What is the recommended management for pregnant women with a history of coagulation disorders or at high risk of thromboembolic events?

Management of Pregnant Women with Coagulation Disorders or High Thromboembolic Risk

For pregnant women with a history of unprovoked or hormone-associated VTE, antepartum prophylactic anticoagulation with LMWH is strongly recommended, and all women with prior VTE should receive postpartum anticoagulation for at least 6 weeks. 1

Acute VTE Treatment in Pregnancy

• LMWH is the anticoagulant of choice over unfractionated heparin for treating acute VTE during pregnancy, with either once-daily or twice-daily dosing acceptable. 1, 2
• Continue therapeutic anticoagulation throughout pregnancy and for at least 6 weeks postpartum (minimum total duration of 6 months). 1, 2
• Routine monitoring of anti-FXa levels is not recommended for dose adjustment. 1
• For low-risk acute VTE, outpatient management is preferred over hospital admission. 1

Primary Prevention Based on VTE History

Women with Prior VTE

History of unprovoked or hormone-associated VTE:

• Strongly recommend antepartum prophylactic LMWH throughout pregnancy. 1
• Strongly recommend postpartum anticoagulation for at least 6 weeks. 1
• The recurrence risk is 3.6% for unprovoked VTE and 6.4% for hormone-associated VTE without prophylaxis. 1

History of VTE provoked by transient non-hormonal risk factor (surgery, trauma, immobilization):

• Antepartum clinical surveillance is suggested (no prophylaxis needed). 1
• Postpartum anticoagulation is still strongly recommended for at least 6 weeks. 1
• The recurrence risk is only 1.1% antepartum in this group. 1

Multiple prior VTE episodes:

• Use antepartum prophylactic, intermediate-dose, or adjusted-dose LMWH throughout pregnancy. 2
• Continue postpartum anticoagulation. 2

Primary Prevention Based on Thrombophilia Type

High-Risk Thrombophilias

Antithrombin deficiency:

• Strongly recommend postpartum prophylaxis for women with family history of VTE. 1
• Suggest antepartum prophylaxis if family history of VTE is present. 1
• Without family history: antepartum surveillance acceptable, but postpartum prophylaxis should be considered. 1

Homozygous Factor V Leiden:

• Suggest antepartum prophylaxis regardless of family history. 1
• Suggest postpartum prophylaxis for 6 weeks regardless of family history. 1

Homozygous prothrombin gene mutation:

• Without family history: suggest against antepartum prophylaxis, but panel members generally favor it. 1
• Suggest postpartum prophylaxis for 6 weeks regardless of family history. 1

Compound heterozygotes (Factor V Leiden + prothrombin mutation):

• Suggest postpartum prophylaxis for 6 weeks regardless of family history. 1
• With family history of VTE: suggest antepartum prophylaxis. 1

Lower-Risk Thrombophilias

Heterozygous Factor V Leiden or prothrombin gene mutation:

• Antepartum clinical surveillance is recommended regardless of family history. 1, 3
• Without family history of VTE: suggest against postpartum prophylaxis. 1
• With family history of VTE: recommend postpartum prophylactic LMWH for 6 weeks. 1, 3

Protein C or Protein S deficiency:

• Antepartum clinical surveillance regardless of family history. 1
• Without family history: clinical surveillance postpartum. 1
• With family history: consider postpartum prophylaxis. 1

Additional Risk Factor Assessment for Postpartum Prophylaxis

Consider postpartum prophylaxis (at least 10 days, extend to 6 weeks with family history of VTE) if ≥2 of the following are present: 1

• BMI ≥30 kg/m² at first visit 1
• Smoking >10 cigarettes/day 1
• Preeclampsia 1
• Intrauterine growth restriction 1
• Placenta previa 1, 4
• Emergency cesarean section 1, 4
• Blood loss >1L or transfusion requirement 1, 4
• Preterm delivery 1, 4
• Stillbirth 1
• Maternal comorbidities (cardiac disease, SLE, sickle cell disease, inflammatory disease) 1

Anticoagulant Selection and Safety

Preferred agents during pregnancy:

• LMWH (enoxaparin, dalteparin) is preferred over UFH due to ease of use, lower adverse event rates, and no need for monitoring. 1, 5, 6
• UFH is an acceptable alternative. 1

Contraindicated agents:

• Warfarin and other vitamin K antagonists should be avoided during pregnancy (except possibly in mechanical heart valves after thorough risk-benefit discussion) due to embryopathy risk and fetal bleeding. 2, 6
• Aspirin use in the last 3 months of pregnancy requires physician direction due to potential complications. 7

Safe during breastfeeding:

• UFH, LMWH, warfarin, acenocoumarol, fondaparinux, and danaparoid are all safe options. 1

Peripartum Anticoagulation Management

• For women on therapeutic-dose LMWH: suggest scheduled delivery with prior discontinuation of anticoagulation. 1
• For women on prophylactic-dose LMWH: suggest against scheduled delivery with discontinuation. 1

Special Situations

Assisted reproductive technology:

• Suggest against prophylaxis in unselected women. 1
• Suggest prophylaxis for women who develop severe ovarian hyperstimulation syndrome. 1

Superficial vein thrombosis:

• Suggest LMWH over no anticoagulation for proven acute superficial vein thrombosis. 1

Common Pitfalls to Avoid

• Do not withhold antepartum prophylaxis in women with unprovoked or hormone-associated prior VTE—the recurrence risk is substantial (3.6-6.4%). 1
• Do not forget postpartum prophylaxis even in women who did not receive antepartum prophylaxis—the postpartum period carries the highest VTE risk. 1
• Do not assume heterozygous Factor V Leiden or prothrombin mutation alone requires antepartum prophylaxis without family history—surveillance is adequate. 1, 3
• Do not use warfarin during pregnancy except in exceptional circumstances after thorough counseling. 2, 6
• Do not overlook additional postpartum risk factors (obesity, cesarean section, hemorrhage) that may warrant prophylaxis even without thrombophilia. 1, 4