**4. Recommendations**

Nearly 50% of the passengers with DVT of one or more extremities may be asymptomatic. However, edema of the limb, pain, and signs as red and hot to touch skin are some of the symptoms. Unspecific symptoms of pulmonary embolism may be present, such as unexplained dyspnea, abnormal heart rhythm, chest pain, intolerance that may be aggravated by coughing or deep inhalation, coughing up blood, anxiety, dizziness, or a tendency to faint. Especially, people in high-risk groups should be informed about early recognition of these symptoms in order to seek for medical help. Preventive measures include sufficient hydration, avoidance of alcohol/excessive caffeine intake, and regular walking during the trip.

The risk of VTE is eightfold increased in patients with the factor V Leiden mutation that affects blood clotting. These passengers should be considered for heparin prophylaxis. According to the French Society of Cardiology, the probability

**157**

long-haul flights.

**4.2 Immobilization**

*Vein Thrombosis Risk in Women and Travel DOI: http://dx.doi.org/10.5772/intechopen.92229*

aisle seat, if you are predisposed to VTE.

estimated absolute risk of 1/109 flights [2, 23–25].

**4.1 Pregnancy and travel**

consideration:

of venous thrombosis during an airline flight is multiplied by 2.81 in a healthy person, regardless of flight time. The risk is then increased by 26% for every 2 h of flight. Before traveling it is prudent to take the following recommendations into

administration of low molecular weight heparin 2–6 h before traveling.

Wear comfortable clothing, leave space under the front seat to allow mobility of the lower legs, change posture regularly, do exercises for feet regularly, and book

Walk regularly every 60–90 min, and drink a sufficient amount of fluids (at least 150–200 ml every 2 h) which is especially important for people at increased risk of thrombosis. In these passengers well-fitted elastic compression stockings until the knee are recommended and in high-risk passengers additionally the subcutaneous

It is estimated that there is 1 pregnant woman per 1000 air travelers. Reliable data on the incidence of VTE in pregnant women with long-haul flights are so far not available. Considering an approximately fivefold increased risk of VTE during pregnancy (compared to nonpregnant women), various calculation models by Cannegieter and Rosendaal have shown an estimated incidence of venous thrombosis of 0.03–0.1% after one air travel in pregnancy. According to a cohort study including a small number of cases (26 thrombosis, 3 of them are pregnant women), the OR for DVT with air travel and pregnancy was 14.3 (95% CI, 1.7–121.0), corresponding to an

Overall, the absolute risk of VTE during pregnancy is 1–2/1000 pregnancies. This risk increases by fivefold in the puerperium. 20.4% of VTE manifest in the first, 20.9% in the second, and 58.7% in the third trimester; 95% of all postnatal VTE occur within 6 weeks postpartum. The risk of VTE in the puerperium is 20–80 times higher than that in nonpregnant women. Due to the increased production of coagulation factors and a reduction in fibrinolytic activity, hypercoagulability occurs in physiological pregnancy. Healthy pregnant women compensate this hypercoagulable state by pregnancy-induced hemodilution and the increased perfusion in microcirculation. According to the risk classification for VTE by Andersen and Spencer, pregnancy and the puerperium were considered as moderate risk for VTE

(OR between 2 and 9), even in connection with long-haul flights [2, 23–25].

According to RCOG Guideline No. 37a 2015, air travel of more than 4 hours is an independent risk factor for VTE (evidence level III). This risk increases with additional individual risk factors for VTE which have to be considered in the consulting practice (overview at risk factors for VTE associated with air travel). Regardless of pregnancy, the following "thrombogenic" factors were discussed in connection with

Long-term immobilization with sitting for hours in a "cramped" posture (especially kinking of the legs and pressure of the edge of the seat on the popliteal veins) may promote venous stasis in the lower extremities. Air travelers over 190 cm and under 160 cm height are particularly at risk. In this context, it should be mentioned that sitting by the window is associated with a twofold higher risk of VTE than sitting at the aisle. In passengers, with a BMI over 30, the risk of VTE is increased even by sixfold. Significant differences regarding the risk of thrombosis (measurement of the D-dimers) between the first/business class and the economy class have not

yet been demonstrated; however, related data are limited [26–29].

#### *Vein Thrombosis Risk in Women and Travel DOI: http://dx.doi.org/10.5772/intechopen.92229*

*Tourism*

of deep vein thrombosis.

*3.2.2 Moisture content*

*3.2.4 Cosmic radiation*

higher than on the ground.

**3.3 Motion sickness**

**4. Recommendations**

0.005–0.008 mSv/h have been determined.

contraindicated.

*3.2.3 Ozone*

40–70%) in conjunction with other factors such as reduced drinking volume, excessive sweating, or increased diuresis due to increased alcohol/coffee consumption can promote the development of dehydration, respiratory diseases, and finally

It is low in cabin <20% and can cause skin dryness and eye and nose discomfort. Moisturizing lotion and sunscreen are recommended, whereas contact lenses are

It is a form of oxygen with a different structure to its molecule located in the upper layers of the atmosphere and can irritate the upper respiratory system, but

There are no special effects for passengers on board of the flight. The total effective dose from natural radiation exposure in Germany averages 2.1 millisievert (mSv)/year. The International Commission on Radiological Protection recommends exposure of 1 mSv/year and 0.5 mSv/month as a guideline, within which there is no detectable risk of radiation damage. Internationally, radiation exposure during pregnancy of 1 mSv should not be exceeded totally, which is significantly lower than that associated with a potential health hazard (>20 mSv). The radiation exposure during air travel is clearly dependent on the route, altitude, and duration of the flight. The cosmic radiation in an altitude of 9–12 km is about 100 times

For short-haul flights (lower flight altitudes), a radiation exposure of on average 0.001–0.003 mSv/h and for long-haul flights (higher altitude, other flight route) of

It does not occur regularly except in case of atmospheric disturbances. If predis-

Nearly 50% of the passengers with DVT of one or more extremities may be asymptomatic. However, edema of the limb, pain, and signs as red and hot to touch skin are some of the symptoms. Unspecific symptoms of pulmonary embolism may be present, such as unexplained dyspnea, abnormal heart rhythm, chest pain, intolerance that may be aggravated by coughing or deep inhalation, coughing up blood, anxiety, dizziness, or a tendency to faint. Especially, people in high-risk groups should be informed about early recognition of these symptoms in order to seek for medical help. Preventive measures include sufficient hydration, avoidance

posed it is prudent to avoid alcohol and to supply appropriate medicines.

of alcohol/excessive caffeine intake, and regular walking during the trip.

The risk of VTE is eightfold increased in patients with the factor V Leiden mutation that affects blood clotting. These passengers should be considered for heparin prophylaxis. According to the French Society of Cardiology, the probability

eyes and nose are decomposed by heat and eliminated by compressors.

**156**

of venous thrombosis during an airline flight is multiplied by 2.81 in a healthy person, regardless of flight time. The risk is then increased by 26% for every 2 h of flight. Before traveling it is prudent to take the following recommendations into consideration:

Wear comfortable clothing, leave space under the front seat to allow mobility of the lower legs, change posture regularly, do exercises for feet regularly, and book aisle seat, if you are predisposed to VTE.

Walk regularly every 60–90 min, and drink a sufficient amount of fluids (at least 150–200 ml every 2 h) which is especially important for people at increased risk of thrombosis. In these passengers well-fitted elastic compression stockings until the knee are recommended and in high-risk passengers additionally the subcutaneous administration of low molecular weight heparin 2–6 h before traveling.

## **4.1 Pregnancy and travel**

It is estimated that there is 1 pregnant woman per 1000 air travelers. Reliable data on the incidence of VTE in pregnant women with long-haul flights are so far not available. Considering an approximately fivefold increased risk of VTE during pregnancy (compared to nonpregnant women), various calculation models by Cannegieter and Rosendaal have shown an estimated incidence of venous thrombosis of 0.03–0.1% after one air travel in pregnancy. According to a cohort study including a small number of cases (26 thrombosis, 3 of them are pregnant women), the OR for DVT with air travel and pregnancy was 14.3 (95% CI, 1.7–121.0), corresponding to an estimated absolute risk of 1/109 flights [2, 23–25].

Overall, the absolute risk of VTE during pregnancy is 1–2/1000 pregnancies. This risk increases by fivefold in the puerperium. 20.4% of VTE manifest in the first, 20.9% in the second, and 58.7% in the third trimester; 95% of all postnatal VTE occur within 6 weeks postpartum. The risk of VTE in the puerperium is 20–80 times higher than that in nonpregnant women. Due to the increased production of coagulation factors and a reduction in fibrinolytic activity, hypercoagulability occurs in physiological pregnancy. Healthy pregnant women compensate this hypercoagulable state by pregnancy-induced hemodilution and the increased perfusion in microcirculation. According to the risk classification for VTE by Andersen and Spencer, pregnancy and the puerperium were considered as moderate risk for VTE (OR between 2 and 9), even in connection with long-haul flights [2, 23–25].

According to RCOG Guideline No. 37a 2015, air travel of more than 4 hours is an independent risk factor for VTE (evidence level III). This risk increases with additional individual risk factors for VTE which have to be considered in the consulting practice (overview at risk factors for VTE associated with air travel). Regardless of pregnancy, the following "thrombogenic" factors were discussed in connection with long-haul flights.

### **4.2 Immobilization**

Long-term immobilization with sitting for hours in a "cramped" posture (especially kinking of the legs and pressure of the edge of the seat on the popliteal veins) may promote venous stasis in the lower extremities. Air travelers over 190 cm and under 160 cm height are particularly at risk. In this context, it should be mentioned that sitting by the window is associated with a twofold higher risk of VTE than sitting at the aisle. In passengers, with a BMI over 30, the risk of VTE is increased even by sixfold. Significant differences regarding the risk of thrombosis (measurement of the D-dimers) between the first/business class and the economy class have not yet been demonstrated; however, related data are limited [26–29].

Other risk factors associated with air travel are dehydration, reduced air pressure and humidity in the aircraft cabin, disruption of circadian rhythm and hypobaric hypoxia and their effects on changes in the coagulation system [30, 31].

#### **4.3 Recommendations for prevention**

So far there are no evidence-based recommendations for the prevention of VTE during air travel, but there are some based on expert consensus (mostly grade D) in various international guidelines. Only the RCOG Scientific Impact Paper No. 1 from 2013 and the ACOG Committee Opinion No. 443 of 2009 explicitly address air travel and pregnancy. A decisive prerequisite for adequate prevention (especially for pregnant women) is a careful individual assessment of risk factors by the doctor (gynecologist/family doctor) before starting the flight. This provides the basis for risk-adapted thromboembolism prophylaxis. A total of five guidelines make riskrelated recommendations including risk classification for VTE after air travel [26–29].

According to the AWMF guideline 003/001 (S3), long air flights or bus trips do not require any special prophylaxis measures apart from general basic measures; in individual cases when there are risk factors, calf-length compression stockings should be considered.

If the risk is low, general measures are enough. With intermediate risk, e.g., pregnancy/puerperium, in addition to the general measures from a flight duration of 4 h, the wearing of graduated compression stockings up to the knee is recommended. The importance of compression stockings for thrombosis prophylaxis on long-haul flights (>4 h) also emerges from a 2006 Cochrane analysis (revised 2010) including 10 randomized trials [26–33].

The scientific studies (n = 2856) with moderate quality and different risk profiles for VTE were considered. The primary outcome criterion of this analysis was the rate of symptomatic and asymptomatic (diagnosed by sonography or phlebography) deep vein thrombosis. Wearing well-fitted compression stockings has shown to reduce the rate of asymptomatic deep vein thrombosis from 3.6 to 0.2% (OR 0.10; 95% CI 0.04–0.25; p < 0.00001); in addition, the frequency of leg edema was also significantly shown to be significantly decreased as reported by the LONFLIT-4 study [26–35].

If there is a high risk of VTE, in addition to compression stockings, the prophylactic subcutaneous administration of low-molecular heparin (LMH) after individual risk assessment should be considered; aspirin is not indicated in these cases [26–33].

## **5. General contraindications for air travel of pregnant women**

Severe anemia <7.5 g/dl; otitis media and sinusitis; severe heart and lung diseases; recent gastrointestinal surgery, including laparoscopic surgery; bone fractures; risk of leg swelling, especially in the first few days after wearing one plaster cast; referred fear of flying are contraindications for air traveling [26–35].

#### **5.1 Absolute and relative obstetric contraindications**

It goes without saying that unclear symptoms such as bleeding, abdomen pain, gastrointestinal symptoms, or clinical signs of preeclampsia or thrombosis must be clarified before traveling, especially since most airlines issues demand a medical certificate about the safety air of travel. The 2nd trimester, especially the interval between the 18th and 24th week of gestation, is considered the safest time to travel because the risk of obstetric complications (e.g., premature labor) is lowest at this

**159**

*Vein Thrombosis Risk in Women and Travel DOI: http://dx.doi.org/10.5772/intechopen.92229*

the medical/obstetric (emergency) care on site [26–35].

"Preeclampsia" (previous/current pregnancy).

"Previous abortions/ectopic pregnancy".

decreases from 97 to 99% to 90–94% [36–41].

"Placenta previa, placental disorders" [26–35].

**6.1 General effects of travel in pregnant women's health**

The association between air travel and pregnancy outcome concerning early or late pregnancy loss, incidence of malformations placenta abruption, etc. is very limited. The average altitude for commercial long-haul flights is 10,000–12,500 m. The air pressure drops from 760 mmHg (at sea level) to 560 mmHg at flight level. This drop-in air pressure is largely compensated for by the cabin pressure in the aircraft (equivalence to an altitude of 1524–2438 m above sea level) so that an altitude of about 12,200 m is tolerated by the passengers without hypoxic stress. The partial pressure of oxygen in the arterial blood depends on the lung function (cave: chronic obstructive pulmonary diseases); in healthy passengers it drops from 95 mmHg to 53–78 mmHg in the airplane, and the arterial oxygen saturation

For healthy pregnant women who have sufficient oxygen saturation, this "relative" hypoxia in the plane poses no significant risk even for a healthy fetus. No influence on the fetal heart rate during short-haul flights was observed [30, 31, 42]. Due to the approximately 50% higher hemoglobin concentration compared to the

*5.1.1 Absolute contraindications*

"Vaginal bleeding". "Impending abortion".

*5.1.2 Relative contraindications*

"Multiple pregnancy".

**6. Discussion**

"Abnormal child growth".

"Maternal age <15 or >35 years".

"Suspected ectopic pregnancy".

time. In the third trimester, pregnancy risks, such as preeclampsia, intrauterine growth restriction, antenatal bleeding due to placenta previa, severe anemia, and the increased risk of premature birth (previous preterm birth, recurrent premature labor, and cervical insufficiency), should be excluded prior to the flight. Most airlines allow pregnant women with uncomplicated single pregnancy to travel up to (and including) 36th week of pregnancy and women with uncomplicated multiple-child pregnancy up to 32nd week of pregnancy, which is in accordance with the regulations of the International Air Travel Association. As shown in previous studies, there are still no uniform regulations for the transportation of pregnant passengers in civil aviation. It is therefore advisable to check the relevant conditions of carriage of the different airlines on their website before each flight; this also applies to the certification obligations. In addition, information about the destination/place of residence should be obtained before starting the flight, in particular about the climate, altitude, humidity, risk of infection, etc., and about

"Premature placental abruption" due to manifestation of contractions. "Cervical insufficiency" premature labor, premature bladder jump.

*Vein Thrombosis Risk in Women and Travel DOI: http://dx.doi.org/10.5772/intechopen.92229*

*Tourism*

Other risk factors associated with air travel are dehydration, reduced air pressure and humidity in the aircraft cabin, disruption of circadian rhythm and hypobaric

So far there are no evidence-based recommendations for the prevention of VTE during air travel, but there are some based on expert consensus (mostly grade D) in various international guidelines. Only the RCOG Scientific Impact Paper No. 1 from 2013 and the ACOG Committee Opinion No. 443 of 2009 explicitly address air travel and pregnancy. A decisive prerequisite for adequate prevention (especially for pregnant women) is a careful individual assessment of risk factors by the doctor (gynecologist/family doctor) before starting the flight. This provides the basis for risk-adapted thromboembolism prophylaxis. A total of five guidelines make riskrelated recommendations including risk classification for VTE after air travel [26–29]. According to the AWMF guideline 003/001 (S3), long air flights or bus trips do not require any special prophylaxis measures apart from general basic measures; in individual cases when there are risk factors, calf-length compression stockings

If the risk is low, general measures are enough. With intermediate risk, e.g., pregnancy/puerperium, in addition to the general measures from a flight duration of 4 h, the wearing of graduated compression stockings up to the knee is recommended. The importance of compression stockings for thrombosis prophylaxis on long-haul flights (>4 h) also emerges from a 2006 Cochrane analysis (revised 2010)

The scientific studies (n = 2856) with moderate quality and different risk profiles for VTE were considered. The primary outcome criterion of this analysis was the rate of symptomatic and asymptomatic (diagnosed by sonography or phlebography) deep vein thrombosis. Wearing well-fitted compression stockings has shown to reduce the rate of asymptomatic deep vein thrombosis from 3.6 to 0.2% (OR 0.10; 95% CI 0.04–0.25; p < 0.00001); in addition, the frequency of leg edema was also significantly shown to be significantly decreased as reported by the LONFLIT-4

If there is a high risk of VTE, in addition to compression stockings, the prophylactic subcutaneous administration of low-molecular heparin (LMH) after individual risk assessment should be considered; aspirin is not indicated in these cases [26–33].

Severe anemia <7.5 g/dl; otitis media and sinusitis; severe heart and lung diseases; recent gastrointestinal surgery, including laparoscopic surgery; bone fractures; risk of leg swelling, especially in the first few days after wearing one plaster cast; referred

It goes without saying that unclear symptoms such as bleeding, abdomen pain, gastrointestinal symptoms, or clinical signs of preeclampsia or thrombosis must be clarified before traveling, especially since most airlines issues demand a medical certificate about the safety air of travel. The 2nd trimester, especially the interval between the 18th and 24th week of gestation, is considered the safest time to travel because the risk of obstetric complications (e.g., premature labor) is lowest at this

**5. General contraindications for air travel of pregnant women**

fear of flying are contraindications for air traveling [26–35].

**5.1 Absolute and relative obstetric contraindications**

hypoxia and their effects on changes in the coagulation system [30, 31].

**4.3 Recommendations for prevention**

including 10 randomized trials [26–33].

should be considered.

study [26–35].

**158**

time. In the third trimester, pregnancy risks, such as preeclampsia, intrauterine growth restriction, antenatal bleeding due to placenta previa, severe anemia, and the increased risk of premature birth (previous preterm birth, recurrent premature labor, and cervical insufficiency), should be excluded prior to the flight. Most airlines allow pregnant women with uncomplicated single pregnancy to travel up to (and including) 36th week of pregnancy and women with uncomplicated multiple-child pregnancy up to 32nd week of pregnancy, which is in accordance with the regulations of the International Air Travel Association. As shown in previous studies, there are still no uniform regulations for the transportation of pregnant passengers in civil aviation. It is therefore advisable to check the relevant conditions of carriage of the different airlines on their website before each flight; this also applies to the certification obligations. In addition, information about the destination/place of residence should be obtained before starting the flight, in particular about the climate, altitude, humidity, risk of infection, etc., and about the medical/obstetric (emergency) care on site [26–35].
