This is the current release of the guideline.

This guideline updates a previous version: Bates SM, Greer IA, Hirsh J, Ginsberg JS. Use of antithrombotic agents during pregnancy: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004 Sep;126(3 Suppl):627S-44S.

The grades of recommendation (1A, 1B, 1C, 2A, 2B, 2C) are defined at the end of the "Major Recommendations" field.

Fetal Complications of Anticoagulant Therapy during Pregnancy

Vitamin K Antagonists (VKA) Exposure in Utero

1. For women receiving anticoagulation for the management of venous thromboembolism (VTE) who become pregnant, the guideline developers recommend that VKAs be substituted with unfractionated heparin (UFH) or low-molecular weight heparin (LMWH) (Grade 1A).
2. For women with mechanical valves who become pregnant, the guideline developers suggest either adjusted-dose twice a day (bid) LMWH or UFH throughout pregnancy or adjusted-dose bid LMWH or UFH until the thirteenth week with substitution by VKAs until LMWH or UFH are resumed close to delivery (Grade 1C). In pregnant women with high-risk mechanical valves (e.g., older-generation valve in the mitral position or history of thromboembolism), the guideline developers suggest the use of oral anticoagulants over heparin (Grade 2C).

   Underlying values and preferences: The suggestion to utilize VKAs during the first 12 weeks of pregnancy places similar value on avoiding maternal thromboembolic complications as on avoiding fetal risks.

Management of Women Receiving Long-term VKAs Who Are Considering Pregnancy

For women requiring long-term VKAs who are attempting pregnancy and are candidates for UFH or LMWH substitution, the guideline developers suggest performing frequent pregnancy tests and substituting UFH or LMWH for VKAs when pregnancy is achieved (Grade 2C).

Underlying values and preferences: This recommendation places a higher value on avoiding the risks, inconvenience, and costs of UFH or LMWH therapy of uncertain duration while awaiting pregnancy compared to minimizing the risks of early miscarriage associated with VKA therapy.

Use of Anticoagulants in Nursing Women

1. For lactating women using warfarin or UFH who wish to breastfeed, the guideline developers recommend continuing these medications (Grade 1A).
2. For lactating women using LMWH, danaparoid, or r-hirudin who wish to breastfeed, the guideline developers suggest continuing these medications (Grade 2C).
3. For breastfeeding women, the guideline developers suggest alternative anticoagulants rather than pentasaccharides (Grade 2C).

Maternal Complications of Anticoagulant Therapy

LMWH Therapy

For pregnant patients, the guideline developers suggest LMWH over UFH for the prevention and treatment of VTE (Grade 2C).

VTE Following Cesarean Section

Risk of VTE Following Cesarean Section

1. The guideline developers suggest that a thrombosis risk assessment be carried out in all women undergoing cesarean section to determine the need for thromboprophylaxis (Grade 2C).
2. In patients without additional thrombosis risk factors undergoing cesarean section, the guideline developers recommend against the use of specific thromboprophylaxis other than early mobilization (Grade 1B).

Thromboprophylaxis Following Cesarean Section

1. For women considered at increased risk of VTE after cesarean section because of the presence of at least one risk factor in addition to pregnancy and cesarean section, the guideline developers suggest pharmacologic thromboprophylaxis (prophylactic LMWH or UFH) or mechanical prophylaxis (graduated compression stockings or intermittent pneumatic compression) while in hospital following delivery (Grade 2C).
2. For women with multiple additional risk factors for thromboembolism who are undergoing cesarean section and are considered to be at very high risk of VTE, the guideline developers suggest that pharmacologic prophylaxis be combined with the use of graduated compression stockings and/or intermittent pneumatic compression (Grade 2C).
3. For selected high-risk patients in whom significant risk factors persist following delivery, the guideline developers suggest extended prophylaxis (up to 4 to 6 weeks after delivery) following discharge from the hospital (Grade 2C).

VTE during Pregnancy

Treatment of VTE during Pregnancy

1. For pregnant women with acute VTE, the guideline developers recommend initial therapy with either adjusted-dose subcutaneous (SC) LMWH or adjusted-dose UFH (IV bolus, followed by a continuous infusion to maintain the activated partial thromboplastin time (aPTT) within the therapeutic range or subcutaneous therapy adjusted to maintain the APTT 6 hours after injection into the therapeutic APTT range) for at least 5 days (Grade 1A).
2. For pregnant women with acute VTE, after initial therapy, the guideline developers recommend that subcutaneous LMWH or UFH should be continued throughout pregnancy (Grade 1B).
3. For pregnant women with acute VTE, the guideline developers suggest that anticoagulants should be continued for at least 6 weeks postpartum (for a minimum total duration of therapy of 6 months) (Grade 2C).
4. For pregnant women receiving adjusted-dose LMWH or UFH therapy, the guideline developers recommend discontinuation of the heparin at least 24 hours prior to elective induction of labor (Grade 1C).

Prevention of VTE in Pregnant Women With Prior Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE)

Prevention of Recurrent VTE in Pregnant Women

1. For pregnant women with a single episode of VTE associated with a transient risk factor that is no longer present and no thrombophilia, the guideline developers recommend clinical surveillance antepartum and anticoagulant prophylaxis postpartum (Grade 1C).
2. If the transient risk factor associated with a previous VTE event is pregnancy or estrogen related, the guideline developers suggest antepartum clinical surveillance or prophylaxis (prophylactic LMWH/UFH or intermediate-dose LMWH/UFH) plus postpartum prophylaxis, rather than routine care (Grade 2C).
3. For pregnant women with a single idiopathic episode of VTE but without thrombophilia and who are not receiving long-term anticoagulants, the guideline developers recommend one of the following, rather than routine care or adjusted-dose anticoagulation: prophylactic LMWH/UFH or intermediate-dose LMWH/UFH or clinical surveillance throughout pregnancy plus postpartum anticoagulants (Grade 1C).
4. For pregnant women with thrombophilia (confirmed laboratory abnormality) who have had a single prior episode of VTE and are not receiving long-term anticoagulants, the guideline developers recommend one of the following, rather than routine care or adjusted-dose anticoagulation: antepartum prophylactic or intermediate-dose LMWH or prophylactic or intermediate-dose UFH or clinical surveillance throughout pregnancy; plus postpartum anticoagulants (Grade 1C).
5. For women with "higher-risk" thrombophilias (e.g., antithrombin deficiency, persistent positivity for the presence of antiphospholipid antibodies; compound heterozygosity for prothrombin G20210A variant and factor V Leiden or homozygosity for these conditions) who have had a single prior episode of VTE and are not receiving long-term anticoagulants, the guideline developers suggest, in addition to postpartum prophylaxis, antepartum prophylactic or intermediate-dose LMWH or prophylactic or intermediate-dose UFH, rather than clinical surveillance (Grade 2C).
6. For pregnant women with multiple (> 2) episodes of VTE not receiving long-term anticoagulants, the guideline developers suggest antepartum prophylactic, intermediate-dose, or adjusted-dose LMWH or prophylactic, intermediate-dose or adjusted-dose UFH followed by postpartum anticoagulants rather than clinical surveillance (Grade 2C).
7. For pregnant women receiving long-term anticoagulants for prior VTE, the guideline developers recommend LMWH or UFH throughout pregnancy (either adjusted-dose LMWH or UFH, 75% of adjusted-dose LMWH, or intermediate-dose LMWH) followed by resumption of long-term anticoagulants postpartum (Grade 1C).
8. For all pregnant women with previous DVT, the guideline developers suggest the use of graduated elastic compression stockings both antepartum and postpartum (Grade 2C).

   Underlying values and preferences: This recommendation places a high value on uncertain incremental benefit with stockings and a low value on avoiding discomfort and inconvenience.

Prevention of VTE in Pregnant Women with Thrombophilia and No Prior VTE

Risk of Pregnancy-Related VTE in Women with Thrombophilia

For pregnant patients with thrombophilia but no prior VTE, the guideline developers recommend that physicians do not use routine pharmacologic antepartum prophylaxis but instead perform an individualized risk assessment (Grade 1C).

Prevention of Pregnancy-Related VTE in Women with Thrombophilia

1. For pregnant women with no history of VTE but antithrombin deficiency, the guideline developers suggest antepartum and postpartum prophylaxis (Grade 2C).
2. For all other pregnant women with thrombophilia and no prior VTE, the guideline developers suggest antepartum clinical surveillance or prophylactic LMWH or UFH, plus postpartum anticoagulants (Grade 2C).

Thrombophilia and Pregnancy Complications

Risk of Pregnancy Complications in Women with Thrombophilia

1. For women with recurrent early pregnancy loss (three or more miscarriages) or unexplained late pregnancy loss, the guideline developers recommend screening for antiphospholipid antibodies (APLAs) (Grade 1A).
2. For women with severe or recurrent preeclampsia or IUGR, the guideline developers suggest screening for APLAs (Grade 2C).

Prevention of Pregnancy Complications in Women with Thrombophilia

For women with APLAs and recurrent (three or more) pregnancy loss or late pregnancy loss and no history of venous or arterial thrombosis, the guideline developers recommend antepartum administration of prophylactic or intermediate-dose UFH or prophylactic LMWH combined with aspirin (Grade 1B).

Management of Women with a History of Preeclampsia and No Thrombophilia

Prevention of Recurrent Preeclampsia in Women Without Thrombophilia

1. For women considered high risk for preeclampsia, the guideline developers recommend low-dose aspirin therapy throughout pregnancy (Grade 1B).
2. For women with a history of preeclampsia, the guideline developers suggest that UFH and LMWH should not be used as prophylaxis in subsequent pregnancies (Grade 2C).

Maternal and Fetal Risks Related to Anticoagulation During Pregnancy for Mechanical Prosthetic Valves

Anticoagulant Management of Mechanical Prosthetic Valves in Pregnant Women

1. For pregnant women with mechanical heart valves the guideline developers recommend that the decision about anticoagulant management during pregnancy include an assessment of additional risk factors for thromboembolism including valve type, position, and history of thromboembolism and that the decision should also be influenced strongly by patient preferences (Grade 1C).
2. For pregnant women with mechanical heart valves, the guideline developers recommend one of the following anticoagulant regimens in preference to no anticoagulation:
   1. Adjusted-dose bid LMWH throughout pregnancy (Grade 1C). The guideline developers suggest that doses be adjusted to achieve the manufacturer's peak anti-Xa LMWH 4 hours after SC injection (Grade 2C) or
   2. Adjusted-dose UFH throughout pregnancy administered SC every twelve hours (q12h) in doses adjusted to keep the mid-interval aPTT at least twice control or attain an anti-Xa heparin level of 0.35 to 0.70 U/mL (Grade 1C)
   3. UFH or LMWH (as above) until the thirteenth week with warfarin substitution until close to delivery when UFH or LMWH is resumed (Grade 1C).

      In women judged to be at very high risk of thromboembolism in whom concerns exist about the efficacy and safety of UFH or LMWH as dosed above (e.g., older-generation prosthesis in the mitral position or history of thromboembolism), the guideline developers suggest VKAs throughout pregnancy with replacement by UFH or LMWH (as above) close to delivery, rather than one of the regimens above; after a thorough discussion of the potential risks and benefits of this approach (Grade 2C).

      Underlying values and preferences: In contrast to our other recommendations, which place a high value on avoiding fetal risk, the recommendation for women at very high risk of thromboembolism places equal value on avoiding maternal complications.

      Remark: For all the recommendations above, usual long-term anticoagulants should be resumed postpartum.

3. For pregnant women with prosthetic valves at high risk of thromboembolism, the guideline developers recommend the addition of low-dose aspirin, 75 to 100 mg/d (Grade 2C).

Definitions:

*The guideline developers use the wording recommend for strong (Grade 1) recommendations and suggest for weak (Grade 2) recommendations.

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

Not applicable: The guideline was not adapted from another source.

2001 Jan (revised 2008 Jun)

American College of Chest Physicians - Medical Specialty Society

American College of Chest Physicians

American College of Chest Physicians (ACCP) Expert Panel on Antithrombotic and Thrombolytic Therapy

Primary Authors: Shannon M. Bates, MDCM, MSc, Chair; Ian A. Greer, MD; Ingrid Pabinger, MD; Shoshanna Sofaer, DrPh; and Jack Hirsh, CM, MD, FCCP

Committee Co-Chairs: Jack Hirsh, MD, FCCP (Chair); Gordon H. Guyatt, MD, FCCP; Gregory W. Albers, MD; Robert A. Harrington, MD, FCCP; Holger J. Schünemann, MD, PhD, FCCP

Participants: Giancarlo Agnelli, MD; Pierre Amarenco, MD; Jack E. Ansell, MD; Collin Baigent; Shannon M. Bates, MD; Kenneth A. Bauer, MD; Richard C. Becker, MD; Peter B. Berger, MD; David Bergqvist, MD, PhD; Rebecca J. Beyth, MD; Christopher P. Cannon, MD; Elizabeth A. Chalmers, MB, ChB, MD; Anthony K.C. Chan, MBBS; Clifford W. Colwell, Jr., MD; Anthony J. Comerota, MD; Deborah Cook, MD; Mark A. Crowther, MD; James E. Dalen, MD; Gabrielle deVeber, MD, MHSc; Maria Benedetta Donati, MD, PhD; James D. Douketis, MD; Andrew Dunn, MD; J. Donald Easton, MD; Michael Ezekowitz, MD; Margaret Fang; William H. Geerts, MD, FCCP; Alan S. Go, MD; Samuel Z. Goldhaber, MD, FCCP; Shaun D. Goodman, MD; Michael Gould, MD, FCCP; Ian A. Greer, MD; Andreas Greinacher, MD; David Gutterman, MD, FCCP, HSP; Jonathan L. Halperin, MD; John A. Heit, MD; Elaine M. Hylek, MD; Alan Jacobson, MD; Roman Jaeschke, MD, PhD; Amir K. Jaffer, MD; Susan Kahn; Clive Kearon, MBBCh, PhD; Fenella Kirkham, MBBC; Andreas Koster, MD, PhD; Michael R. Lassen, MD; Mark N. Levine, MD, MSc; Sandra Zelman Lewis, PhD; A. Michael Lincoff, MD; Gregory YH Lip, MD; Christopher Madias, MD; Warren J. Manning, MD; Daniel B. Mark, MD; M. Patricia Massicotte, MD, MSc; David Matchar, MD; Thomas W. Meade, DM, FCCP; Venu Menon, MD; Tracy Minichiello, MD; Paul Monagle, MBBS, MSc, MD, FCCP; Christopher M. O'Connor, MD; Patrick O'Gara, MD; E. Magnus Ohman, MD; Ingrid Pabinger, MD; Gualtiero Palareti, MD; Carlo Patrono, MD; Stephen G. Pauker, MD; Graham F. Pineo, MD; Jeffrey J. Popma, MD; Gary Raskob, PhD; Gerald Roth, MD; Ralph L. Sacco, MD; Deeb N. Salem, MD, FCCP; Charles-Marc Samama, MD, FCCP; Meyer Michel Samama, MD; Sam Schulman, MD, PhD; Daniel Singer, MD; Michael Sobel, MD; Shoshanna Sofaer, DrPH; Alex C. Spyropoulos, MD FCCP; Ph. Gabriel Steg, MD; Philip Teal, MD; Raymond Verhaeghe, MD; David A. Vorchheimer, MD; Theodore E. Warkentin, MD; Jeffrey Weitz, MD

Dr. Bates discloses grant monies received from the Canadian Institute of Health Research, the Heart and Stroke Foundation of Ontario, and bioMérieux. She received consultant fees from, and was on advisory committees for, GlaxoSmithKline, Dade Behring, and Trinity Biotech. Dr. Bates also has received an honorarium from LEO Pharma.

Dr. Greer discloses that he has received grant monies from the British Health Foundation and the Chief Scientist's Office (Scotland). He has also received honoraria for lectures for Sanofi-Aventis and Leo, and has served on an advisory committee for Sanofi-Aventis.

Dr. Pabinger discloses that she has received grant monies from CSL Behring and Pfizer. She is also on the speaker bureaus for CSL Behring, Bayer, Pfizer, Aventis, Baxter, and Biotest, and is on advisory committees for Novo, Bayer, and Wyeth. Dr.Pabinger also holds a fiduciary position on the Board of Gesellschaft für Thrombose und Hämostaseforschung.

Dr. Hirsh discloses that he has received partial support for writing two books, one on fondaparinux and one on low-molecular-weight heparin.

Dr. Sofaer reveals no real or potential conflicts of interest or commitment.

American College of Clinical Pharmacy - Medical Specialty Society
American Society of Health-System Pharmacists - Professional Association

This is the current release of the guideline.

This guideline updates a previous version: Bates SM, Greer IA, Hirsh J, Ginsberg JS. Use of antithrombotic agents during pregnancy: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004 Sep;126(3 Suppl):627S-44S.

None available

This summary was completed by ECRI on July 12, 2001. The information was verified by the guideline developer on October 2001. This NGC summary was updated by ECRI on December 9, 2004. The updated information was verified by the guideline developer on January 12, 2005. This summary was updated by ECRI on March 6, 2007 following the U.S. Food and Drug Administration (FDA) advisory on Coumadin (warfarin sodium). This summary was updated by ECRI Institute on June 22, 2007 following the U.S. Food and Drug Administration (FDA) advisory on heparin sodium injection. This summary was updated by ECRI Institute on September 7, 2007 following the revised U.S. Food and Drug Administration (FDA) advisory on Coumadin (warfarin). This summary was updated by ECRI Institute on March 14, 2008 following the updated FDA advisory on heparin sodium injection. This NGC summary was updated by ECRI Institute on December 9, 2008. The updated information was verified by the guideline developer on January 7, 2009.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.