Thromboembolism Not Linked to Cabin Pressure

The low-air-pressure, hypoxic environment experienced in air travel is not likely a cause of the increased risk for venous thromboembolism associated with long-distance flight, a team of British and Dutch researchers has reported.

The investigators, led by Dr. William D. Toff of the University of Leicester (England), performed a single-blind crossover study to compare the effects of a simulated long-haul flight—prolonged sitting in a hypobaric, hypoxic environment—with the effects of prolonged sitting in a normobaric, normoxic control environment.

Study participants in both groups showed significant changes in measures of several blood markers associated with thrombolysis, but these changes were not significantly different between the two exposure environments and were ascribed to circadian rhythm and the act of prolonged sitting, rather than to lowered atmospheric pressure (JAMA 2006;295:2251–61).

A total of 73 participants were screened for factor V Leiden and prothrombin G202190 mutations (the most common causes of thrombophilia) and stratified into three groups according to their risk of thromboembolism: a younger group (49 people; age 18–40 years; mean 23.5 years) not taking oral contraceptives, a smaller group of oral contraceptive users (12 people; age 18–40 years; mean 23.8 years), and an older group of men and women (12 people; age at least 50 years; mean age 57 years).

The researchers then randomly assigned all participants to one of two exposure groups, which differed only in the order of exposure. One group first sat for 8 hours in a bariatric chamber pressurized to create an environment of hypobaric hypoxia equal to roughly 8,000 feet (the lowest cabin pressure permitted by airline regulations) and 1 week later sat for another 8 hours in the chamber under normobaric normoxia; the second group underwent the same exposure but in the reverse order. Participants were allowed to stand up and move for 5 minutes each hour, could drink nonalcoholic beverages, and were given a light lunch and snacks.

The investigators recorded arterial oxygen saturation via pulse oximetry every hour and took blood samples before and after each 8-hour session to assess coagulation activation, fibrinolysis, platelet activation, and endothelial cell activation for each participant.

As expected, all three risk groups experienced lower arterial oxygen saturation during the low-pressure portion of the study. Notably, though, statistically significant changes were seen in markers of coagulation activation and fibrinolysis during not only the hypobaric exposure but also the normobaric (control) session—leading the investigators to conclude that such changes were associated with long-term sitting and natural circadian patterns, rather than air pressure. For example, the level of tissue plasminogen activator dropped a median of 1.23 ng/mL during normobaric normoxia and a median of 1.00 ng/mL during hypobaric hypoxia.

In addition, these changes were not significantly different between normal pressure and lower pressure for any of the three risk groups.

“In this large, controlled study with measurement of a wide range of markers … we found no procoagulant changes attributable to hypobaric hypoxia,” the investigators concluded. “Our findings do not support the hypothesis that hypobaric hypoxia of the degree that might be encountered during long-haul air travel is associated with prothrombotic alterations in the hemostatic system in healthy individuals at low risk of venous thromboembolism.”

The researchers did not comment on whether the changed blood marker levels, corresponding with increased risk for venous thromboembolism, are in themselves cause for concern. However, they called these changes “minor.”

“It is noteworthy that there was no significant change in endogenous thrombin potential, a global marker of coagulation activation,” they added. In some individuals, genetic risk factors might interact with hypoxia to increase the risk of thromboembolism, they conceded.

The study authors noted that reports of venous thromboembolism after long-haul air travel began more than 50 years ago.

In an accompanying editorial, Dr. Peter Bäärtsch of the University of Heidelberg (Germany) concurred with the study authors that mild hypoxia and prolonged sitting pose little risk to most people but added that “the small numbers of older participants and individuals taking contraceptives preclude drawing reliable conclusions about these groups” (JAMA 2006;295:2297–9).

The study was funded by the U.K. Department for Transport, the U.K. Department of Health, and the European Commission.

The low-air-pressure, hypoxic environment experienced in air travel is not likely a cause of the increased risk for venous thromboembolism associated with long-distance flight, a team of British and Dutch researchers has reported.

The investigators, led by Dr. William D. Toff of the University of Leicester (England), performed a single-blind crossover study to compare the effects of a simulated long-haul flight—prolonged sitting in a hypobaric, hypoxic environment—with the effects of prolonged sitting in a normobaric, normoxic control environment.

Study participants in both groups showed significant changes in measures of several blood markers associated with thrombolysis, but these changes were not significantly different between the two exposure environments and were ascribed to circadian rhythm and the act of prolonged sitting, rather than to lowered atmospheric pressure (JAMA 2006;295:2251–61).

A total of 73 participants were screened for factor V Leiden and prothrombin G202190 mutations (the most common causes of thrombophilia) and stratified into three groups according to their risk of thromboembolism: a younger group (49 people; age 18–40 years; mean 23.5 years) not taking oral contraceptives, a smaller group of oral contraceptive users (12 people; age 18–40 years; mean 23.8 years), and an older group of men and women (12 people; age at least 50 years; mean age 57 years).

The researchers then randomly assigned all participants to one of two exposure groups, which differed only in the order of exposure. One group first sat for 8 hours in a bariatric chamber pressurized to create an environment of hypobaric hypoxia equal to roughly 8,000 feet (the lowest cabin pressure permitted by airline regulations) and 1 week later sat for another 8 hours in the chamber under normobaric normoxia; the second group underwent the same exposure but in the reverse order. Participants were allowed to stand up and move for 5 minutes each hour, could drink nonalcoholic beverages, and were given a light lunch and snacks.

The investigators recorded arterial oxygen saturation via pulse oximetry every hour and took blood samples before and after each 8-hour session to assess coagulation activation, fibrinolysis, platelet activation, and endothelial cell activation for each participant.

As expected, all three risk groups experienced lower arterial oxygen saturation during the low-pressure portion of the study. Notably, though, statistically significant changes were seen in markers of coagulation activation and fibrinolysis during not only the hypobaric exposure but also the normobaric (control) session—leading the investigators to conclude that such changes were associated with long-term sitting and natural circadian patterns, rather than air pressure. For example, the level of tissue plasminogen activator dropped a median of 1.23 ng/mL during normobaric normoxia and a median of 1.00 ng/mL during hypobaric hypoxia.

In addition, these changes were not significantly different between normal pressure and lower pressure for any of the three risk groups.

“In this large, controlled study with measurement of a wide range of markers … we found no procoagulant changes attributable to hypobaric hypoxia,” the investigators concluded. “Our findings do not support the hypothesis that hypobaric hypoxia of the degree that might be encountered during long-haul air travel is associated with prothrombotic alterations in the hemostatic system in healthy individuals at low risk of venous thromboembolism.”

The researchers did not comment on whether the changed blood marker levels, corresponding with increased risk for venous thromboembolism, are in themselves cause for concern. However, they called these changes “minor.”

“It is noteworthy that there was no significant change in endogenous thrombin potential, a global marker of coagulation activation,” they added. In some individuals, genetic risk factors might interact with hypoxia to increase the risk of thromboembolism, they conceded.

The study authors noted that reports of venous thromboembolism after long-haul air travel began more than 50 years ago.

In an accompanying editorial, Dr. Peter Bäärtsch of the University of Heidelberg (Germany) concurred with the study authors that mild hypoxia and prolonged sitting pose little risk to most people but added that “the small numbers of older participants and individuals taking contraceptives preclude drawing reliable conclusions about these groups” (JAMA 2006;295:2297–9).

The study was funded by the U.K. Department for Transport, the U.K. Department of Health, and the European Commission.

The low-air-pressure, hypoxic environment experienced in air travel is not likely a cause of the increased risk for venous thromboembolism associated with long-distance flight, a team of British and Dutch researchers has reported.

The investigators, led by Dr. William D. Toff of the University of Leicester (England), performed a single-blind crossover study to compare the effects of a simulated long-haul flight—prolonged sitting in a hypobaric, hypoxic environment—with the effects of prolonged sitting in a normobaric, normoxic control environment.

Study participants in both groups showed significant changes in measures of several blood markers associated with thrombolysis, but these changes were not significantly different between the two exposure environments and were ascribed to circadian rhythm and the act of prolonged sitting, rather than to lowered atmospheric pressure (JAMA 2006;295:2251–61).

A total of 73 participants were screened for factor V Leiden and prothrombin G202190 mutations (the most common causes of thrombophilia) and stratified into three groups according to their risk of thromboembolism: a younger group (49 people; age 18–40 years; mean 23.5 years) not taking oral contraceptives, a smaller group of oral contraceptive users (12 people; age 18–40 years; mean 23.8 years), and an older group of men and women (12 people; age at least 50 years; mean age 57 years).

The researchers then randomly assigned all participants to one of two exposure groups, which differed only in the order of exposure. One group first sat for 8 hours in a bariatric chamber pressurized to create an environment of hypobaric hypoxia equal to roughly 8,000 feet (the lowest cabin pressure permitted by airline regulations) and 1 week later sat for another 8 hours in the chamber under normobaric normoxia; the second group underwent the same exposure but in the reverse order. Participants were allowed to stand up and move for 5 minutes each hour, could drink nonalcoholic beverages, and were given a light lunch and snacks.

The investigators recorded arterial oxygen saturation via pulse oximetry every hour and took blood samples before and after each 8-hour session to assess coagulation activation, fibrinolysis, platelet activation, and endothelial cell activation for each participant.

As expected, all three risk groups experienced lower arterial oxygen saturation during the low-pressure portion of the study. Notably, though, statistically significant changes were seen in markers of coagulation activation and fibrinolysis during not only the hypobaric exposure but also the normobaric (control) session—leading the investigators to conclude that such changes were associated with long-term sitting and natural circadian patterns, rather than air pressure. For example, the level of tissue plasminogen activator dropped a median of 1.23 ng/mL during normobaric normoxia and a median of 1.00 ng/mL during hypobaric hypoxia.

In addition, these changes were not significantly different between normal pressure and lower pressure for any of the three risk groups.

“In this large, controlled study with measurement of a wide range of markers … we found no procoagulant changes attributable to hypobaric hypoxia,” the investigators concluded. “Our findings do not support the hypothesis that hypobaric hypoxia of the degree that might be encountered during long-haul air travel is associated with prothrombotic alterations in the hemostatic system in healthy individuals at low risk of venous thromboembolism.”

The researchers did not comment on whether the changed blood marker levels, corresponding with increased risk for venous thromboembolism, are in themselves cause for concern. However, they called these changes “minor.”

“It is noteworthy that there was no significant change in endogenous thrombin potential, a global marker of coagulation activation,” they added. In some individuals, genetic risk factors might interact with hypoxia to increase the risk of thromboembolism, they conceded.

The study authors noted that reports of venous thromboembolism after long-haul air travel began more than 50 years ago.

In an accompanying editorial, Dr. Peter Bäärtsch of the University of Heidelberg (Germany) concurred with the study authors that mild hypoxia and prolonged sitting pose little risk to most people but added that “the small numbers of older participants and individuals taking contraceptives preclude drawing reliable conclusions about these groups” (JAMA 2006;295:2297–9).

The study was funded by the U.K. Department for Transport, the U.K. Department of Health, and the European Commission.