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Risk of Venous Thromboembolism after Air Travel: Interaction with Thrombophilia and Oral Contraceptives

April 29, 2004

Abstraction Template
     
Key variables & Description Article

Reference
Complete the bibliographic reference for the article according to AJE format.

Martinelli I. , et al. Risk of venous thromboembolism after air travel: interaction with thrombophilia and oral contraceptives. Arch Intern Med. 2003; 163:2771-2774.

Category of HuGE information
Specify the types of information (from the list below) available in the article:

  1. Prevalence of gene variant
  2. Gene-disease association
  3. Gene-environment interaction
  4. Gene-gene interaction
  5. Genetic test evaluation/monitoring
  1. Prevalence of gene variant
  2. Gene-disease association
  3. Gene-environment interaction

 

Study hypotheses or purpose
The authors study hypotheses or main purpose for conducting the study

 

Individuals with inherited thrombophilia and women who use oral contraceptives are at increased risk for VTE after air travel.

 

Gene(s)
Identification of the following:

  • Gene name
  • Chromosome location
  • Gene product/function
  • Alleles
  • OMIM #

Gene name: F5, Factor V
Chromosome location: 1q23
Gene product/function: Coagulation factor 5. A cofactor that participates with factor Xa to activate prothrombin to thrombin.
Alleles: F5, ARG506GLN, 1691-A. Factor V Leiden . Thrombophilia caused by deficiency of cofactor for activated protein C (APC).
OMIM#: 227400

Gene name: F2, Coagulation Factor II.
Chromosome location: 11p11-q12.
Gene product/function: Thrombin. Converts fibrinogen to fibrin adn activates factors V, VII, VIII, XIII, with thrombomodulin and Protein C.
Alleles: F2, 20210G-A. A guanine to adenine transition at position 20210. Increased risk for venous thrombosis caused by elevated levels of prothrombin.
OMIM#: 176930

 

Environmental factor(s)
Identification of the major environmental factors studied (infectious, chemical, physical, nutritional, and behavioral)
  1. Air travel
  2. Oral contraceptive use
  3. Hormone replacement therapy
  4. Pregnancy
  5. Surgery
  6. Trauma
  7. Immobilization

 

Health outcome(s)
Identification of the major health outcome(s) studied
  1. Venous thromboembolism (VTE)
  2. Pulmonary embolism (PE)

Study design
Specification of the type of study design(s)
  1. Case-control
  2. Cohort 
  3. Cross-sectional
  4. Descriptive or case series
  5. Clinical trial
  6. Population screening

 

  1. Case-control Study
Case definition
For study designs 1, 4, and 5, define the following if available:
  1. Disease case definition
  2. Exclusion criteria
  3. Gender
  4. Race/ethnicity
  5. Age
  6. Time period
  7. Geographic location
  8. Number of participants (% of total eligible)
  1. Disease case definition: Patients who attended the Thrombosis Center in Milan, Italy between January 1, 1999 to September 30, 2001 for thrombophilia screening, if they had a first and documented episode of proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in the last 24 months.
  2. (a) Inclusion Criteria: N/A
    (b) Exclusion criteria: Patients younger than 20 years old and over 70 years old, and those with known malignant diseases.
  3. Gender: males (107) and females (103)
  4. Race/ethnicity: N/A
  5. Age: 20-70 years
  6. Time period: N/A
  7. Geographic location: N/A
  8. Number of participants: N ( % of total eligible ) 210

 

Control definition
For study design 1, define the following if available:
  1. Control selection criteria
  2. Matching variables
  3. Exclusion criteria
  4. Gender
  5. Race/ethnicity
  6. Age
  7. Time period
  8. Geographic location
  9. Number of participants (% of total eligible)

 

  1. Control selection criteria: Friends or partners of cases referred to Thrombosis Center who volunteered to be screened for thrombophilia in same trial period of referral as cases.
  2. Matching variables: sex, age, gender, BMI, education (grade school, high school, college, university)
  3. Exclusion criteria: a positive personal history for thrombosis or overt malignant disease
  4. Gender: males (115) and females (95)
  5. Race/ethnicity: N/A
  6. Age: 20-70 years
  7. Time periods: January 1, 1999 to September 30, 2001
  8. Geographic location: N/A
  9. Number of participants: 210
Assessment of environment factors
For studies that include gene-environment interactions, define the following, if available:
  • Environmental factor
  • Exposure assessment
  • Exposure definition
  • Number of participants with exposure data (% of total eligible)

Environmental factors considered for interaction:

  1. Environmental factor: air travel (long [>=8 hrs] and short [<8 hrs] duration
  2. Exposure assessment: self-report
  3. Exposure definition: flew in month preceding the event
  4. Number of participants with exposure: 31 cases (15%) and 16 controls (8%)

Environmental factors considered as potential confounders:

  1. Environmental factor: oral contraceptive use
  2. Exposure assessment: interview
  3. Exposure definition: presence in month preceding event
  4. Number of participants with exposure: 48 cases (61%) and 19 (27%) controls

 

Genotyping
Specify the following:
  • Gene
  • DNA source
  • Methodology
  • Number of participants genotyped (% of total eligible) 
  • Gene: Factor V Leiden
  • DNA source: unspecified
  • Methodology: as described by de Ronde and Bertina
  • Number of participants genotyped: N ( % eligible ) 340 (100%)
  • Gene: Prothrombin G20210A
  • DNA source: unspecified
  • Methodology: as described by Poort et al.
  • Number of participants genotyped: N ( % eligible ) 340 (100%)

 

Results
Describe the major results under each of the following HuGE categories. Include tables when data are provided:
  1. Prevalence of gene variant
  2. Gene-disease association
  3. Gene-environment interaction
  4. Gene-gene interaction
  5. Genetic test evaluation/monitoring

 

  1. Prevalence of Factor V Leiden: 32 cases (15%) and 6 controls (8%)
    Gene-disease association: OR 6.11 (5.22-7.00)
  2. Prevalence of Prothrombin G20210A: 13 cases (6%) and 4 controls (2%)
    Gene-disease association: OR 3.40 (2.26-4.53)
  3. Table 1: Interaction between Air Travel and the Presence of Thrombophilia in Determining Venous Thrombosis
Conclusion
State the author's overall conclusions from the study

Compared with the reference group (who did not fly or have thrombophilia), there was a 6-fold increased risk of VTE in those with thrombophilia, a 2-fold increased risk in those who flew, and a 16-fold increased risk in those with both risk factors. Compared with the reference group (who did not fly or use oral contraceptives), there was a 4-fold increased risk for OC users, a 2-fold increased risk for those who flew, and a 14-fold increased risk for those with both risk factors. Adjusted measures were reportedly did not differ significantly from crude measures.

 

Comments
Provide additional insight, including methodologic issues and/or concerns about the study

The authors mentioned ascertainment bias, in that the cases were asked about transient exposures that had occurred on average 5 months before the interview, and the controls asked about those that occurred in the month preceding month. This may result in some recall bias, but it is difficult to estimate the effect on the odds ratios. Selection bias may also be problematic, as friends and partners of those referred to the Thrombosis Center may be more willing to participate than individuals from a randomized sample of the population.

More information regarding collection of DNA would be helpful.

Last Updated August 14, 2004