Applied Evidence

Primary prevention of VTE spans a spectrum

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References

Studies suggest that the levonorgestrel-releasing intrauterine device and progestin-only pills are not associated with an increase in VTE risk.27 Although the quality of evidence varies, most nonoral hormonal contraceptives have been determined to carry a risk of VTE that is similar to that of combined oral contraceptives.28

In hormone replacement, avoid pills to lower risk

Hormone replacement therapy (HRT) for postmenopausal women increases VTE risk when administered in oral form, with combined estrogen and progestin HRT doubling the risk and estrogen-only formulations having a lower risk.29 VTE risk is highest in the first 6 months of HRT, declining to that of a non-HRT user within 5 years.29 Neither transdermal HRT nor estrogen creams increase the risk of VTE, according to a systematic review.30 The estradiol-containing vaginal ring also does not confer increased risk.29

Pregnancy, thrombophilia, and VTE prevention

VTE affects as many as 0.2% of pregnancies but causes 9% of pregnancy-related deaths.18 The severity of VTE in pregnancy led the American College of Obstetricians and Gynecologists (ACOG) to recommend primary VTE prophylaxis in patients with certain thrombophilias.18 Thrombophilia testing is recommended in patients with proven high-risk thrombophilia in a first-degree relative.18 ACOG recognizes 5 thrombophilias considered to carry a high risk of VTE in pregnancy18:

  • homozygous Factor V Leiden
  • homozygous prothrombin G20210A mutation
  • antithrombin deficiency
  • heterozygous Factor V Leiden and prothrombin G20210A mutation
  • antiphospholipid antibody syndrome.

ACOG recommends limiting thrombophilia testing to (1) any specific thrombophilia carried by a relative and (2) possibly, the antiphospholipid antibodies anticardiolipin and lupus anticoagulant.18,19 Antiphospholipid testing is recommended when there is a history of stillbirth, 3 early pregnancy losses, or delivery earlier than 34 weeks secondary to preeclampsia.19

Primary VTE prophylaxis is recommended for pregnant patients with a high-risk thrombophilia; low-molecular-weight heparin (LMWH) is safe and its effects are predictable.18 Because postpartum risk of VTE is higher than antepartum risk, postpartum prophylaxis is also recommended with lower-risk thrombophilias18; a vitamin K antagonist or LMWH can be used.18 ACCP and ACOG recommendations for VTE prophylaxis in pregnancy differ slightly (TABLE 316,18,19).

Primary prevention of venous thromboembolism in pregnancy

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