Flying while pregnant: what is the thrombosis risk?

Abstract

Physicians are encouraged to risk stratify pregnant and post-partum travelers into low, intermediate and high risk for venous thromboembolism. In the average healthy pregnant or postpartum woman, the risk of travel-associated venous thromboembolism appears low (< 1%), warranting only routine, common sense preventive measures. However, higher risk women may warrant thromboprophylaxis.

Highlight

Physicians are encouraged to risk stratify pregnant and post-partum travellers into low, intermediate and high risk for venous thromboembolism. In the average healthy pregnant or post-partum woman, the risk of travel-associated venous thromboembolism appears low (<1%), warranting only routine, common sense preventive measures. However, higher risk women may warrant thromboprophylaxis.

Editorial

Air travel is a common means of transportation, and pregnant women frequently travel by plane. Due to physiological changes that take place during normal pregnancy, the risk of venous thromboembolism (VTE) (which includes deep vein thrombosis (DVT) and pulmonary embolism) is increased both during the antepartum and post-partum periods, compared with not being pregnant. Taking a long-haul flight also increases the risk of VTE, compared with not flying. Theoretically, the combination of pregnancy and air travel may further increase the risk of VTE; however, there are limited data on the absolute risk of VTE in the pregnant traveller, if the risk is additive or multiplicative, whether it is appropriate to institute prophylactic measures to reduce this risk. In this issue, Karsanji et al. provide a comprehensive, case-based review of the published literature and guidelines on this topic.¹ Based on the level of risk, they recommend measures to prevent air travel-associated VTE in pregnant and post-partum women, which are accompanied by appropriate caveats in view of the lack of supporting data in this population.

What data are available? In terms of risk of VTE with travel, a meta-analysis of 14 studies representing 4055 cases of VTE revealed that air travel was associated with a 3-fold risk of VTE (RR 2.8; CI 2.2–3.7), and this risk showed a dose-response relationship with a 26% higher risk for every 2 hours of air travel.² The absolute risk of developing a symptomatic episode of DVT during the 8 weeks after long-haul flight (defined as a flight of at least 4 hours) was 1 in 4656.³ Airline passengers sit for prolonged hours, which can lead to venous stasis and minor vessel injury, and while controversial, the hypobaric airplane environment may induce a state of hypercoagulability.

In terms of risk of VTE with pregnancy, during the combined pregnancy and post-partum period, the risk is 1.2 per 1000 deliveries (95% CI, 0.6–1.8 per 1000), with an estimated risk of 0.6/1000 in the antepartum and 0.6/1000 in the post-partum period.⁴ The MEGA study reported a 5-fold (OR 4.6 95% CI 2.7–7.8) increased risk of VTE during pregnancy, with a particularly high risk during the first 6 weeks post-partum (OR 84; 95% CI 31.7–222.6).⁵ Pregnancy increases the risk of VTE through all three elements of Virchow’s triad. Hormone-induced venodilatation and compression of the inferior vena cava and iliac veins by the gravid uterus lead to stasis of venous blood in the lower extremities. Pregnancy-induced alterations in pro- and anti-coagulant factors lead to a hypercoagulable and hypofibrinolytic state, respectively. Lastly, delivery leads to endothelial injury, which can promote thrombus formation post-partum.

Karsanji et al. in their review article provide an indirect estimate of the absolute risk of VTE in the pregnant traveller by multiplying the current known risk of VTE in pregnancy or post-partum (0.6/1000)⁴ by the relative risk of VTE in long-haul travellers (2.8), which equals a calculated VTE risk of 1.7 per 1000 pregnant or post-partum travellers. However, as they explain, this calculation assumes that the risk of the flight lasts for the entire duration of the pregnancy, which is not the case. As the risk of VTE extends to 8 weeks after travel, and assuming that pregnant women do not travel past 36 weeks of gestation, the risk of venous thrombosis in most pregnant travellers after one flight can be calculated by multiplying 1.7 per 1000 by 8/36, which yields a lower risk of ~0.4 per 1000 (0.04%) pregnant or post-partum travellers.

However, in pregnant travellers with additional VTE risk factors, such as inherited thrombophilia, obesity or recent surgery, the risk of VTE is likely higher. Performing similar calculations, Karsanji et al. extrapolated the estimated VTE risk during pregnancy after a single flight for various thrombophilias. Women with rare, severe forms of thrombophilia such as homozygous Factor V Leiden, homozygous prothrombin gene mutation and severe antithrombin deficiency should already be on VTE prophylaxis throughout pregnancy as per current guidelines, regardless of whether they travel. For the common thrombophilias (e.g. heterozygous Factor V Leiden or prothrombin gene mutations), the risk of travel-associated VTE is still low, estimated at < 1%, which is suggested by the authors as the risk threshold point below which thromboprophylaxis may not be required. However, in post-partum woman with certain thrombophilias, the additional risk of travel based on calculated estimates can raise the VTE risk to > 1%, especially if there is a family history of VTE, such that pharmacologic prophylaxis to cover the period of travel may be indicated.

A unique aspect of Karsanji et al.’s review is their calculation of the risk of travel-associated VTE in pregnant women at different levels of VTE risk, e.g. women with and without thrombophilia, and in the antepartum and post-partum period. These calculations are made based on a multiplicative effect, which they acknowledge is an assumption.

For VTE risk in pregnant travellers without known thrombophilia (the majority of pregnant travellers), the calculation method noted above yields the risk estimates of low magnitude, < 1%, and if the relative risks of VTE in pregnancy and air travel are added rather than multiplied, the risk estimate is even lower, at 0.3 per 1000 pregnant travellers. These extrapolated indirect measures signal a low risk of VTE after a single episode of air travel in the average pregnant woman without additional risk factors.

The important take-home message is that it is prudent for physicians to risk stratify pregnant travellers into low, intermediate and high risk. In low-risk women (defined by Karsanji et al. as a risk of < 1%), prevention can be limited to common sense measures such as frequent ambulation, calf muscle exercises, avoiding restrictive clothing and minimizing baggage in the space under the seat so the legs are free to stretch. High-risk pregnant women with a prior history of unprovoked VTE (i.e. no apparent reversible risk factors), oestrogen-related (pregnancy, oral contraceptives) VTE or potent thrombophilia should already be on low molecular weight heparin (LMWH) for VTE prophylaxis in the antepartum period, and if not, may warrant LMWH prophylaxis prior to flying. In pregnant women with minor risk factors such as heterozygous factor V Leiden or prothrombin gene mutation, the risk of VTE with air travel is likely low (<1%). However, in the post-partum state, various thrombophilias can increase the VTE risk with travel to above 1%, such that thromboprophylaxis may be warranted. Finally, in other increased-risk women such as those with previous provoked VTE, recent surgery or trauma, limited mobility or obesity, the magnitude of additional risk brought on by the combination of pregnancy and air travel is currently not known. However, the combination of three or more risk factors likely warrants thromboprophylaxis during air travel. In terms of options for thromboprophylaxis, LMWH is the medication of choice for pregnant and post-partum breastfeeding women. Graduated compression stockings are also reasonable for VTE prevention during travel, although this is based only on limited quality evidence.

Finally, in addition to assessing thrombotic risk, it is our responsibility as health care providers to educate pregnant travellers on symptoms and signs of DVT and PE. Dyspnea and lower extremity edema frequently occur during normal pregnancy, and pregnant women should be made aware of when it may be time to seek urgent care.