times lower than in the control group (p < 0.05). Part II: DVT evaluation: Of the 66 included subjects in the stocking group and 68 in the control group (134), 132 completed the study. Dropouts were due to low compliance or connection problems. Age and gender distribution were comparable in the two groups. In the stocking group no DVT was observed. In the control group, 2 subjects had a popliteal DVT and 2 subjects had superficial venous thrombosis (SVT); in total 4 subjects (6%) in the control group had a thrombotic event; the incidence of DVT was 3%. The difference (p < 0.02) is significant. EDEMA EVALUATION: The composite edema score at inclusion was comparable in the two groups. After the flight there was a score of 7.94 (2) in the control group, while in the treatment group the score was 3.3 (1.2). MICROANGIOPATHY STUDY: In all these subjects, the level of edema was very high in the control group and significantly lower in the compression stocking group. Stockings are effective in controlling edema during flights even in subjects with microangiopathy and edema. Compression was well tolerated in normal subjects and in patients. CONCLUSION: The Kendall Travel Socks (Tyco Healthcare, Mansfield, MA, USA) which provide 20-30 mm Hg pressure at the ankle, are effective in controlling edema and reducing the incidence of DVT in both low-medium-risk subjects and in patients with microangiopathy and edema in long-haul flights (7-11 hours).     

The LONFLIT4-Concorde--Sigvaris Traveno Stockings in Long Flights (EcoTraS) Study: a randomized trial

The LONFLIT1/2 studies have established that in high-risk subjects after long ( > 10 hours) flights the incidence of deep venous thrombosis (DVT) may be between 4% and 6%. The LONFLIT4 study was aimed at evaluating the control of edema and DVT prevention in low-medium-risk subjects. In this study prophylaxis of edema with specific travel stockings was evaluated in 2 separate studies involving flights lasting 7 hours and 10-12 hours. Part I. Subjects at low-medium risk for DVT were contacted; 55 subjects were excluded for several nonmedical, travel-related problems or inconvenient evaluation time; the remaining 211 were randomized into 2 groups to evaluate prophylaxis with elastic stockings in 7-8-hour, long-haul flights. The control group had no prophylaxis; the treatment group used below-knee, Sigvaris Traveno elastic stockings (Ganzoni, Switzerland, producing 12-18 mm Hg of pressure at the ankle). Color duplex scanning was used to evaluate the possible presence of DVT; edema/swelling were evaluated with a composite score including the presence of edema (with an edema tester), variations in ankle circumference and leg volumetry, subjective swelling, and discomfort (scale ranging from 0 to 10). Results: Of the 103 included subjects in the stockings group and 108 in the control group (total 211), 195 subjects completed the study. Dropouts (16) were due to low compliance or traveling and connection problems. Age, sex distribution, and risk factors distributions were comparable in the 2 groups. Stockings Group: Of 97 subjects none had DVT or superficial thromboses. Control Group: Of 98 subjects none had thrombosis. The level of edema at inclusion was comparable in the 2 groups of subjects. After flights there was an average score of 6.4 (1.3) in the control group, while in the stockings group the score was on average 2.4 (SD 1), 2.6 times lower than in the control group (p < 0.05). In the control group 83% of the subjects had an evident increase in ankle circumference and volume that was visible at inspection and associated with discomfort. The control of edema with stockings was clear, considering both parametric data (circumference and volume) and nonparametric (analogue scale lines) measurements. Part II. In this part of the study 200 subjects at low-medium risk for DVT were contacted; 35 subjects were excluded for several nonmedical, travel-related problems or inconvenient evaluation time; the remaining 165 were randomized into 2 groups to evaluate prevention in flights lasting between 11 and 12 hours. The control group had no prophylaxis; the treatment group used Traveno stockings. Of the 83 included subjects in the stockings group and 82 in the control group (total 165), 146 subjects completed the study. Dropouts were due to low compliance or connection problems. Age/sex distribution were comparable. Of 75 subjects completing the study in the stockings group and 71 in the control group, none had thrombosis. The average level of edema at inclusion was comparable in the 2 groups (1.1). After the flight there was a score of 8.9 (2) in controls; in the stockings group the score was 2.56 (1.3) (p < 0.05). The control of edema and swelling with stockings even after 11 hours of flight was clear, considering both parametric (circumference, volume) and nonparametric (analogue scale lines) measurements. The tolerability of the stockings was very good and there were no complaints or side effects. In conclusion Sigvaris Traveno stockings are very effective in controlling edema in long-haul flights.     

Venous thromboembolism from air travel: the LONFLIT study.

The LONFLIT study was planned to evaluate the incidence of deep venous thrombosis (DVT) occurring as a consequence of long flights. In the Lonflit study 355 subjects at low-risk for DVT and 389 at high-risk were studied. Low-risk subjects had no cardiovascular disease and used no drugs. All flights were in economy class. The average flight duration was 12.4 hours (range, 10-15 hr). The mean age of the studied subjects was 46 years (range 20-80 yr, SD 11; 56% males). DVT diagnosis was made by ultrasound scans after the flights (within 24 hours). In low-risk subjects no events were recorded while in high-risk subjects 11 had DVT (2.8%) with 13 thromboses in 11 subjects and 6 superficial thromboses (total of 19 thrombotic events in 389 patients [4.9%]). In the Lonflit2 study the authors studied 833 subjects (randomized into 422 control subjects and 411 using below-knee stockings). Mean age was 44.8 years (range, 20-80 yr, SD 12; 57% males). The average flight duration was 12.4 hours. Scans were made before and after the flights. In the control group there were 4.5% of subjects with DVT while only 0.24% of subjects had DVT in the stockings group. The difference was significant. The incidence of DVT observed when subjects were wearing stockings was 18.75 times lower than in controls. Long-haul flights are associated to DVT in some 4-5% of high-risk subjects. Below-knee stockings are beneficial in reducing the incidence of DVT.     

Prevention of venous thrombosis in long-haul flights with Flite Tabs: the LONFLIT-FLITE randomized, controlled trial

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 treatments; 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 thrombotic 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.     

Prevention of venous thrombosis and thrombophlebitis in long-haul flights with pycnogenol.

The aim of this study was to evaluate the occurrence of deep venous thrombosis (DVT) and superficial vein thrombosis (SVT) and its prophylaxis with an oral anti-edema and antithrombotic agent (Pycnogenol, Horphag, Research Management SA, Geneva, Switzerland) in long-haul flights, in subjects at moderate to high-risk of DVT and SVT. The study pre-included 244 pre-selected subjects; 211 were included (33 were excluded for several reasons due to logistic problems) and 198 completed the study; 13 subjects were lost for follow-up at the end of the flight, all for non-medical problems (i.e., for difficult connections). All subjects were scanned within 90 minutes before the flight and within 2 hours after disembarking. Subjects were supplemented with 100 mg Pycnogenol per capsule. Treatment subjects received two capsules between 2 and 3 hours before flights with 250 mL of water; two capsules were taken 6 hours later with 250 mL of water and one capsule the next day. The control group received comparable placebo at the same intervals. The flight duration was on average 8 hours and 15 minutes (SD 55 min) (range, 7.45-12.33). In the control group there were five thrombotic events (one DVT and four superficial thromboses) while only nonthrombotic, localized phlebitis was observed in the Pycnogenol group (5.15% vs. no events; p<0.025). The ITT (intention to treat) analysis detects 13 failures in the control group (eight lost to follow up + five thrombotic events) of 105 subjects (12.4%) vs. five failures (4.7%; all lost, no thrombotic events) in the treatment group (p<0.025). No unwanted effects were observed. In conclusion, this study indicates that Pycnogenol treatment was effective in decreasing the number of thrombotic events (DVT and SVT) in moderate-to-high risk subjects, during long-haul flights.     

Venous thrombosis from air travel: the LONFLIT3 study--prevention with aspirin vs low-molecular-weight heparin (LMWH) in high-risk subjects: a randomized trial

The LONFLIT1 and 2 studies established that in high-risk subjects after long (>10 hours) flights, the incidence of deep venous thrombosis (DVT) may be between 4% and 6%, The LONFLIT3 study aimed to evaluate methods of prevention in high-risk subjects. Of 467 subjects contacted for the study, 300 were included. These 300 subjects at high risk for DVT were randomized, after informed consent, into three groups: 1) a control group that had no prophylaxis; 2) an aspirin treatment group, in which patients were treated with 400 mg (tablets of oral, soluble aspirin; one dose daily for 3 days, starting 12 hours before the beginning of the flight); and 3) a low-molecular-weight heparin (LMWH) group, in which one dose of enoxaparine was injected between 2 and 4 hours before the flight. The dose was weight-adjusted (1,000 IU [equivalent to 0.1 mL per 10 kg of body weight). Subjects with potential problems due to prophylaxis with aspirin or LMWH or at risk of drug interactions were excluded. Of the 100 included subjects in each group, a total of 249 subjects completed the study (dropouts due to low compliance or traveling/connections problems were 17%). Age and sex distribution were comparable in the three groups as well as risk distributions. Mean age was 47 (range, 28-75; SD, 11; 65% males). Of the 82 subjects in the control group, there were 4.82% of subjects with DVT with two superficial thromboses. In total 4.8% of limbs suffered a thrombotic event. Of 84 subjects in the aspirin treatment group, there were 3.6% of patients with DVT and three superficial thrombosis. In total 3.6% of limbs had a thrombotic event. In the LMWH group (82 subjects), there were no cases of DVT. One superficial thrombosis was documented. In total only 0.6% of limbs had a thrombotic event (p<0.002 in comparison with the other two groups). DVT was asymptomatic in 60% of subjects; 85% of DVTs were observed in passengers in non-aisle seats. Mild gastrointestinal symptoms were reported in 13% of patients taking aspirin. One dose of LMWH is an important option to consider in high-risk subjects during long-haul flights.     

Knee-length graduated compression stockings for thromboprophylaxis in air travellers: A meta-analysis

OBJECTIVE:

To systematically review the randomized controlled trials that have evaluated the efficacy of knee-length (KL) compression stockings for thromboprophylaxis in air travellers.

METHOD:

After an electronic database search, the randomized controlled trials that studied passengers on long-haul flights were selected and analyzed to generate summative data.

RESULTS:

Nine trials studying participants using KL stockings were analyzed. Forty-six of 1261 participants randomly assigned to the control group developed deep vein thrombosis (DVT), compared with two of 1237 participants (0.16%) in the KL stockings group. The weighted risk difference was −0.034, which indicated that the absolute difference was 3.4% in the incidence of DVT, in favour of KL stockings. The number needed to treat with KL stockings to avoid one case of DVT was 29.4. However, there was significant heterogeneity among trials. The RR for DVT was 0.08 in high-risk participants and 0.14 in low- to medium-risk participants.

CONCLUSION:

KL stockings are effective for thromboprophylaxis in air travellers at low, medium and high risk of DVT. The use of KL stockings should form an important part of air traveller education on lowering the burden of DVT. The results of the present meta-analysis can be used to advise travellers on their risk of DVT and preventive strategies.     

The LONFLIT4-Venoruton Study: a randomized trial--prophylaxis of flight-edema in venous patients

The aim of this independent study was to evaluate the protective effects, on the development of flight edema, of Venoruton. The study included patients with venous disease traveling in economy in long-haul flights (9 hours). Edema is a relevant aspect of long-haul flights affecting both patients with venous disease and normal subjects. Microcirculatory variations during flights cause a microangiopathy and biochemical and coagulation alterations. This condition may be defined as flight microangiopathy. A group of 203 subjects with chronic venous disease (uncomplicated varicose veins) at low-medium risk for DVT were contacted; 43 subjects were excluded for several nonmedical, travel-related problems or inconvenient evaluation time; the remaining 160 were randomized, after informed consent, into 2 groups to evaluate 2 prophylaxes in 7-8-hour, long-haul flights: The treatment group received Venoruton (hydroxyethyl rutosides) 1 g twice daily for 3 days (2 days before the flight and the day of the flight). The control group received comparable placebo. The edema score was based on the edema tester, ankle circumference, volume measurements, subjective swelling, and discomfort score. Items 1, 4, and 5 are based on an analogue scale line (1 to 10) directly defined by the subjects before and after the flights. Of the 160 included subjects 139 completed the study. Dropouts (21) were due to poor compliance, traveling, and/or connection problems (11 in the control group, 10 in the treatment group). Age and sex distribution were comparable in the 2 groups as were risk factors distributions. The level of edema at inclusion was comparable in the 2 groups of subjects. After the flight there was an average score of 7.2 (sd 2) in the control group, while in the Venoruton group the score was on average 3.2. (sd 1.1) (p < 0.05), 2.25 times lower than in the control group (p < 0.05). In the control group 89% of the subjects had an evident increase in ankle circumference and volume, which was clearly visible at inspection and associated with discomfort. In the Venoruton group edema was clearly present in 12% of subjects (associated with discomfort between 5 and 7 on the analogue scale line) and it was mild-moderate, not associated with symptoms (pain, discomfort between 2 and 4 on the analogue scale line). Therefore, the control of flight edema with Venoruton was clear both considering parametric data (circumference and volume) and nonparametric (analogue scale lines) measurements. The combined evaluation of the edema score is significantly favorable for patients treated with Venoruton. No deep vein thrombosis or superficial vein thrombosis was observed in this study.     

Air travel and the risk of thromboembolism

Almost two billion people use commercial aircraft annually. Long-haul flights are taken by over 300 million people. A serious complication of long-distance travel (or prolonged time of flight) is thromboembolism. The real incidence of the problem is difficult to evaluate since there is no consensus about the diagnostic tests or limitation of time after landing connected to the VTE complication. A direct relation between VTE incidence and long-distance flights has been documented. The risk for DVT is 3–12% in a long-haul flight. The pathophysiologic changes that increase VTE risk at flight are stasis (sitting in crowded condition), hypoxia in the airplane cabin, and dehydration. Individual risk factors for air travel-related VTE include age over 40 years, gender (female), women who use oral contraceptives, varicose veins in lower limbs, obesity and genetic thrombophilia. Prevention measures include environmental protection such as keeping the pressure inside the airplane cabinet in hypobaric condition, avoiding dehydration and prolonged sitting. For individuals at increased risk, venous blood stasis can be reduced by wearing elastic stockings and prophylactic use of low-molecular-weight heparin.     

Incidence of selected antiphospholipid antibodies in a group of patients with systemic lupus erythematosus

Antiphospholipid antibodies (APLA) present very heterogeneous groups of antibodies which can significantly and in various ways influence processes on different levels of coagulation cascade. Their presence can be accompanied with repetitive venous and arterial thromboses, recurrent loses of foetus, and thrombocytopenia. Incidence of these thrombotic disorders was monitored in a group of 46 patients with systemic lupus erythematodes (SLE). Positive lupus anticoagulant (LA), antiphospholipid antibodies complex, and thrombocyte counts were assessed. Thrombotic disorders were assessed in a retrospective analysis. In the LA+ group 62% of patients had history of venous thromboses, 31% had history of arterial thromboses, and 18% had history of spontaneous abortions. In a group without positive LA 18% of venous thromboses (p = 0.0006) and 6% of arterial thromboses (p = 0.03) were indicated. In the assessment of spontaneous abortions no statistically significant difference was found. An average value of thrombocytes in LA+ group was 152 +/- 66 x 10(5)/l, in LA- group 223 +/- 86 x 10(5)/l, which is statistically significant difference (p < 0.05). In the assessment of thrombotic disorders in a group with combination LA+ and APA+ statistical significance was indicated only in venous thromboses (p = 0.004). We can state from the results that in thrombotic disorders which can be seen in the framework of systemic tissue disorders positive LA and APA and a range of other factors such as activity of a basic disease, associated diseases, and treatment which can aggravate thrombotic disorders of individual patients can participate.     

Venous thrombosis after long-haul flights

BACKGROUND: The risk for venous thromboembolism after long-haul flights represents a controversial issue. The aim of our study was to assess the incidence of venous thrombosis associated with long-haul flights in a prospective, controlled cohort study. METHODS: We included 964 passengers returning from long-haul flights (flight duration, > or =8 hours) and 1213 nontraveling control subjects. We excluded participants who were being treated with anticoagulant drugs or who used compression stockings. Main outcome measures were the incidence of ultrasonographically diagnosed thrombosis in the calf muscle and deep veins, symptomatic pulmonary embolism, and death. RESULTS: We diagnosed venous thrombotic events in 27 passengers (2.8%) and 12 controls (1.0%) (risk ratio [RR], 2.83; 95% confidence interval [CI], 1.46-5.49). Of these, 20 passengers (2.1%) and 10 controls (0.8%) presented with isolated calf muscle venous thrombosis (RR, 2.52; 95% CI, 1.20-5.26), whereas 7 passengers (0.7%) and 2 controls (0.2%) presented with deep venous thrombosis (RR, 4.40; 95% CI, 1.04-18.62). Symptomatic pulmonary embolism was diagnosed in 1 passenger with deep venous thrombosis (P =.44). All of these individuals had normal findings at baseline ultrasonography. Passengers with isolated calf muscle venous thrombosis or deep venous thrombosis had at least 1 risk factor for venous thrombosis (>45 years of age or elevated body mass index in 21 of 27 passengers). The follow-up after 4 weeks revealed no further venous thromboembolic event. CONCLUSIONS: Long-haul flights of 8 hours and longer double the risk for isolated calf muscle venous thrombosis. This translates into an increased risk for deep venous thrombosis as well. In our study, flight-associated thrombosis occurred exclusively in passengers with well-established risk factors for venous thrombosis.     

Prevention of deep vein thrombosis in potential neurosurgical patients. A randomized trial comparing graduated compression stockings alone or graduated compression stockings plus intermittent pneumatic compression with control

In a randomized trial of neurosurgical patients, groups wearing graduated compression stockings alone (group 1) or graduated compression stockings plus intermittent pneumatic compression (IPC) (group 2) were compared with an untreated control group in the prevention of deep vein thrombosis (DVT). In both active treatment groups, the graduated compression stockings were continued for 14 days or until hospital discharge, if earlier. In group 2, IPC was continued for seven days. All patients underwent DVT surveillance with iodine 125-labeled fibrinogen leg scanning and impedance plethysmography. Venography was carried out if either test became abnormal. Deep vein thrombosis occurred in seven (8.8%) of 80 patients in group 1, in seven (9.0%) of 78 patients in group 2, and in 16 (19.8%) of 81 patients in the control group. The observed differences among these rates are statistically significant. The results of this study indicate that graduated compression stockings alone or in combination with IPC are effective methods of preventing DVT in neurosurgical patients.     

Multilayer compression bandaging in the acute phase of deep-vein thrombosis has no effect on the development of the post-thrombotic syndrome

Objective The purpose of this randomized study was to evaluate the influence of immediate multilayer compression bandages before application of elastic stockings in the acute phase of deep-vein thrombosis (DVT) on development of the post-thrombotic syndrome (PTS). Methods Sixty-nine patients with acute symptomatic DVT were randomized to immediate bandaging (n = 34) or no bandaging (n = 35). After reduction of edema sized-to-fit elastic stockings were applied in all patients after 7–14 days. Follow-up visits and non-invasive examinations were planned after 7, 30 and 90 days and 1 year. Venous outflow resistance (VOR) was measured by strain gauge plethysmography. Thrombosis score (TS) and reflux were measured by duplex scanning. After one year patients were evaluated for clinical PTS using both the clinical scale of the CEAP classification and the Villalta score. Results Improvement of clinical symptoms and decrease of leg circumference was better on day 7 in the bandaging group, but after 1 and 3 months clinical symptoms had improved equally in both groups. In 7 patients in the no-bandaging group a bandage was applied after all because of persistent edema after 10 days. There were no differences in VOR, TS and reflux. Using the CEAP classification the incidence of PTS was 39% in patients with bandages and 42% in patients without bandages (RR 0.91, 95% CI 0.50–1.66). Using the Villalta score the incidence of PTS was resp. 29 and 33% (RR 0.87, 95% CI 0.41–1.8). There was no difference in severity of PTS. Conclusion Immediate multilayer compression bandaging in the acute phase of DVT is effective in reducing edema and complaints in the first week, but has no effect on thrombus regression, valve incompetence and the development of clinical PTS after 1 year.     

Post‐thrombotic syndrome: prevalence,prognostication and need for progress

Despite considerable progress in the diagnosis and treatment of deep‐vein thrombosis (DVT) of the lower extremities, one of every 2–3 patients will develop within 2 years post‐thrombotic sequelae, which are severe in approximately 10% of cases and produce considerable socio‐economic consequences. Among factors potentially related to the development of the post‐thrombotic syndrome (PTS) are older age, obesity, a history of previous ipsilateral DVT, iliac‐femoral location of the current thrombosis, failure to promptly recover from the acute symptoms and insufficient quality of oral anticoagulant therapy. Based on recent findings, the lack of vein recanalization within the first 6 months after DVT appears to be an important predictor of PTS, while the role of venous reflux is controversial. According to the results of recent clinical studies, the prompt administration of adequate compression elastic stockings in patients with symptomatic DVT has the potential to halve the frequency of PTS, and when carefully supervised and instructed to wear proper elastic stockings, more than 50% of patients have the potential to either remain stable or improve during long‐term follow‐up. Nevertheless, due to limitations in current therapies, the management of PTS is demanding and often frustrating. Further research is required to optimize the prevention and management of this common and burdensome complication of DVT.     

Prevention of edema and flight microangiopathy with Venoruton (HR), (0-[beta-hydroxyethyl]-rutosides) in patients with varicose veins

The aim of this open study was the evaluation of the effects of HR (Venoruton) at a dose of 1 g/day on the prevention and control of flight microangiopathy and edema in subjects with varicose veins and moderate chronic venous insufficiency flying for more than 11 hours. Patients with varicose veins, edema, but without initial skin alterations or complications, were included. Measurements of skin laser Doppler (LDF) resting flux (RF) venoarteriolar response (VAR), ankle swelling (RAS), and edema were made within 12 hours before and within 3 hours after the flights. The resulting edema after the flights was evaluated with a composite edema score (analogue scale line). A group of 20 subjects was treated with HR (1 g/day, starting 2 days before the flight and 1 g for every 12 hours on day of travel). Another group of 18 subjects formed the control group. The length of the flights was between 11 and 13 hours; all seats were in coach class. Fifty patients were enrolled and 38 patients were evaluable at the end of the trial. The 2 groups (treatment and control) were comparable for age and sex distribution. The decrease in RF was significant in both groups with a higher flux at the end of the flight in the HR group (p < 0.05). The venoarteriolar response was decreased at the end of the flights; the decrease was lower in the HR group (p < 0.05). The increase in RAS and the edema score were significantly lower in the HR group. In conclusion HR is useful for reducing the level of microangiopathy and the increased capillary filtration and in controlling edema in patients with venous disease in long flights. The higher level of flux and VAR and the reduction in edema indicate a positive effect of HR on the microcirculation. This study confirms that HR prophylaxis is effective to control flight microangiopathy associated with edema.     

Prevention of edema in long flights with Pycnogenol.

The aim of this study was to evaluate the prevention of edema during long-haul flights with an oral, anti-edema and antithrombotic agent (Pycnogenol, Horphag, Research Management SA, Geneva, Switzerland) in asymptomatic subjects. The assessment of edema was performed by evaluating an analogue scale, the rate of ankle swelling by strain-gauge derived rate of ankle swelling (RAS), and by assessing the ankle circumference variation. The study included 211 subjects; 169 completed the study (88 in the control group and 81 in the Pycnogenol group). There were no important differences between the two groups (comparable for age, gender, weight, body mass index, and pattern distribution). The edema score, the RAS, and the circumference at inclusion were also comparable. After the flight in those treated with Pycnogenol, the edema score was increased only by 17.9% (vs. an increase of 58.3% in the control group) (p<0.05). The RAS, evaluated in 22 subjects in the Pycnogenol group (age 44.5; SD 8) and in 23 in the control group (age 45; SD 9) was increased on average by 91% in the control group and 36% in the Pycnogenol group (p<0.05). The variation on circumference at the ankle was 6% in the Pycnogenol group (11% in the control group; p<0.05). These results indicate a positive effect of Pycnogenol on edema during long flights when considering subjective and objective data. No unwanted effects were observed.     

Effects of factor V gene G1691A, methylenetetrahydrofolate reductase gene C677T, and prothombin gene G20210A mutations on deep venous thrombogenesis in Behçet's disease

OBJECTIVE: Beh?et's disease (BD) is a multisystemic disease of unknown etiology, characterized by aphthous ulcerations and uveitis, that is common in the Turkish population. Venous involvement is observed in 25% of the cases. While superficial thrombophlebitis is the most common finding, deep venous thrombosis (DVT) follows it. Hyperactivity in the coagulation pathway, hypoactive anticoagulation mechanisms, or faulty fibrinolysis generate a tendency for thrombogenesis. Mutations of the genes involved in these pathways may cause predisposition to thrombosis. METHODS: Possible roles of methylenetetrahydrofolate reductase (MTHFR) gene C677T, factor V (FV) gene G1691A (Leiden), and prothrombin gene G20210A polymorphisms in venous thrombogenesis were evaluated in patients with BD; 100 healthy people, 30 BD patients without DVT, 30 BD patients with DVT, and 30 patients with idiopathic DVT were studied with the restriction fragment length polymorphism method for these 3 polymorphisms. The frequencies of these mutations for each group, separately and in combinations, are described. RESULTS: Among the 3 mutations, FV Leiden mutation was found to be a risk factor for DVT. An association between FV Leiden mutation and BD was likely, but FV Leiden mutation did not increase the risk for deep venous thrombogenesis in BD patients. MTHFR gene C677T mutation does not increase risk of DVT in BD either alone or combined with FV Leiden mutation. CONCLUSION: Although a thrombotic tendency is one of the major characteristics of BD, we found no association between these 3 thrombogenetic mutations and BD patients with thromboses.     

Sex and age as prognostic factors in essential thrombocythemia.

BACKGROUND. The major causes of morbidity and mortality in essential thrombocythemia (ET) are bleeding and thrombotic accidents, but a prognostic pattern for these complications has not yet been discovered. MATERIALS AND METHODS. In this study we report data from a large cohort of patients with thrombocytosis, distinguished for sex and age, in order to define their thrombotic risk. The prevalence of vascular complications recognized in 86 patients with essential thrombocythemia was studied. In addition, 91 patients with polycythemia vera (PV), 20 with myelofibrosis (MF) and 63 with secondary thrombocytosis (ST) were evaluated. RESULTS. 6.3% of ET subjects younger than 40 (4.6% of males and 7.0% of females), 11.8% of patients between 40 and 65 years old (14.9% of males and 9% of females), and 16.8% of subjects over 65 (14.6% of males and 17.8% of females) showed thrombotic accidents. In the PV and MF groups thromboses occurred more frequently than in the ET groups for all ages and for both sexes. On the contrary, ST subjects showed fewer thromboses than ET patients, but their incidence rose with patient age; moreover the prevalence of males in this group was limited. In ET patients, particularly in females, the incidence of thrombosis was low under 40 years of age, but rapidly increased later. CONCLUSIONS. ET females over 40 must be followed with particular attention in order to prevent thrombotic complications.     

Prevention and treatment of postphlebitic syndrome: results of a 3-part study

BACKGROUND: The true incidence of postphlebitic syndrome (PPS) following proximal deep venous thrombosis (DVT) and the efficacy of graduated compression stockings in preventing and treating PPS are unknown. METHODS: A 3-part study of 202 patients evaluated 1 year after proximal DVT: 2 randomized placebo-controlled trials of stockings and 1 prospective cohort of untreated patients. Patients were evaluated for PPS, using a standardized questionnaire, and for venous valvular incompetence, using photoplethysmography and venous Doppler. They were enrolled in study 1 or study 2 if they did not have symptomatic PPS and did not have or had venous valvular incompetence, respectively, and into study 3 if they had symptomatic PPS. Study 1 patients were left untreated and followed up for development of PPS every 6 months for a mean of 55 months. Study 2 patients were randomized to a below-knee stocking (20-30 mm Hg) or a matched placebo stocking, and followed up for development of PPS every 6 months for a mean of 57 months. Study 3 patients were randomized to an active stocking (30-40 mm Hg) or a matched placebo stocking and followed up every 3 months for treatment failure, defined a priori. RESULTS: In study 1, 6 (5.0%) of 120 patients were categorized as treatment failures, a rate similar to placebo-treated study 2 patients (P =.10). In study 2, 0 (0%) of 24 active and 1 (4.3%) of 23 placebo-treated patients were categorized as treatment failures (P =.49). In study 3, 11 (61.1%) of 18 active and 10 (58.8%) of 17 placebo-treated patients were categorized as treatment failures (P>.99). CONCLUSIONS: Most patients do not have PPS 1 year after proximal DVT, and do not require stockings. We failed to show a benefit of stockings in patients with PPS, but the small numbers preclude definitive conclusions.