The WRIGHT (World Health Organisation Research Into Global Hazards of Travel) is a multi-centred multi-study project investigating the association between travel and venous thrombo-embolism (VTE), a term which covers deep vein thrombosis (DVT) and/or pulmonary embolism (PE).
The project was carried out according to the WRIGHT protocol, and overseen by the Scientific Executive Committee (SEC), consisting of Dr P J Kesteven (chairman), Dr W D Toff, Prof F Paccaud, Prof H R Büller, Prof M Greaves, Dr S Mendis and Prof F.R. Rosendaal.
The WRIGHT project was designed as a series of inter-related studies with the following aims:
- to determine if the risk of venous thrombosis is increased by air travel;
- to determine the magnitude of this risk;
- to determine the effect of other factors on the association;
- to clarify the causal mechanisms.
Furthermore, these studies were performed in several general settings which included clinical endpoints (i.e., symptomatic disease) and surrogate endpoints (i.e., markers of coagulation). The studies were organised into two groups:
1. Epidemiological studies MEGA study:
Data were collected from consecutive patients, aged less than 70 years, presenting to 6 anticoagulation clinics in the Netherlands with a first VTE. Partners served as matched controls. Information was collected by questionnaire on acquired risk factors, and genetic risk factors for VTE were determined on a blood sample. Cases of VTE were verified with hospital records and only objectively diagnosed cases were included in the analysis.
Professional Flyers Study: a retrospective cohort study amongst employees of international companies and organisations. Data concerning occurrence of VTE, risk factors for VTE and habits during air travel were linked to the organisation's travel databases. Exposure was defined as 4 weeks after a 4 hour flight.
Dutch Commercial Pilots Study: A questionnaire was sent to all members of the Dutch Airline Pilots Association who were younger than 55 years on 31 December 2002. Data concerning occurrence of VTE, risk factors for VTE and flight data were included.
2. Patho-physiological studies Chamber Studies:
Forty nine healthy subjects with no known risks of VTE, and a further 24 subjects with mild risk (12 using oral contraception and 12 aged >50 years) were seated in low atmospheric pressure and low oxygen level conditions for 8 hours, simulating flight in a commercial airliner. As a control, the subjects also sat in an identical situation in normal atmospheric pressure and oxygen level. These studies were performed in random order. A large number of haemostatic variables were assessed (involving markers of activation of coagulation, endothelium, platelets and fibrinolysis) before and after these exposures.
Volunteer Study: In a similar study, 71 healthy volunteers flew in a chartered commercial airliner for 8 hours, with the same haemostatic variables assessed before, during and after the flight. Risks factors for venous thrombosis were more abundant in this group: 26 asymptomatic carriers of the factor V Leiden mutation and 30 women using oral contraceptives (15 with, and 15 without the mutation). Two control situations were used - 8 hours watching movies and 8 hours of normal day-to-day activity
The combined results from this group of studies provide a consistent picture, in line with previous medical literature on travellers' thrombosis. However, these data strengthen this picture in as much as far greater numbers have been involved in these studies than ever collected in previous publications. Furthermore, they make a large contribution to fleshing out the specific individual risks of this complication.
As previously suspected, it is clear from the epidemiological studies that seated immobility is a risk factor for VTE. When considering the whole population, this risk appears to be small (approximately three-fold increase) and to be present whatever form of travel. These studies confirm that the longer the period of travel, the greater the risk. Multiple flights in a short period probably reflect the same phenomenon. The epidemiological studies also highlighted the fact that the relative risk of travellers' thrombosis increases sharply if other risks for VTE are present. These results are supported by the patho-physiological studies.
Taken overall, there were no changes in any coagulation parameters during an 8-hour flight or during a similar period of hypobaric hypoxia in a hypobaric chamber (compared to control situations). Careful analysis of the data from the Volunteer Study (which included subjects at increased risk for VTE) demonstrated a small population of 'hyper-responders'. This was not so obvious in the Chamber Studies (in which only subjects at low or modestly increased risk for VTE were included.
Air operators and Health and safety executives need to be aware of the following risk factors for VTE:
- seated immobility.
A small risk is present in all forms of travel and for all people. The risk is increased with longer periods of travel. Risk increases if other risks for VTE are present.
No results directly relevant to this theme. However, please note that some findings relevant to the project's key theme (Air) are generically applicable.
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No policy implications directly relevant to this theme. However, please note that some policy implications relevant to the project's key theme (Air) are generically applicable.