Table 2.

Increased Risk of Thrombosis in Persons with the Factor V Leiden Variant and Additional Acquired Risk Factors

Risk FactorRisk for VTECommentCitation
Malignancy 1 HR 1.64
(95% CI 1.48-1.80)		Risk varies according to type of cancer; incl persons w/factor V Leiden &/or F2 G20210A variant Shi et al [2023]
CVC use RR 2.7
(95% CI 1.9-3.8)		Incl persons w/factor V Leiden or F2 G20210A variant Van Rooden et al [2004]
OR 4.6
(95% CI 2.6-8.1)		Meta-analysis involving 1,000 affected persons Dentali et al [2008]
Travel OR 8.1
(95% CI 2.7-24.7)		Risk ↑ w/travel duration; travel by car, bus, or train led to high RR of thrombosis. Cannegieter et al [2006]
Normal weight w/:
  • O blood group: OR 5.6
    (95% CI 2.4-12.9)
  • Non-O blood group: OR 16.3
    (95% CI 7.5-35.4)
Overweight/obese persons w/factor V Leiden & non-O blood had highest risk of thrombosis when travel coexisted as risk factor. Ribeiro et al [2016]
Overweight w/:
  • O blood group: OR 13.6
    (95% CI 3.1-60.9)
  • Non-O blood group: OR 21.7
    (95% CI 10.0-47.1)
Obesity w/:
  • O blood group: OR 9.2
    (95% CI 2.0-42.2)
  • Non-O blood group: OR 37.5
    (95% CI 10.5-133)
COCs 1 OR 20.6
(95% CI 8.9-58)		COCs are assoc w/higher risk of VTE than progestin-only contraception in those w/factor V Leiden variant Bergendal et al [2014]
RR 6.14
(95% CI 2.58-14.46)		 van Vlijmen et al [2016]
  • ≤1 yr COC use: OR 62.2
    (95% CI 29.8-129.6)
  • >1 yr COC use: OR 25.4
    (95% CI 16.5-39.2)
After 1st year of COC use RR ↓ but remained high (data incl those w/factor V Leiden or F2 20210G>A variant) Martinelli et al [2016]
OR 19.3
(95% CI 13.9-26.8)		Risk by progestogen type in COC:
  • Gestodene: OR 22.1
    (95% CI 11.3-43.3)
  • Desogestrel: OR 26.3
    (95% CI 15.2-45.5)
  • Levonorgestrel: OR 17.4
    (95% CI 11.4-26.6)
  • Cyproterone: OR 31.8
    (95% CI 17.2-59.0)
 Khialani et al [2020]
  • ≤2 yrs COC use: HR 5.73
    (95% CI 5.31-6.17)
  • >2 yrs COC use: HR 2
    (95% CI 1.86-2.16)
Highest risk of VTE in 1st 2 yrs of use; from study of 240,000 women in UK Biobank Lo Faro et al [2024]
Progestogen-only contraception OR 5.4
(95% CI 2.5-13)		 Bergendal et al [2014]
Oral HRT 1 OR 16.4
(95% CI 4.3-62.2)		Postmenopausal women Straczek et al [2005]
OR 17.1
(95% CI 3.7-78)		Estrogen-progestin HRT Douketis et al [2011]
OR 6.69
(95% CI 3.09-14.49)		 Cushman et al [2004]
Transdermal HRT 1 OR 4.6
(95% CI 1.6-13.8)		Transdermal estrogen Straczek et al [2005]
Obesity (BMI >30 kg/m2) HR 5.27
(95% CI 2.74-10.14)		Risk ↑ w/BMI Severinsen et al [2010]
  • O blood group: OR 5.6
    (95% CI 3.0-10.4)
  • Non-O blood group: OR 15.7
    (95% CI 9.4-25.9)
Greater risk in those w/non-O blood Ribeiro et al [2016]
Overweight (BMI >25 to <30 kg/m2) HR 3.60
(95% CI 2.31-5.63)		Risk ↑ w/BMI Severinsen et al [2010]
  • O blood group: OR 4.4
    (95% CI 2.9-6.6)
  • Non-O blood group: OR 10.7
    (95% CI 7.7-14.8)
Greater risk in those w/non-O blood Ribeiro et al [2016]
Organ transplantation No significant association↑ risk of hepatic arterial thrombosis in liver transplantation has been reported.Ghisdal et al [2010], Pereboom et al [2011], Parajuli et al [2016]
Minor leg injury OR 49.7
(95% CI 6.8-362.7)		Minor injury in previous 3 mos van Stralen et al [2008]
OR 11.0
(95% CI 2.5-48.0)		Below-knee cast immobilization van Adrichem et al [2014]
Surgery Likely ↑ riskMajor orthopedic surgeryJoseph et al [2005], Charen et al [2015]
>15-fold ↑Arthroscopy of knee van Adrichem et al [2015]
Age 17.1%
(95% CI 11.4%-21.4%)		Lifetime risk in heterozygotes & homozygotes for factor V Leiden variant Bell et al [2016]
Age >70 yrs OR 2.2
(95% CI 1.2-3.9)		 Karasu et al [2016]
Age <40 years + nonsmoker + BMI <25 kg/m2 0.7% in heterozygotes
(95% CI 0.5%-1%)		Lowest 10-yr absolute risk of VTE is in those of younger age, nonsmokers, & lower BMI Juul et al [2004]
3% in homozygotes
(95% CI 1%-8%)
Age >60 years + smoker + BMI >30 kg/m2 10% in heterozygotes
(95% CI 7%-14%)		Highest 10-yr absolute risk of VTE is in those of older age, smokers, & ↑ BMI
51% in homozygotes
(95% CI 13%-100%)

BMI = body mass index; COCs = combined oral contraceptives; CVC = central venous catheter; HR = hazard ratio; HRT = hormone replacement therapy; OR = odds ratio; RR = relative risk; VTE = venous thromboembolism

1.

See text that follows table for more details.

From: Factor V Leiden Thrombophilia

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