Approach Considerations

The decision to provide thromboprophylaxis to pregnant patients depends on the following:

Any prior personal history of VTE
The presence of high- versus low-risk thrombophilia
The setting in which a prior VTE occurred (pregnancy/estrogen-related, idiopathic, or in the setting of nonrecurrent risk factors such as fractures, surgery, or immobilization)

These factors affect the decision to provide prophylaxis, as well as the timing (antenatal or postpartum only) and intensity of therapy. Early recognition of risk factors and wide implementation of thromboprophylaxis guidelines in the UK found a significant decrease in their maternal mortality due to thromboembolisms.^[57]

The following recommendations are based on the table from ACOG Practice Bulletin 123, Published September 2011 (reaffirmed in 2014):^[58]

Table 2. Management of Pregnancy in a Patient With a History of VTE (Open Table in a new window)

Clinical Scenario	Antepartum Management	Postpartum Management
Low-risk thrombophilia without prior VTE	Surveillance without anticoagulation or prophylactic LMWH or UFH	Surveillance without anticoagulation OR postpartum anticoagulation in the presence of additional risk factors (eg, obesity, prolonged immobility, first-degree relative with VTE before age 50 years)
Low-risk thrombophilia with a single episode of VTE in a patient not receiving long-term anticoagulation therapy	Prophylactic or intermediate LMWH/UFH or surveillance without anticoagulation therapy	Anticoagulation therapy or intermediate-dose LMWH/UFH
High-risk thrombophilia (antithrombin deficiency, homozygous factor V Leiden, homozygous prothrombin mutation G20210A, double heterozygous factor V Leiden and prothrombin mutation G20210A) without prior VTE	Prophylactic LMWH or UFH	Anticoagulation therapy
High-risk thrombophilia with previous single episode of VTE in a patient not receiving long-term anticoagulation therapy	Prophylactic-, intermediate-dose, or adjusted-dose LMWH or UFH	Anticoagulation therapy or intermediate- or adjusted-dose LMWH/UFH for 6 weeks
No thrombophilia with single prior episode of VTE with a transient risk factor no longer present and VTE not associated with pregnancy- or estrogen-related risk factor	Surveillance without anticoagulation	Anticoagulation therapy
No thrombophilia with single prior episode of VTE associated with transient risk factor associated with pregnancy or estrogen related	Prophylactic-dose LMWH/UFH	Anticoagulation therapy
No thrombophilia with single prior episode VTE without associated risk factor in a patient not receiving long-term anticoagulation therapy	Prophylactic-dose LMWH/UFH	Anticoagulation therapy
Thrombophilia or no thrombophilia with 2 or more VTE episodes in a patient not receiving long-term anticoagulation therapy	Prophylactic or therapeutic dose of either LMWH or UFH	Anticoagulation therapy or therapeutic dose LMWH/UFH for 6 weeks
Thrombophilia or no thrombophilia with 2 or more VTE episodes in a patient receiving long-term anticoagulation therapy	Therapeutic dose of either LMWH or UFH	Resumption of long-term anticoagulation therapy
Abbreviations: LMWH, low molecular weight heparin; UFH, unfractionated heparin

A systematic review by Croles et al reported that antepartum or postpartum thrombosis prophylaxis, or both should be considered for women with antithrombin, protein C, or protein S deficiency or with homozygous factor V Leiden. Thrombosis prophylaxis on the basis of thrombophilia and family history alone should generally not be prescribed for women with heterozygous factor V Leiden, heterozygous prothrombin G20210A mutation, or compound heterozygous factor V Leiden and prothrombin G20210A.^[59]

Consultations

Consider consultation with a maternal fetal medicine specialist and/or hematologist.

Long-Term Monitoring

Postpartum therapeutic and prophylactic management of VTE is as listed above.

Estrogen-containing contraception has been shown to increase the risk of VTE 35-99 times above baseline.^[60]Therefore, estrogen-based contraception is contraindicated in a patient with a history of VTE or thrombophilia. Nonetheless, screening all women prior to initiating estrogen-containing contraception is not recommended by the ACOG.^[61]Contraceptive methods, including progestin-containing contraceptives, may be considered in women with a prior VTE or known thrombophilia.^[19]

Medication

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Table 1. Pregnancy Complications Associated with Thrombophilia ^{[21, 18]}

Thrombophilia	First-Trimester Loss	Late Fetal Loss	Preeclampsia	Abruption	Fetal Growth Restriction
Factor V Leiden, homozygous	2.71 (1.32-5.58)*	1.98 (0.4-9.69)	1.87 (0.44-7.88)	8.43 (0.41-171.20)	4.64 (0.19-115.68)
Factor V Leiden, heterozygous	1.68 (1.09-2.58)*	2.06 (1.1-3.86)*	2.19 (1.46-3.27)*	4.70 (1.13-19.59)*	2.68 (0.59-12.13)
Prothrombin, heterozygous	2.49 (1.24-5.00)*	2.66 (1.28-5.53)*	2.54 (1.52-4.23)*	7.71 (3.01-19.76)*	2.92 (0.62-13.70)
MTHFR C677T, homozygous	1.40 (0.77-2.55)	1.31 (0.89-1.91)	1.37 (1.07-1.76)*	1.47 (0.40-5.35)	1.24 (0.84-1.82)
Antithrombin deficiency	0.88 (0.17-4.48)	7.63 (0.3-196.36)	3.89 (0.16-97.19)	1.08 (0.06-18.12)	N/A
Protein C deficiency	2.29 (0.20-26.43)	3.05 (0.24-38.51)	5.15 (0.26-102.22)	5.93 (0.23-151.58)	N/A
Protein S deficiency	3.55 (0.35-35.72)	20.09 (3.7-109.15)*	2.83 (0.76-10.57)	2.11 (0.47-9.34)	N/A
Anticardiolipin antibodies	3.40 (1.33-8.68)*	3.30 (1.62-6.70)*	2.73 (1.65-4.51)*	1.42 (0.42-4.77)	6.91 (2.70-17.68)*
Lupus anticoagulant	2.97 (1.03-8.56)*	2.38 (0.81-6.70)	1.45 (0.76-2.75)	N/A	N/A
Acquired APCR	4.04 (1.67-9.76)*	0.90 (0.21-3.86)	1.80 (0.70-4.61)	1.25 (0.36-4.37)	N/A
Hyperhomocystinemia	6.25 (1.37-28.42)	0.98 (0.17-5.55)	3.49 (1.21-10.11)*	2.40 (0.36-15.89)	N/A
*Statistically significant Abbreviation: MTHFR, methylene tetrahydrofolate reductase deficiency

Table 2. Management of Pregnancy in a Patient With a History of VTE

Clinical Scenario	Antepartum Management	Postpartum Management
Low-risk thrombophilia without prior VTE	Surveillance without anticoagulation or prophylactic LMWH or UFH	Surveillance without anticoagulation OR postpartum anticoagulation in the presence of additional risk factors (eg, obesity, prolonged immobility, first-degree relative with VTE before age 50 years)
Low-risk thrombophilia with a single episode of VTE in a patient not receiving long-term anticoagulation therapy	Prophylactic or intermediate LMWH/UFH or surveillance without anticoagulation therapy	Anticoagulation therapy or intermediate-dose LMWH/UFH
High-risk thrombophilia (antithrombin deficiency, homozygous factor V Leiden, homozygous prothrombin mutation G20210A, double heterozygous factor V Leiden and prothrombin mutation G20210A) without prior VTE	Prophylactic LMWH or UFH	Anticoagulation therapy
High-risk thrombophilia with previous single episode of VTE in a patient not receiving long-term anticoagulation therapy	Prophylactic-, intermediate-dose, or adjusted-dose LMWH or UFH	Anticoagulation therapy or intermediate- or adjusted-dose LMWH/UFH for 6 weeks
No thrombophilia with single prior episode of VTE with a transient risk factor no longer present and VTE not associated with pregnancy- or estrogen-related risk factor	Surveillance without anticoagulation	Anticoagulation therapy
No thrombophilia with single prior episode of VTE associated with transient risk factor associated with pregnancy or estrogen related	Prophylactic-dose LMWH/UFH	Anticoagulation therapy
No thrombophilia with single prior episode VTE without associated risk factor in a patient not receiving long-term anticoagulation therapy	Prophylactic-dose LMWH/UFH	Anticoagulation therapy
Thrombophilia or no thrombophilia with 2 or more VTE episodes in a patient not receiving long-term anticoagulation therapy	Prophylactic or therapeutic dose of either LMWH or UFH	Anticoagulation therapy or therapeutic dose LMWH/UFH for 6 weeks
Thrombophilia or no thrombophilia with 2 or more VTE episodes in a patient receiving long-term anticoagulation therapy	Therapeutic dose of either LMWH or UFH	Resumption of long-term anticoagulation therapy
Abbreviations: LMWH, low molecular weight heparin; UFH, unfractionated heparin

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