Table 2.

Circumstantial Risk Factors: Increased Risk for Thrombophilia in Persons with the 20210G>A Variant

CircumstanceRelative Risk for VTECommentReference
Pregnancy
  • 3x-15x ↑ risk (heterozygotes)
  • 31x ↑ risk during pregnancy or postpartum
  • 26x ↑ risk (homozygotes)
  • 8-47x ↑ risk in compound heterozygotes (w/factor V Leiden)
Incidence:
  • During pregnancy: 1:200 to 1:300
  • Post partum:1:66 (highest risk: 1st 6 wks post partum)
  • In homozygotes: 1:40
  • In compound heterozygotes (w/factor V Leiden): 1:20 to 1:125
Gerhardt et al [2000], Martinelli et al [2002], Gerhardt et al [2003], Robertson et al [2006], Martinelli et al [2008], Jacobsen et al [2010], Bates et al [2016], Gerhardt et al [2016]
Combined oral
contraceptives 		16x-59x ↑ risk (heterozygotes)
  • Higher risk during 1st yr of use than subsequent yrs
  • Incidence 1/500/yr
  • Unopposed progestin is assoc w/↓ risk for thrombosis vs estrogen-containing contraception.
Martinelli et al [1999b], Bloemenkamp et al [2000], Emmerich et al [2001], Wu et al [2005], Mohllajee et al [2006]
Other
contraceptives
(e.g.,
transdermal,
vaginal ring) 		VTE risk at least as high as risk w/combined oral contraceptives; not specifically studied in women w/20210G>ACole et al [2007], Jick et al [2007], Dore et al [2010]
Oral HRT
  • 3x ↑ risk (heterozygotes) vs women using HRT w/o 20210G>A variant
  • 8x-25x ↑ risk (heterozygotes) vs women w/o 20210G>A variant not using HRT
5x ↑ risk w/conjugated equine estrogen use vs w/esterified estrogenStraczek et al [2005], Smith et al [2006], Canonico et al [2008], Roach et al [2013]
Transdermal
HRT 		Preliminary data suggest may not ↑ risk.Lower relative risk than oral HRTCanonico et al [2010], ACOG [2013a]
SERMS Risk uncertain but likely > risk assoc w/SERMS alone Abramson et al [2006]
Obesity
  • 7x ↑ risk if BMI >30 kg/m2
  • 5x ↑ risk if BMI 25-30 kg/m2
Risk ↑ w/↑ BMI Pomp et al [2007]
Malignancy
  • 17x ↑ risk of VTE
  • 20x ↑ risk of UE VTE
  • 5x ↑ risk of CVC thrombosis
Blom et al [2005a], Blom et al [2005b], Dentali et al [2008b]
Air travel 17x ↑ risk Martinelli et al [2003]
Minor leg
injury 		9x-30x ↑ risk van Stralen et al [2008]
Organ
transplantation 		Data unclearGhisdal et al [2010], Pereboom et al [2011]
CVC Data unclear; CVC is most common risk factor for UE thrombosis in children. Studies evaluating risk in children w/20210G>A were not identified.Studies found no ↑ or 2x-3x ↑ risk.Vayá et al [2003], Van Rooden et al [2004], Linnemann et al [2008]
Surgery Data unclear; any excess risk likely small compared to risk assoc w/surgeryStudies found no ↑ or 10x-13x ↑ risk.Wåhlander et al [2002], Blom et al [2005a], Joseph et al [2005], Ringwald et al [2009]
Antiphospholipid
antibody
syndrome 		Data unclear1 study found 4x ↑ risk (heterozygotes). DeSancho et al [2010]

BMI = body mass index; CVC = central venous catheter; HRT = hormone replacement therapy; SERMS = selective estrogen receptor modulators; UE = upper-extremity; VTE = venous thromboembolism

From: Prothrombin Thrombophilia

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