Guideline Title
Inherited thrombophilias in pregnancy.
Bibliographic Source(s)
American College of Obstetricians and Gynecologists (ACOG). Inherited thrombophilias in pregnancy. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2011 Sep. 11 p. (ACOG practice bulletin; no. 124). [66 references] |
Guideline Status
This is the current release of the guideline.
This guideline updates a previous version: American College of Obstetricians and Gynecologists (ACOG). Inherited thrombophilias in pregnancy. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2010 Jul. 11 p. (ACOG practice bulletin; no. 113).
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ICD9CM:
Coagulation defects complicating pregnancy, childbirth, or the puerperium, antepartum condition or complication (649.33); Congenital deficiency of other clotting factors (286.3); Embolism and thrombosis of unspecified site (453.9)
MSH:
Pregnancy Complications, Hematologic; Thromboembolism; Venous Thromboembolism
MTH:
Antithrombin III Deficiency; Genetic screening method; Thromboembolism
PDQ:
thromboembolism; thrombolytic therapy; warfarin
SNOMEDCT:
Thromboembolic disorder (13713005); Thromboembolic disorder (371039008); Thromboembolism of vein (429098002)
SPN:
HEPARIN; LEGGING, COMPRESSION, NON-INFLATABLE
UMD:
Reagents, Molecular Assay, Gene Anomaly, Mutation (24-263); Reagents, Molecular Assay, Gene Anomaly, Mutation, F5 (24-410); Stockings, Compression (13-789)
ICD9CM:
Coagulation defects complicating pregnancy, childbirth, or the puerperium, antepartum condition or complication (649.33); Congenital deficiency of other clotting factors (286.3); Embolism and thrombosis of unspecified site (453.9)
MSH:
Anticoagulants; Antithrombin III Deficiency; Blood Coagulation Disorders, Inherited; Fibrinolytic Agents; Genetic Testing; Heparin; Heparin, Low-Molecular-Weight; Intermittent Pneumatic Compression Devices; International Normalized Ratio; Medical History Taking; Mutation; Pregnancy Complications; Pregnancy Complications, Hematologic; Protein C Deficiency; Protein S Deficiency; Risk Assessment; Stockings, Compression; Thromboembolism; Thrombolytic Therapy; Thrombophilia; Venous Thromboembolism; Warfarin
MTH:
Anticoagulants; Antithrombin III Deficiency; Compression Stockings; Fibrinolytic Agents; Genetic screening method; Heparin; Heparin, Low-Molecular-Weight; International Normalized Ratio; Medical Surveillance; Mutation; Pregnancy Complications; Thromboembolism; Warfarin
PDQ:
heparin; thromboembolism; thrombolytic therapy; warfarin
SNOMEDCT:
Anticoagulant (372862008); Anticoagulant (81839001); Antithrombin III deficiency (36351005); f - Family history (277652007); Factor V Leiden mutation (307091009); Genetic mutation (55446002); Genetic test (405824009); Graduated compression elastic hosiery (348681001); Heparin (372877000); Heparin (84812008); Heparin (96382006); International normalized ratio (165581004); Low molecular weight heparin (373294004); Low molecular weight heparin (87233003); Pregnancy complications (198881004); Pregnancy complications (90821003); Protein C deficiency disease (76407009); Protein S deficiency disease (1563006); Prothrombin G20210A mutation (440989002); Risk assessment (225338004); Surveillance (225419007); Thromboembolic disorder (13713005); Thromboembolic disorder (371039008); Thromboembolism of vein (429098002); Thrombolytic (303960004); Thrombolytic (372742009); Thrombolytic therapy (426347000); Thrombophilia (234467004); Thrombophilia (76612001); Warfarin (372756006); Warfarin (48603004)
SPN:
HEPARIN; LEGGING, COMPRESSION, NON-INFLATABLE
UMD:
Reagents, Molecular Assay, Gene Anomaly, Mutation (24-263); Reagents, Molecular Assay, Gene Anomaly, Mutation, F5 (24-410); Stockings, Compression (13-789)
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Disease/Condition(s)
- Inherited thrombophilias
- Factor V Leiden mutation
- Prothrombin G20210A mutation
- Protein C deficiency
- Protein S deficiency
- Antithrombin deficiency
- Pregnancy
- Venous thromboembolism
Guideline Category
Evaluation
Management
Prevention
Risk Assessment
Screening
Treatment
Clinical Specialty
Family Practice
Hematology
Medical Genetics
Obstetrics and Gynecology
Pharmacology
Intended Users
Advanced Practice Nurses
Physician Assistants
Physicians
Guideline Objective(s)
- To review common thrombophilias and their association with maternal venous thromboembolism risk and adverse pregnancy outcomes
- To review indications for screening to detect these conditions
- To review management options in pregnancy
Target Population
Pregnant and breastfeeding women with inherited thrombophilias
Interventions and Practices Considered
Risk Assessment/Screening
- Patient and family history
- Individualized risk assessment
- Screening for inherited thrombophilias
- Factor V Leiden mutation
- Prothrombin G20210A mutation
- Protein C deficiency
- Protein S deficiency
- Antithrombin deficiency
Management/Treatment
- Low molecular weight heparin (LMWH)
- Unfractionated heparin
- Warfarin
- Vitamin K antagonists
- Surveillance
- Compression stockings/pneumatic compression boots
- International normalized ratio monitoring
Note: Screening for methylenetetrahydrofolate reductase (MTHFR) gene mutations was considered but not recommended.
Major Outcomes Considered
- Incidence of venous thromboembolism
- Adverse pregnancy outcomes
- Adverse effects of therapy
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Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence
The MEDLINE database, the Cochrane Library, and the American College of Obstetricians and Gynecologists' own internal resources and documents were used to conduct a literature search to locate relevant articles published between January 1985 and February 2009. The search was restricted to articles published in the English language. Priority was given to articles reporting results of original research, although review articles and commentaries also were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document.
Guidelines published by organizations or institutions such as the National Institutes of Health and the American College of Obstetricians and Gynecologists were reviewed, and additional studies were located by reviewing bibliographies of identified articles. When reliable research was not available, expert opinions from obstetrician–gynecologists were used.
Number of Source Documents
Methods Used to Assess the Quality and Strength of the Evidence
Weighting According to a Rating Scheme (Scheme Given)
Rating Scheme for the Strength of the Evidence
Studies were reviewed and evaluated for quality according to the method outlined by the U.S. Preventive Services Task Force:
I: Evidence obtained from at least one properly designed randomized controlled trial.
II-1: Evidence obtained from well-designed controlled trials without randomization.
II-2: Evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group.
II-3: Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments also could be regarded as this type of evidence.
III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
Methods Used to Analyze the Evidence
Review of Published Meta-Analyses
Systematic Review
Description of the Methods Used to Analyze the Evidence
Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations
Analysis of available evidence was given priority in formulating recommendations. When reliable research was not available, expert opinions from obstetrician-gynecologists were used. See also the "Rating Scheme for the Strength of Recommendations" field regarding Level C recommendations.
Rating Scheme for the Strength of the Recommendations
Based on the highest level of evidence found in the data, recommendations are provided and graded according to the following categories:
Level A—Recommendations are based on good and consistent scientific evidence.
Level B—Recommendations are based on limited or inconsistent scientific evidence.
Level C—Recommendations are based primarily on consensus and expert opinion.
Cost Analysis
A formal cost analysis was not performed and published cost analyses were not reviewed.
Method of Guideline Validation
Internal Peer Review
Description of Method of Guideline Validation
Practice Bulletins are validated by two internal clinical review panels composed of practicing obstetrician-gynecologists generalists and sub-specialists. The final guidelines are also reviewed and approved by the American College of Obstetricians and Gynecologists (ACOG) Executive Board.
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Major Recommendations
The grades of evidence (I-III) and levels of recommendations (A-C) are defined at the end of "Major Recommendations" field.
The following recommendations are based on limited or inconsistent scientific evidence (Level B):
- Postpartum warfarin, low-molecular-weight heparin (LMWH), and unfractionated heparin anticoagulation may be used in women who breastfeed.
- Inherited thrombophilia testing in women who have experienced recurrent fetal loss or placental abruption is not recommended because it is unclear whether anticoagulation reduces recurrence.
- There is insufficient evidence to recommend screening or treatment for thrombophilias in women with previous intrauterine growth restriction (IUGR) or preeclampsia.
- Because of the lack of association between the methylenetetrahydrofolate reductase (MTHFR) mutation and negative pregnancy outcomes, screening with fasting homocysteine levels or MTHFR mutation analyses is not recommended.
The following recommendations are based primarily on consensus and expert opinion (Level C):
- Screening for inherited thrombophilias should include factor V Leiden mutation; prothrombin G20210A mutation; and antithrombin, protein C, and protein S deficiencies.
- Treatment recommendations for women with inherited thrombophilias are listed in the table below.
- All patients with inherited thrombophilias should undergo individualized risk assessment, which may modify management decisions.
Table. Recommended Thromboprophylaxis for Pregnancies Complicated by Inherited Thrombophilias*
Clinical Scenario |
Antepartum Management |
Postpartum Management |
Low-risk thrombophilia† without previous VTE |
Surveillance without anticoagulation or prophylactic LMWH or UFH |
Surveillance without anticoagulation therapy or postpartum anticoagulation therapy if the patient has additional risks factors‡ |
Low-risk thrombophilia† with a single previous episode of VTE—Not receiving long-term anticoagulation |
Prophylactic or intermediate-dose LMWH/UFH or surveillance without anticoagulation therapy |
Postpartum anticoagulation therapy or intermediate-dose LMWH/UFH |
High-risk thrombophilia§ without previous VTE |
Prophylactic LMWH or UFH |
Postpartum anticoagulation therapy |
High-risk thrombophilia§ with a single previous episode of VTE—Not receiving long-term anticoagulation |
Prophylactic, intermediate-dose, or adjusted-dose LMWH/UFH regimen |
Postpartum anticoagulation therapy or intermediate or adjusted-dose LMWH/UFH for 6 weeks (therapy level should be at least as high as antepartum treatment) |
No thrombophilia with previous single episode of VTE associated with transient risk factor that is no longer present—Excludes pregnancy- or estrogen-related risk factor |
Surveillance without anticoagulation therapy |
Postpartum anticoagulation therapy|| |
No thrombophilia with previous single episode of VTE associated with transient risk factor that was pregnancy or estrogen related |
Prophylactic-dose LMWH or UFH|| |
Postpartum anticoagulation therapy |
No thrombophilia with previous single episode of VTE without an associated risk factor (idiopathic)—Not receiving long-term anticoagulation therapy |
Prophylactic LMWH or UFH|| |
Postpartum anticoagulation therapy |
Thrombophilia or no thrombophilia with two or more episodes of VTE–Not receiving long-term anticoagulation therapy |
Prophylactic or therapeutic-dose LMWH
or
Prophylactic or therapeutic-dose UFH |
Postpartum anticoagulation therapy
or
Therapeutic-dose LMWH/UFH for 6 weeks |
Thrombophilia or no thrombophilia with two or more episodes of VTE–Receiving long-term anticoagulation therapy |
Therapeutic-dose LMWH/UFH |
Resumption of long-term anticoagulation therapy |
Abbreviations: LMWH, low molecular weight heparin; UFH, unfractionated heparin; VTE, venous thromboembolism.
*Postpartum treatment levels should be greater or equal to antepartum treatment. Treatment of acute VTE and management of antiphospholipid syndrome are addressed in other Practice Bulletins.
†Low-risk thrombophilia: factor V Leiden heterozygous; prothrombin G20210A heterozygous; protein C or protein S deficiency.
‡First-degree relative with a history of a thrombotic episode before age 50 years, or other major thrombotic risk factors (e.g., obesity, prolonged immobility).
§High-risk thrombophilia: antithrombin deficiency; double heterozygous for prothrombin G20210A mutation and factor V Leiden; factor V Leiden homozygous or prothrombin G20210A mutation homozygous.
||Surveillance without anticoagulation is supported as an alternative approach by some experts.
Definitions:
Grades of Evidence
I: Evidence obtained from at least one properly designed randomized controlled trial.
II-1: Evidence obtained from well-designed controlled trials without randomization.
II-2: Evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group.
II-3: Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments also could be regarded as this type of evidence.
III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
Levels of Recommendations
Level A—Recommendations are based on good and consistent scientific evidence.
Level B—Recommendations are based on limited or inconsistent scientific evidence.
Level C—Recommendations are based primarily on consensus and expert opinion.
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Evidence Supporting the Recommendations
Type of Evidence Supporting the Recommendations
The type of supporting evidence is identified and graded for each recommendation (see the "Major Recommendations" field).
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Benefits/Harms of Implementing the Guideline Recommendations
Potential Benefits
- Appropriate management of inherited thrombophilias in pregnancy
- Decrease in maternal venous thromboembolism risk
- Reduction of adverse pregnancy outcomes such as fetal loss, preeclampsia, fetal growth restriction, and placental abruption
Potential Harms
Bleeding risks associated with anticoagulation therapy
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Qualifying Statements
The information in these guidelines is designed to aid practitioners in making decisions about appropriate obstetric and gynecologic care. These guidelines should not be construed as dictating an exclusive course of treatment or procedure. Variations in practice may be warranted based on the needs of the individual patient, resources, and limitations unique to the institution or type of practice.
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Implementation of the Guideline
Description of Implementation Strategy
An implementation strategy was not provided.
Implementation Tools
Audit Criteria/IndicatorsFor information about availability, see the Availability of Companion Documents and Patient Resources fields below.
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Institute of Medicine (IOM) National Healthcare Quality Report Categories
IOM Care Need
Living with Illness
Staying Healthy
IOM Domain
Effectiveness
Patient-centeredness
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Identifying Information and Availability
Bibliographic Source(s)
American College of Obstetricians and Gynecologists (ACOG). Inherited thrombophilias in pregnancy. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2011 Sep. 11 p. (ACOG practice bulletin; no. 124). [66 references] |
Adaptation
Not applicable: The guideline was not adapted from another source.
Date Released
2010 Apr (revised 2011 Sep)
Guideline Developer(s)
American College of Obstetricians and Gynecologists - Medical Specialty Society
Source(s) of Funding
American College of Obstetricians and Gynecologists (ACOG)
Guideline Committee
American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Obstetrics
Composition of Group That Authored the Guideline
This Practice Bulletin was developed by the Committee on Practice Bulletins—Obstetrics with the assistance of Charles Lockwood, MD, and George Wendel, MD.
American College of Obstetricians and Gynecologists (ACOG) committees are created or abolished and their overall function defined by the Executive Board. Appointments are made for one year, with the understanding that such appointment may be continued for a total of three years. The majority of committee members are Fellows, but Junior Fellows also are eligible for appointment. Some committees may have representatives from other organizations when this is particularly appropriate to committee activities. The president elect appoints committee members annually.
Financial Disclosures/Conflicts of Interest
Guideline Status
This is the current release of the guideline.
This guideline updates a previous version: American College of Obstetricians and Gynecologists (ACOG). Inherited thrombophilias in pregnancy. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2010 Jul. 11 p. (ACOG practice bulletin; no. 113).
Guideline Availability
Electronic copies: None available
Print copies: Available for purchase from the American College of Obstetricians and Gynecologists (ACOG) Distribution Center, PO Box 933104, Atlanta, GA 31193-3104; telephone, 800-762-2264; e-mail: sales@acog.org. The ACOG Bookstore is available online at the ACOG Web site .
Availability of Companion Documents
A proposed performance measure is included in the original guideline document.
NGC Status
This NGC summary was completed by ECRI Institute on September 16, 2010. This NGC summary was updated by ECRI Institute on October 21, 2011.
Copyright Statement
This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.
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