This is the current release of the guideline.

This guideline updates a previous version: Ginsberg JS, Greer I, Hirsh J. Use of antithrombotic agents during pregnancy. Chest 2001 Jan;119(1 Suppl):122S-131S.

The rating scheme is defined at the end of the "Major Recommendations" field.

When describing the various regimens of unfractionated heparin (UFH) and low-molecular-weight-heparin (LMWH), the guideline developers use the following terminology:

• Mini-dose UFH: UFH 5,000 U subcutaneous (SC) every 12 hours
• Moderate-dose UFH: UFH SC every 12 hours in doses adjusted to target an anti-Xa level of 0.1 to 0.3 U/mL
• Adjusted-dose UFH: UFH SC every 12 hours in doses adjusted to target a mid-interval activated partial thromboplastin time (aPTT) into the therapeutic range
• Prophylactic LMWH: e.g., dalteparin 5,000 U SC every 24 hours, or enoxaparin 40 mg SC every 24 hours (although at extremes of body weight modification of dose may be required)
• Intermediate-dose LMWH: e.g., dalteparin 5,000 U SC every 12 hours, or enoxaparin 40 mg SC every 12 hours
• Adjusted-dose LMWH: weight-adjusted, full-treatment doses of LMWH administered once or twice daily (e.g., dalteparin 200 U/kg, or tinzaparin 175 U/kg once daily, or dalteparin 100 U/kg every 12 hours, or enoxaparin 1 mg/kg every 12 hours). As the half-life of LMWH is shorter in pregnancy, twice-daily dosing is preferable, at least in the initial treatment phase.
• Postpartum anticoagulants: warfarin for 4 to 6 weeks with a target international normalized ratio (INR) of 2.0 to 3.0, with initial UFH or LMWH overlap until the INR is >2.0
• In addition, the term surveillance refers to clinical vigilance and aggressive investigation of women with symptoms suspicious of deep vein thrombosis (DVT) or pulmonary embolism (PE).

Management of Women Receiving Long-Term Vitamin K Antagonist (VKA) Therapy Who Are Considering Pregnancy

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

Treatment of Venous Thromboembolism (VTE) during Pregnancy

1. In women with acute VTE, the guideline developers recommend either adjusted-dose LMWH throughout pregnancy or intravenous (IV) UFH (bolus followed by a continuous infusion to maintain the aPTT in the therapeutic range) for at least 5 days, followed by adjusted-dose UFH or LMWH for the remainder of the pregnancy. Anticoagulants should be administered for at least 6 weeks postpartum (Grade 1C+).
2. In women receiving adjusted-dose LMWH or UFH therapy, the guideline developers recommend discontinuing the heparin 24 hours prior to elective induction of labor (Grade 1C).

Prevention of VTE during Pregnancy

Prior VTE and Pregnancy

1. In patients with a single episode of VTE associated with a transient risk factor that is no longer present, the guideline developers recommend clinical surveillance and postpartum anticoagulants (Grade 1C). If the previous event is pregnancy or estrogen-related or there are additional risk factors (such as obesity), the guideline developers suggest antenatal anticoagulant prophylaxis (Grade 2C).
2. In patients with a single idiopathic episode of VTE who are not receiving long-term anticoagulants, the guideline developers suggest prophylactic LMWH, or mini-dose UFH, or moderate-dose UFH, or clinical surveillance plus postpartum anticoagulants (Grade 2C).
3. In patients with a single episode of VTE and thrombophilia (confirmed laboratory abnormality) or strong family history of thrombosis and not receiving long-term anticoagulants, the guideline developers suggest prophylactic or intermediate-dose LMWH, or mini-dose or moderate-dose UFH, plus postpartum anticoagulants (Grade 2C).
4. In antithrombin-deficient women, compound heterozygotes for prothrombin G20210A and factor V Leiden and homozygotes for these conditions with a history of VTE, the guideline developers suggest intermediate-dose LMWH prophylaxis or moderate-dose UFH (Grade 2C).
5. In patients with multiple (two or more) episodes of VTE and/or women receiving long-term anticoagulants (e.g., single episode of VTE—either idiopathic or associated with thrombophilia) the guideline developers suggest adjusted-dose UFH or adjusted-dose LMWH followed by resumption of long-term anticoagulants postpartum (Grade 2C).
6. In all women with previous DVT, antenatally and postpartum, the guideline developers suggest use of graduated elastic compression stockings (Grade 2C).

Thrombophilia and VTE Associated with Pregnancy

1. In antithrombin-deficient women, compound heterozygotes for prothrombin G20210A and factor V Leiden, and homozygotes for these conditions with no prior VTE, the guideline developers suggest active prophylaxis (Grade 2C).
2. In all other patients with no prior VTE and thrombophilia (confirmed laboratory abnormality), the guideline developers suggest surveillance or prophylactic LMWH or mini-dose UFH, plus postpartum anticoagulants (Grade 2C).

Thrombophilia and Pregnancy Complications

1. For women with recurrent pregnancy loss (three or more miscarriages) and women with prior severe or recurrent preeclampsia, abruptions, or otherwise unexplained intrauterine death, the guideline developers suggest screening for congenital thrombophilia and antiphospholipid antibodies (APLAs) (Grade 2C).
2. For pregnant patients with APLAs and a history of multiple (two or more) early pregnancy losses or one or more late pregnancy losses, preeclampsia, intrauterine growth retardation (IUGR), or abruption, the guideline developers suggest administration of antepartum aspirin plus mini-dose or moderate-dose UFH or prophylactic LMWH (Grade 2B).
3. For women who are homozygous for thermolabile variant (C677T) or MTHFR, the guideline developers suggest folic acid supplements prior to conception or, if already pregnant, as soon as possible, and throughout pregnancy (Grade 2C).
4. For women with a congenital thrombophilic deficit and recurrent miscarriages, a second-trimester or later loss, severe or recurrent preeclampsia, or abruption, the guideline developers suggest low-dose aspirin therapy plus either mini-dose heparin or prophylactic LMWH therapy (Grade 2C). The guideline developers also suggest that postpartum anticoagulants be administered to these women (Grade 2C).
5. Patients with APLAs and a history of venous thrombosis are usually receiving long-term oral anticoagulation therapy because of the high risk of recurrence. During pregnancy, the guideline developers recommend adjusted-dose LMWH or UFH therapy plus low-dose aspirin and resumption of long-term oral anticoagulation therapy postpartum (Grade 1C).
6. Patients with APLAs and no prior VTE or pregnancy loss should be considered to have an increased risk for the development of venous thrombosis and, perhaps, pregnancy loss. The guideline developers suggest one of the following approaches for these women: surveillance, mini-dose heparin, prophylactic LMWH, and/or low-dose aspirin, 75 to 162 mg daily (all Grade 2C).

Prophylaxis in Patients with Mechanical Heart Valves

In women with prosthetic heart valves, the guideline developers recommend:

1. Adjusted-dose, twice-daily LMWH throughout pregnancy in doses adjusted either to keep a 4-hour postinjection anti-Xa heparin level at approximately 1.0 to 1.2 U/mL (preferable) or according to weight (Grade 1C), or
2. Aggressive adjusted-dose UFH throughout pregnancy: i.e., administered SC every 12 hours in doses adjusted to keep the mid-interval aPTT at least twice control or to attain an anti-Xa heparin level of 0.35 to 0.70 U/mL (Grade 1C), or
3. UFH or LMWH (as above) until the thirteenth week, change to warfarin until the middle of the third trimester, and then restart UFH or LMWH (Grade 1C).

   Remark: Long-term anticoagulants should be resumed postpartum with all regimens.

4. In women with prosthetic heart valves at high risk, the guideline developers suggest the addition of low-dose aspirin, 75 to 162 mg/day (Grade 2C).

Definitions

*These situations include RCTs with both lack of blinding and subjective outcomes, where the risk of bias in measurement of outcomes is high, or RCTs with large loss to follow-up.

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 2004 Sep)

American College of Chest Physicians - Medical Specialty Society

Funding was provided through an unrestricted educational grant by AstraZeneca LP, Aventis Pharmaceuticals, GlaxoSmithKline, Bristol-Myer Squibb/Sanofi-Synthelabo Partnership, and Organon Sanofi-Synthelabo LLC.

American College of Chest Physicians Consensus Panel on Antithrombotic and Thrombolytic Therapy

Primary Authors: Jeffrey S. Ginsberg, MD, FRCPC (Chair); Shannon M. Bates, MDCM, FRCPC; Ian A. Greer, MD, FRCP (Glas Edin London), FRCOG; Jack Hirsh, MD, FCCP

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

Participants: Giancarlo Agnelli, MD; Amin Al-Ahmad, MD; Pierre Amarenco, MD; Jack E. Ansell, MD; Shannon M. Bates, MD; Richard C. Becker, MD; Peter B. Berger, MD; David Bergqvist, MD, PhD, FRCS; Rebecca J. Beyth, MD, MSc; Stewart Brower, MLIS; Harry R. Buller, MD; Henry I. Bussey, PharmD, FCCP; Christopher P. Cannon, MD, FACC; Elizabeth A. Chalmers, MB, ChB, MD, MRCP(UK). FRCPath; Anthony K.C. Chan, MD; G. Patrick Clagett, MD; Barry Coller, MD; Clifford W. Colwell, MD; Deborah Cook, MD, MSc; James E. Dalen, MD, MPH, FCCP; J. Donald Easton, MD; Michael Ezekowitz, MD; Garret A. Fitzgerald, MD; William H. Geerts, MD, FCCP; Jeffrey S. Ginsberg, MD, FCCP; Alan S. Go, MD; Shaun D. Goodman, MD, FACC; Ian A. Greer, MD, FRCP, FRCOG; Andreas Greinacher, MD; Jeremy Grimshaw, MD, PhD; Cindy Grines, MD; Jonathan L. Halperin, MD; Robert A. Harrington, MD; John Heffner, MD, MPH; John A. Heit, MD; Judith S. Hochman, MD, FACC; Dieter Horstkotte, MD, FESC; Russell D. Hull, MBBS, MSc, FCCP; Elaine Hylek, MD; Thomas M. Hyers, MD, FCCP; Mark R. Jackson, MD; Alan Jacobson, MD; Roman Jaeschke, MD, MSc; Ajay Kakkar BSc, PhD; Clive Kearon, MD, PhD, FCCP; Matthew Kraay; Michael R. Lassen, MD; Mark N. Levine, MD, MSc; Alessandro Liberati, MD; Gregory YH Lip, MD, FESC, FACC; Warren J. Manning, MD; M. Patricia Massicotte, MD, MSc, FRCPC, MSc; Thomas W. Meade, MD; Venu Menon, MD, FACC; Alan D. Michelson, MD; Nancy Miller, RN; Paul Monagle, MBBS, MSc, MD, FRACP, FRCPA, FCCP; Heather Munger, MLS; Christopher M. O’Connor, MD; Martin O’Donnell, MD; E. Magnus Ohman, MD, FCCP; Carlo Patrono, MD; Stephen G. Pauker, MD; Graham F. Pineo, MD; Leon Poller, MD; Jeffrey J. Popma, MD; Martin H. Prins, MD; Robert Raschke, MD, MS; Gary Raskob, PhD; Joel G. Ray, MD, MSc; Gerald Roth, MD; Ralph L. Sacco, MD; Deeb N. Salem, MD, FCCP; Meyer M. Samama, MD; Andrew Schafer; Sam Schulman, MD, PhD; Daniel Singer, MD; Michael Sobel, MD; Paul D. Stein, MD, FCCP; Marco Tangelder, MD; Victor F. Tapson, MD, FCCP; Philip Teal, MD; Raymond Verhaeghe, MD; David A. Vorchheimer, MD; Theodore E. Warkentin, MD; Jeffrey Weitz, MD; Robert G. Wilcox, MD

Dr. Bates has no conflicts of interest to disclose.

Dr. Greer has received honoraria for his participation on advisory boards and/or as a speaker at educational events from Aventis.

Dr. Hirsh has received research funding from AstraZeneca and has received honararia for his participation on advisory boards and/or as a speaker at educational events from AstraZeneca, Aventis Pharma, Sanofi-Synthelabo-Organon, Bristol-Myers Squibb, GlaxoSmithKline and Asahi.

This is the current release of the guideline.

This guideline updates a previous version: Ginsberg JS, Greer I, Hirsh J. Use of antithrombotic agents during pregnancy. Chest 2001 Jan;119(1 Suppl):122S-131S.

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