A. J. M. Schreijer

Activation of coagulation system during air travel: a crossover study

BACKGROUND There is an increased risk of venous thrombosis after air travel, but the underlying mechanism is unclear. Our aim was to ascertain whether flying leads to a hypercoagulable state. METHODS We did a crossover study in 71 healthy volunteers (15 men, 56 women), in whom we measured markers of activation of coagulation and fibrinolysis before, during, and after an 8-h flight. The same individuals participated in two control exposure situations (8-h movie marathon and daily life) to separate the effect of air travel on the coagulation system from those of immobilisation and circadian rhythm. To study the effect of risk factors for thrombosis, we included participants with the factor V Leiden mutation (n=11), those who took oral contraceptives (n=15), or both (n=15), as well as 30 individuals with no specific risk factors. FINDINGS After the flight, median concentrations of thrombin-antithrombin (TAT) complex increased by 30.1% (95% CI 11.2-63.2), but decreased by 2.1% (-11.2 to 14) after the cinema and by 7.9% (-16.2 to -1.2) after the daily life situation. We recorded a high response in TAT levels in 17% (11 of 66) of individuals after air travel (3% [2 of 68] for movie marathon; 1% [1 of 70] in daily life). These findings were most evident in the group with the factor V Leiden mutation who used oral contraceptives. We noted a high response in all variables (prothrombin fragment 1 and 2, TAT, and D-dimer) in four of 63 (6.3%) volunteers after the flight, but in no-one after either of the control situations. INTERPRETATION Activation of coagulation occurs in some individuals after an 8-h flight, indicating an additional mechanism to immobilisation underlying air travel related thrombosis.

Travel and venous thrombosis : a systematic review

Abstract.  Kuipers S, Schreijer AJM, Cannegieter SC, Büller HR, Rosendaal FR, Middeldorp S (Leiden University Medical Center, Leiden; and Academic Medical Center, Amsterdam; and Leiden University Medical Center, Leiden, the Netherlands). Travel and venous thrombosis: a systematic review (Review). J Intern Med 2007; 262: 615–634.

The effect of flight-related behaviour on the risk of venous thrombosis after air travel

In a case–control study including 11 033 participants (The Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis study) on risk factors of venous thrombosis, we studied the effect of flight‐related behaviour on the risk of venous thrombosis after air travel. Patients and control subjects received a questionnaire on risk factors for venous thrombosis, including recent travel history and details of their last flight. From this population, 80 patients and 108 control subjects were selected who had recently (<8 weeks) travelled for more than 4 h by aeroplane. Window seating compared to aisle seating increased the risk twofold [odds ratio (OR) 2·2; 95% confidence interval (CI): 1·1–4·4], particularly in those who were obese (OR 6·1; 95% CI: 0·5–76·2). Anxiety (OR 2·5; 95% CI: 0·9–7·0) and sleeping (OR 1·5; 95% CI: 0·7–3·1) may increase the risk slightly. The risk was not affected by alcohol consumption (OR 1·1; 95% CI: 0·5–2·4). Flying business class may lower the risk (OR 0·7; 95% CI: 0·2–1·8). We did not find a protective effect for several measures currently part of standard advice from airlines and clinicians, i.e. drinking non‐alcoholic beverages, exercising or wearing stockings. The effect of behavioural factors during flying on the risk of venous thrombosis after air travel is limited. Current advice on prevention of travel‐related thrombosis may have to be reconsidered.

Explanations for coagulation activation after air travel

Summary.  Background: It is unknown whether venous thrombosis after long haul air travel is exclusively attributable to immobilization. Objectives: We determined whether the following mechanisms were involved: hypoxia, stress, inflammation or viral infection. Patients/Methods: In a case crossover setting in 71 healthy volunteers who were exposed to an 8‐h flight, 8‐h movie marathon and 8 h of regular activities, we compared markers for several hypothetical pathways: plasminogen activator inhibitor‐1 (PAI‐1), stress, plasma factor (F)VIII coagulant activity (FVIIIc), soluble P‐selectine (sP‐selectine), interleukin‐8 (IL‐8) and neutrophil elastase. We reported earlier an activated clotting system, as evidenced by thrombin generation, in 17% of volunteers after the flight. Results: PAI‐1 increased by 4.2 ng mL−1 (CI95:−49.5 to 6.5) in volunteers with an activated clotting system whereas it decreased in those without (−20.0 ng mL−1, CI95:−33.2 to −14.0). FVIIIc levels rose more in individuals with clotting activation (18.0%, CI95:−1.0 to 33.0) than in those without (2.0%, CI95:−2.0 to 5.0). The increases in FVIIIc were not associated with stress, which appeared unrelated to clotting activation. sP‐selectin increased in those with clotting activation (3.5 μg L−1, CI95: −3.0 to 10.0), but decreased in those without (−0.5 μg L−1, CI95: −2.0 to 2.0). Changes in levels of neutrophil elastase or IL‐8 were not different between the subjects with and without clotting activation. Conclusions: Our results do not support the hypotheses that stress, infection or air pollution are involved in the development of a prothrombotic state in air travellers. After long haul air travel, this state is more pronounced in patients with risk factors and may be caused by hypoxia, triggering systemic inflammation and platelet activation, leading to coagulation induction and degranulation of platelets.

Fluid loss does not explain coagulation activation during air travel

The mechanism of air travel-related venous thrombosis is unclear. Although immobility plays a pivotal role, other factors such as fluid loss may contribute. We investigated whether fluid loss occurred more in individuals with coagulation activation after air travel than in subjects without. As a secondary aim, we investigated whether fluid loss per se occurred during air travel. In this crossover study, 71 healthy volunteers were exposed to eight hours of air travel, eight hours immobilization in a cinema, and a daily-life control situation. Markers of fluid loss (haematocrit, serum osmolality and albumin) and of coagulation activation were measured before and after each exposure. The study included 11 volunteers with and 55 volunteers without coagulation activation during the flight. The change in parameters of fluid loss was not different in volunteers with an activated clotting system from those without (difference between groups in haematocrit: -0.6%, 95% confidence interval [CI]: -1.9 to 0.6). On a group level, mean haematocrit values decreased during all three exposures. However, in some individuals it increased, which occurred in more participants during the flight (34%; 95% CI 22 to 46) than during the daily-life situation (19%; 95% CI 10 to 28). These findings do not support the hypothesis that fluid loss contributes to thrombus formation during air travel.

High hematocrit as a risk factor for venous thrombosis. Cause or innocent bystander

In the lay press it is frequently stated that long haul air travel causes venous thrombosis through dehydration in the airplane, leading to hyperviscosity of the blood, which in its turn favors thrombosis. The common advice that is given to prevent thrombosis after air travel is, therefore, ‘to

No effect of isolated long‐term supine immobilization or profound prolonged hypoxia on blood coagulation

Long‐distance air travel is associated with an increased risk of venous thrombosis. The most obvious factor that can explain air travel–related thrombosis is prolonged seated immobilization. In addition, hypobaric hypoxia has been shown to affect coagulation, and the lowered atmospheric pressures present in the cabin during the flight may therefore play an etiologic role. Because immobilization and hypoxic conditions are usually present simultaneously in airplanes or hypobaric chambers, their separate effects on the coagulation system or on thrombosis risk have not been studied extensively.

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

M. COPPENS ,* A . J . M . SCHRE I J ER ,* F . H . BERGER , S . C . CANNEGIETER , F . R . ROSENDAAL § and H . R . B Ü LLER* *Department of Vascular Medicine, Academic Medical Center, Amsterdam; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden; Department of Radiology, Academic Medical Center, Amsterdam; and §Department of Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, the Netherlands