Table 3.
Guideline summary: prevention of first VTE in pregnant women with hereditary thrombophilia
| American Society of Hematology (ASH) | Society of Obstetricians and Gynecologists of Canada (SOGC)*,235 | Royal College of Obstetricians and Gynecologists (RCOG)†,240 | American College of Obstetricians and Gynecologists (ACOG)‡,239 | American College of Chest Physicians (ACCP)§,237 |
|---|---|---|---|---|
| Heterozygosity for factor V Leiden or prothrombin gene mutation | ||||
| Antepartum: Regardless of family history of VTE, the ASH guideline panel suggests against using antepartum antithrombotic prophylaxis to prevent a first VTE (conditional recommendation, very low certainty in evidence about effects). | Antepartum: Clinical surveillance (no grade). | Antepartum: Clinical surveillance unless additional risk factors are present; with a weighted score of at least 3,|| thrombosis prophylaxis throughout the antepartum period should be considered; if the weighted score is only 2,|| prophylaxis should be considered from 28 weeks (D). | Antepartum: Either clinical surveillance or prophylactic LMWH or UFH (no grade). | Antepartum: For pregnant women who are heterozygous for factor V Leiden mutation or prothrombin gene mutation, suggest antepartum clinical surveillance (regardless of family history of VTE) (grade 2C). |
| Postpartum: For women without a family history of VTE, the ASH guideline panel suggests against antithrombotic prophylaxis in the postpartum period to prevent a VTE (conditional recommendation, very low certainty in evidence about effects). For women with a family history of VTE, the ASH guideline panel suggests against postpartum antithrombotic prophylaxis to prevent a first VTE (conditional recommendation, very low certainty in evidence about effects). | Postpartum: Clinical surveillance or prophylaxis if present in combination with any 2 of the following risk factors (each with an absolute risk of VTE <1% in isolation): BMI ≥30 kg/m2 at first antepartum visit (II-2B), smoking >10 cigarettes per day antepartum (II-2B), preeclampsia (II-2B), intrauterine growth restriction (II-2B), placenta previa (II-2B), emergency cesarean section (II-2B), peripartum or postpartum blood loss of >1 L or need for blood product replacement (II-2B), preterm delivery (III-B), stillbirth (III-B), or maternal disease (cardiac disease, systemic lupus erythematosus, sickle cell disease, inflammatory disease, varicose veins, gestational diabetes) (III-B). If prescribed, prophylaxis should be given for 6 weeks (II-3B). | Postpartum: Consider thrombosis prophylaxis for at least 10 days after delivery if additional risk factors are present with a weighted score of at least 1||; if there is a family history of VTE in a first-degree relative, thrombosis prophylaxis should be extended to 6 weeks (D). | Postpartum: Either clinical surveillance or anticoagulation if there are additional risk factors (first-degree relative with thrombotic episode before age 50 years or other major thrombotic risk factor (eg, obesity, prolonged immobility) (no grade). | Postpartum: For pregnant women who are heterozygous for factor V Leiden or prothrombin gene mutation, suggest postpartum clinical surveillance if there is no family history of VTE and postpartum prophylaxis with prophylactic- or intermediate-dose LMWH, or vitamin K antagonists targeted at an INR of 2.0 to 3.0 for 6 weeks if there is a family history of VTE rather than routine care (grade 2C). |
| Protein C deficiency | ||||
| Antepartum: Regardless of family history of VTE, the ASH guideline panel suggests against using antepartum antithrombotic prophylaxis to prevent a first VTE (conditional recommendation, very low certainty in evidence about effects). | Antepartum: Clinical surveillance (no grade). | Antepartum: Advice of a local expert should be sought and antepartum LMWH should be considered (D). | Antepartum: Either clinical surveillance or prophylactic LMWH or UFH (no grade). | Antepartum: For pregnant women who are protein C deficient, suggest antepartum clinical surveillance (regardless of family history of VTE) (grade 2C). |
| Postpartum: For women without a family history of VTE, the ASH guideline panel suggests against antithrombotic prophylaxis in the postpartum period to prevent a first VTE (conditional recommendation, very low certainty in evidence about effects). For women with a family history of VTE, the ASH guideline panel suggests postpartum antithrombotic prophylaxis to prevent a first VTE (conditional recommendation, very low certainty in evidence about effects) | Postpartum: Clinical surveillance or prophylaxis if in combination with any 2 of the following risk factors (each with an absolute risk of VTE <1% in isolation): BMI ≥30 kg/m2 at first antepartum visit (II-2B), smoking >10 cigarettes per day antepartum (II-2B), preeclampsia (II-2B), intrauterine growth restriction (II-2B), placenta previa (II-2B), emergency cesarean section (II-2B), peripartum or postpartum blood loss of >1 L or need for blood product replacement (II-2B), preterm delivery (III-B), stillbirth (III-B), or maternal disease (cardiac disease, systemic lupus erythematosus, sickle cell disease, inflammatory disease, varicose veins, gestational diabetes) (III-B). If prescribed, prophylaxis should be given for 6 weeks postpartum (II-3B). | Postpartum: Recommend LMWH for 6 weeks postpartum (D). | Postpartum: Either clinical surveillance or anticoagulation if there are additional risk factors (first-degree relative with thrombotic episode before age 50 years or other major thrombotic risk factor [eg, obesity, prolonged immobility]) (no grade). | Postpartum: For pregnant women who are protein C deficient, suggest postpartum clinical surveillance if there is no family history and postpartum prophylaxis with prophylactic- or intermediate-dose LMWH for 6 weeks if there is a family history of VTE rather than routine care (grade 2C). |
| Protein S deficiency | ||||
| Antepartum: Regardless of family history of VTE, the ASH guideline panel suggests against using antepartum antithrombotic prophylaxis to prevent a first VTE (conditional recommendation, very low certainty in evidence about effects). | Antepartum: Clinical surveillance (no grade). | Antepartum: Advice of a local expert should be sought and antepartum LMWH should be considered (D). | Antepartum: Either clinical surveillance or prophylactic LMWH or UFH (no grade). | Antepartum: For pregnant women who are protein S deficient, suggest antepartum clinical surveillance (regardless of family history of VTE) (grade 2C). |
| Postpartum: For women without a family history of VTE, the ASH guideline panel suggests against antithrombotic prophylaxis in the postpartum period to prevent a first VTE (conditional recommendation, very low certainty in evidence about effects). For women with a family history of VTE, the ASH guideline panel suggests postpartum antithrombotic prophylaxis to prevent a first VTE (conditional recommendation, very low certainty in evidence about effects). | Postpartum: Clinical surveillance or prophylaxis if in combination with any 2 of the following risk factors (each with an absolute risk of VTE <1% in isolation): BMI ≥30 kg/m2 at first antepartum visit (II-2B), smoking >10 cigarettes per day antepartum (II-2B), preeclampsia (II-2B), intrauterine growth restriction (II-2B), placenta previa (II-2B), emergency cesarean section (II-2B), peripartum or postpartum blood loss of >1 L or need for blood product replacement (II-2B), preterm delivery (III-B), stillbirth (III-B), or maternal disease (cardiac disease, systemic lupus erythematosus, sickle cell disease, inflammatory disease, varicose veins, gestational diabetes) (III-B). If prescribed, prophylaxis should be given for 6 weeks postpartum (II-3B). | Postpartum: Recommend LMWH for 6 weeks postpartum (D). | Postpartum: Either clinical surveillance or anticoagulation if there are additional risk factors (first-degree relative with thrombotic episode before age 50 years or other major thrombotic risk factor [eg, obesity, prolonged immobility]) (no grade). | Postpartum: For pregnant women who are protein S deficient, suggest postpartum clinical surveillance if there is no family history and postpartum prophylaxis with prophylactic- or intermediate-dose LMWH for 6 weeks rather than routine care if there is a family history of VTE (grade 2C). |
| Compound heterozygosity | ||||
| Antepartum: Regardless of family history, the ASH guideline panel suggests antepartum antithrombotic prophylaxis to prevent a first VTE (conditional recommendation, very low certainty in evidence about effects). | Antepartum: Prophylactic LMWH (IIIB). | Antepartum: Advice of a local expert should be sought and antepartum LMWH should be considered (D). | Antepartum: Prophylactic LMWH or UFH (no grade). | Antepartum: For pregnant women who are compound heterozygotes, suggest antepartum clinical surveillance (regardless of family history of VTE) (grade 2C). |
| Postpartum: Regardless of family history of VTE, the ASH guideline panel suggests postpartum antithrombotic prophylaxis to prevent a first VTE (conditional recommendation, very low certainty in evidence about effects). | Postpartum: Prophylactic LMWH (II-2B). Prophylaxis should be given for 6 weeks postpartum (II-3B). | Postpartum: Recommend LMWH for 6 weeks postpartum (D). | Postpartum: Anticoagulation (no grade). | Postpartum: For pregnant women who are compound heterozygotes, suggest postpartum clinical surveillance if there is no family history and postpartum prophylaxis with prophylactic- or intermediate-dose LMWH, or vitamin K antagonists targeted at an INR of 2.0 to 3.0 for 6 weeks rather than routine care of a family history of VTE (grade 2C). |
| Homozygosity for factor V Leiden or prothrombin gene mutation | ||||
| Antepartum: For women who are homozygous for the factor V Leiden mutation, regardless of family history, the ASH guideline panel suggests antepartum antithrombotic prophylaxis to prevent a first VTE (conditional recommendation, very low certainty in evidence about effects). For women homozygous for the prothrombin gene mutation who have no family history of VTE, the ASH guideline panel suggests against using antepartum antithrombotic prophylaxis to prevent a first VTE (conditional recommendation, very low certainty in evidence about effects). The ASH guideline panel was unable to make an evidence-based recommendation for women homozygous for the prothrombin gene mutation with a family history of VTE; however, panel members generally favored prophylaxis. | Antepartum: Prophylactic LMWH (II-2A for factor V Leiden; IIIB for prothrombin gene mutation). | Antepartum: Advice of a local expert should be sought, and antepartum LMWH should be considered (D). | Antepartum: Prophylactic LMWH or UFH (no grade). | Antepartum: For pregnant women who are homozygous for factor V Leiden or the prothrombin gene mutation and have no family history of VTE, suggest antepartum clinical vigilance (grade 2B). In the presence of a positive family history of VTE, suggest antepartum prophylactic- or intermediate-dose LMWH (grade 2B). |
| Postpartum: For women who are homozygous for the factor V Leiden mutation or for the prothrombin gene mutation, regardless of family history of VTE, the ASH guideline panel suggests postpartum antithrombotic prophylaxis to prevent a first VTE (conditional recommendation, very low certainty in evidence about effects) | Postpartum: Prophylactic LMWH (II-2B). Prophylaxis should be given for 6 weeks postpartum (II-3B). | Postpartum: Recommend LMWH for 6 weeks postpartum (D). | Postpartum: Anticoagulation (no grade). | Postpartum: For pregnant women who are homozygous for either factor V Leiden or the prothrombin gene mutation, suggest postpartum prophylaxis with prophylactic- or intermediate-dose LMWH, or vitamin K antagonists targeted at an INR of 2.0 to 3.0 for 6 weeks rather than routine care (regardless of family history) (grade 2B). |
| Antithrombin deficiency | ||||
| Antepartum: For women who have no family history of VTE, the ASH guideline panel suggests against using antepartum antithrombotic prophylaxis to prevent a first VTE (conditional recommendation, very low certainty in evidence about effects). For women who have a family history of VTE, the ASH guideline panel suggests antepartum antithrombotic prophylaxis to prevent a first venous thromboembolic event (conditional recommendation, very low certainty in evidence about effects). | Antepartum: Prophylactic LMWH (IIIB). | Antepartum: These women require specialist management by experts in hemostasis, and pregnancy antepartum prophylaxis should be provided from at least 28 weeks; if additional risk factors with a weighted score of at least 1|| are present, then prophylaxis should be provided from the first trimester (D). | Antepartum: Prophylactic LMWH or UFH (no grade). | Antepartum: For pregnant women who are antithrombin deficient, suggest antepartum clinical surveillance (regardless of family history of VTE) (grade 2C). |
| Postpartum: For women without a family history of VTE, the ASH guideline panel suggests against antithrombotic prophylaxis in the postpartum period to prevent a first venous thromboembolic event (conditional recommendation, very low certainty in evidence about effects) For women with a family history of VTE, the ASH guideline panel recommends postpartum antithrombotic prophylaxis to prevent a first venous thromboembolic event (strong recommendation, moderate certainty in evidence about effects). | Postpartum: Prophylactic LMWH (II-2B). Prophylaxis should be given for 6 weeks postpartum (II-3B). | Postpartum: Recommend LMWH for at least 6 weeks after delivery (D). | Postpartum: Anticoagulation (no grade). | Postpartum: For pregnant women who are antithrombin deficient, suggest postpartum clinical surveillance if there is no family history of VTE and postpartum prophylaxis with prophylactic-or intermediate-dose LMWH or vitamin K antagonists targeted at an INR of 2.0 to 3.0 for 6 weeks rather than routine care if there is a family history of VTE (grade 2C). |
BMI, body mass index; INR, international normalized ratio.
SOGC quality of evidence assessment.
I: Evidence obtained from at least 1 properly randomized controlled trial.
II-1: Evidence from well-designed controlled trials without randomization.
II-2: Evidence from well-designed cohort (prospective or retrospective) or case-control studies, preferably from more than 1 center or research group.
II-3: Evidence obtained from comparisons between times or places with or without the intervention.
III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
Recommendation grading.
A: There is good evidence to recommend the clinical preventative action.
B: There is fair evidence to recommend the clinical preventative action.
C: The existing evidence is conflicting and does not allow making a recommendation for or against use of the clinical preventative action; however, other factors may influence decision making.
D: There is fair evidence to recommend against the clinical preventative action.
E: There is good evidence to recommend against the clinical preventative action.
L: There is insufficient evidence (in quantity or quality) to make a recommendation; however, other factors may influence decision-making.
RCOG recommendation grading.
A: At least 1 meta-analysis, systematic review, or randomized controlled trial rated as 1++ (well conducted with a very low risk of bias) directly applicable to the target population, or a systematic review of randomized controlled trials or a body of evidence consisting principally of studies rated as 1+ (well-conducted meta-analysis, systematic reviews of randomized controlled trials, or randomized controlled trials with a low risk of bias) directly applicable to the target population and demonstrating overall consistency of results.
B: A body of evidence including studies rated as 2++ (high-quality systematic reviews of case-control or cohort studies or high-quality case control or cohort studies with a very low risk of confounding bias or chance and high probability that the relationship is causal) directly applicable to the target population and demonstrating overall consistency of results, or extrapolated evidence from studies rated as 1++ (well conducted with a very low risk of bias) or 1+ (well-conducted meta-analysis, systematic reviews of randomized controlled trials, or randomized controlled trials with a low risk of bias).
C: A body of evidence including studies rated as 2+ (well-conducted case-control or cohort studies with a low risk of confounding bias or chance and a moderate probability that the relationship is causal) directly applicable to the target population and demonstrating overall consistency of results, or extrapolated evidence from studies rated as 2++ (high-quality systematic reviews of case-control or cohort studies or high-quality case-control or cohort studies with a very low risk of confounding bias or chance and high probability that the relationship is causal).
D: Evidence is level 3 (nonanalytical studies [eg, case reports or case series]) or 4 (expert opinion), or extrapolated evidence from studies rated as 2+ (well-conducted case-control or cohort studies with a low risk of confounding bias or chance and a moderate probability that the relationship is causal).
ACOG recommendation grading.
Level A: based on good and consistent scientific evidence.
Level B: based on limited or inconsistent scientific evidence.
Level C: based primarily on consensus and expert opinion.
ACCP recommendation grading.
1A: Strong recommendation, high-quality evidence.
1B: Strong recommendation, moderate-quality evidence.
1C: Strong recommendation, low- or very-low-quality evidence.
2A: Weak recommendation, high-quality evidence.
2B: Weak recommendation, moderate-quality evidence.
2C: Weak recommendation, low- or very-low-quality evidence.
Risk factor weighting.
+1 (for each risk factor): immobility and/or dehydration; current systemic infection, preeclampsia in current pregnancy, assisted reproduction (antepartum only), multiple pregnancy, elective cesarean delivery, midcavity or rotational operative delivery, prolonged labor (>24 h), postpartum hemorrhage (>1 L or transfusion), preterm birth <37 weeks in current pregnancy, gross varicose veins, smoker, parity ≥3, obesity with BMI ≥30, age >35 years, family history of unprovoked or estrogen-related VTE in first-degree relative.
+2 (for each risk factor): cesarean delivery in labor, obesity with BMI ≥40.
+3 (for each risk factor): hyperemesis, any surgical procedure except immediate repair of the perineum, medical comorbidity (eg, cancer, heart failure, active systemic lupus erythematosus, inflammatory polyarthropathy or inflammatory bowel disease, nephrotic syndrome, type I diabetes mellitus with nephropathy, sickle cell disease, current intravenous drug use.
+4 (for each risk factor): ovarian hyperstimulation syndrome (first trimester only).