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Deep vein thrombosis and pulmonary embolism in pregnancy: Prevention

Authors: David R Schwartz, MD, Atul Malhotra, MD, Steven E Weinberger, MD

Section Editors: Lawrence LK Leung, MD, Charles J Lockwood, MD, MHCM, Jess Mandel, MD
Deputy Editor: Geraldine Finlay, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Aug 2017. | This topic last updated: Apr 14, 2016.

INTRODUCTION — Pregnancy and the puerperium are well-established risk factors for deep vein
thrombosis (DVT) and pulmonary embolism (PE), which are collectively referred to as venous
thromboembolic disease (VTE). The need for thromboprophylaxis should be assessed antepartum,
postpartum and at any time the patient transitions from the outpatient to the inpatient setting. When it is
determined that thromboprophylaxis is warranted, an appropriate strategy should be selected and prescribed.

Thromboprophylaxis can be pharmacologic (ie, anticoagulation) or mechanical (eg, intermittent pneumatic

compression devices or graduated compression stockings). Indications, method and duration of
thromboprophylaxis in pregnant women are the major focuses of this topic. Issues concerning the use of
anticoagulants during pregnancy and prevention of VTE in medical, surgical, and gynecologic patients are
discussed separately. (See "Use of anticoagulants during pregnancy and postpartum" and "Prevention of
venous thromboembolic disease in acutely ill hospitalized medical adults" and "Prevention of venous
thromboembolic disease in surgical patients".)

RATIONALE — Pregnancy and the puerperium are risk factors for the development of venous
thromboembolism (VTE). This risk is thought to be due to venous stasis of the lower extremities, endothelial
injury and the hypercoagulable state that occurs during pregnancy. The incidence VTE is increased
throughout all trimesters of pregnancy but is highest during the postpartum period. Factors that may further
augment the risk include a prior history of VTE, hospitalization for an acute illness or cesarean delivery, and
the presence of an inherited thrombophilia (eg, factor V Leiden mutation prothrombin gene mutation,
antithrombin III, protein C, or protein S deficiencies). (See "Deep vein thrombosis in pregnancy:
Epidemiology, pathogenesis, and diagnosis", section on 'Pathogenesis'.)

INDICATIONS — Although pregnancy and the puerperium are risk factors for the development of VTE, the
vast majority of pregnant women do not require thromboprophylaxis. However, thromboprophylaxis is
typically targeted at those who are considered to be at greatest risk for the development of VTE during the
antepartum and postpartum periods. The indications for thromboprophylaxis in this particular population of
patients are discussed in this section.

Outpatient thromboprophylaxis — The indications for thromboprophylaxis differ for antepartum and
postpartum women.

Antepartum — All antepartum women should be subjected to vigilant clinical surveillance throughout
pregnancy for the signs and symptoms of VTE. Pharmacologic thromboprophylaxis can be administered to a
select population of antepartum women considered at high risk for VTE. We agree with the 2012 American
College of Chest Physicians (ACCP) and 2013 American College of Obstetricians and Gynecologists
(ACOG) guidelines on the selection criteria for antepartum pharmacologic thromboprophylaxis during
pregnancy (table 1) [1,2]. In each case the decision to administer antepartum pharmacologic
thromboprophylaxis should carefully weigh the benefits of VTE prevention against the risks of bleeding and
fetal complications.

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Data are insufficient to support routine outpatient pharmacologic thromboprophylaxis for most pregnant
women. Pharmacologic prophylaxis may be considered in patients with a history of a single idiopathic,
pregnancy-associated or estrogen-associated VTE, and in those with a history of multiple VTEs, regardless
of the cause. Pharmacologic prophylaxis is also considered for patients with a known thrombophilia and in
those with persistent risk factors and a prior history of VTE. The use of pharmacologic prophylaxis in
pregnant patients with a known thrombophilia is discussed in more detail separately. (See "Inherited
thrombophilias in pregnancy" and "Screening for inherited thrombophilia in asymptomatic individuals".)

The evidence to support pharmacologic thromboprophylaxis in the indicated populations is indirect, and
largely based upon epidemiologic studies, small retrospective studies of thromboprophylaxis in high risk
populations, and clinical experience [1-8]. Nonetheless, studies consistently report the highest incidence of
VTE in those with high risk variants of inherited thrombophilia and persistent risk factors in those with a prior
history of VTE. (See "Inherited thrombophilias in pregnancy".)

Pregnant women who have had a prior VTE related to a high estrogen state (eg, prior pregnancy or estrogen-
related VTE) are considered candidates for thromboprophylaxis because these risk factors are likely to
increase the chances of recurrent VTE during pregnancy. In contrast, those women in whom a transient risk
factor for prior VTE (eg, trauma, immobility, surgery) is identified, the likelihood of recurrence is presumed to
be lower. Thus, clinical surveillance is preferred over pharmacologic thromboprophylaxis for those without
persistent risk factors, unless multiple VTEs have occurred. (See "Overview of the causes of venous
thrombosis".)

Women who are already receiving anticoagulant therapy should have the need for ongoing therapeutic
anticoagulation reassessed at the beginning of the pregnancy. If it is determined that therapeutic
anticoagulation is necessary, women who are receiving oral anticoagulation (direct thrombin and factor Xa
inhibitors and warfarin) should have their anticoagulant regimen converted to a heparin-based regimen. The
timing of this conversion is discussed in more detail separately. (See "Use of anticoagulants during
pregnancy and postpartum", section on 'Switching from oral anticoagulants to LMW heparin'.)

The choice of regimen and duration of prophylaxis are discussed separately. (See 'Administration' below.)

Postpartum — All postpartum women should be subjected to vigilant clinical surveillance for the signs
and symptoms of VTE. Pharmacologic thromboprophylaxis can be administered to a select population of
postpartum women considered at high risk for VTE. We agree with the 2012 ACCP and 2013 ACOG
guidelines on the selection criteria for pharmacologic thromboprophylaxis for postpartum women (table 1)
[1,2]. The decision to administer postpartum pharmacologic thromboprophylaxis should be individualized for
each patient with careful assessment of the benefits and harms.

Data are insufficient to support routine outpatient pharmacologic thromboprophylaxis for most women in the
postpartum period. Pharmacologic prophylaxis may be considered in patients with a history of prior VTE
(single or multiple) regardless of the provoking factor (transient or persistent, inherited thrombophilia) and in a
subset of patients with inherited thrombophilia without a personal or family history of VTE. The use of
pharmacologic prophylaxis in patients with a known thrombophilia is discussed in more detail separately.
(See "Inherited thrombophilias in pregnancy" and "Screening for inherited thrombophilia in asymptomatic
individuals".)

The rationale for the use of thromboprophylaxis in the postpartum period is similar to that provided for the
antepartum period [1-9]. However, the threshold for anticoagulation is lowered in the postpartum setting
largely because the risk of VTE is increased, and the potential for the more serious adverse effects of
anticoagulation, including placental hemorrhage, spinal hematoma and fetal hemorrhage, is no longer a
consideration. Compared with the antepartum period, VTE, especially pulmonary embolism, is two to five
times more common in the puerperium with some epidemiologic evidence suggesting persistent risk for six
weeks beyond delivery [9-14]. (See "Inherited thrombophilias in pregnancy", section on 'Prevention of VTE'

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and "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis", section on 'Timing
during pregnancy'.)

The choice of regimen and duration of prophylaxis are discussed separately. (See 'Administration' below.)

Inpatient thromboprophylaxis

Antepartum admission — There are insufficient data to support the routine use of thromboprophylaxis
for every woman hospitalized during pregnancy or postpartum. Women who are candidates for outpatient
pharmacologic thromboprophylaxis are also candidates for prophylaxis as an inpatient. Select women who do
not meet the criteria for outpatient thromboprophylaxis may benefit from thromboprophylaxis during an acute
hospitalization. A decision regarding the use of pharmacologic thromboprophylaxis in this setting must be
made on an individual basis with careful assessment of the risk of VTE and the potential harms of
anticoagulation. (See 'Outpatient thromboprophylaxis' above.)

Examples of women who may be considered at moderate to high risk for VTE during hospitalization include
those admitted for medical or surgical reasons (eg, pneumonia, sepsis, orthopedic injury), patients on
prolonged bedrest (>3 days) and those with additional or multiple accepted risk factors for VTE during
pregnancy (eg, obesity, older maternal age, critical illness, malignancy, ovarian hyperstimulation, multiparity)
[15].

The risk of bleeding with pharmacologic prophylaxis is increased in patients with serious or severe bleeding
unrelated to pregnancy, those at risk of severe bleeding because of imminent vaginal or cesarean delivery, or
at risk of serious or severe bleeding due to antepartum complications (eg, placental abruption, placenta
previa, expanding subchorionic hematoma).

The optimal method of thromboprophylaxis in hospitalized women is not known. Options include early
ambulation, mechanical methods and/or pharmacologic agents. The benefits of each form of
thromboprophylaxis should be carefully weighed against the risks and individualized to each hospitalized
patient.

Indirect support for the use of thromboprophylaxis in hospitalized pregnant women is provided by the known
increased risk of VTE during pregnancy together with the established risk of VTE during hospitalization for
nonpregnant patients [16]. The risk of VTE in pregnant women hospitalized for non-delivery reasons was
examined in an analysis of a national database of over 200,000 women aged 15 to 44 years who had one or
more pregnancies from 1997 to 2010 [17]. Admission to the hospital for non-delivery reasons was associated
with a risk of VTE that was 18-fold higher during hospitalization (absolute rate, 1752 per 100,00 person
years) and 6-fold higher for the 28 days after discharge (676 per 100,00 person years) when compared with
other times spent outside the hospital. The highest rates were observed in those pregnant with a body mass
index (BMI) >30 kg/m2, maternal age >35 years, an admission during the third trimester, and a hospital stay
>3 days. This study suggests that the risk of VTE in hospitalized pregnant women is similar to that of high risk
hospitalized patients in the general population in whom thromboprophylaxis is frequently prescribed. Further
study is needed to elucidate the efficacy and safety of mechanical or pharmacologic thromboprophylaxis in
antepartum hospitalized patients. (See "Prevention of venous thromboembolic disease in acutely ill
hospitalized medical adults".)

The duration of prophylaxis is discussed separately. (See 'Administration' below.)

Cesarean section — Cesarean section (CS) is associated with an increased risk of VTE, especially when
performed emergently. Despite an increase in relative risk, the absolute increase in VTE incidence is thought
to be low. Observational data suggest that the risk for clinically important events is similar to that seen in low
risk surgical patients for whom no routine thromboprophylaxis other than early ambulation is recommended
[18]. As such, we and others prefer early ambulation and/or mechanical devices (eg, intermittent pneumatic
compression) in those patients who undergo a CS who do not have any additional risk factors for VTE [1,2].
The addition of pharmacologic prophylaxis after CS is frequently considered for women with additional or

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multiple risk factors [1,2]. Guideline recommendations from the ACCP and the ACOG for VTE prevention in
the patient who undergoes a CS are discussed in detail separately. (See "Cesarean delivery: Preoperative
planning and patient preparation", section on 'Thromboembolism prophylaxis'.)

ADMINISTRATION

Pharmacologic prophylaxis — In contrast to anticoagulation of nonpregnant women, the choice of

anticoagulant during pregnancy needs to take into account fetal safety and maternal peripartum issues (eg,
unpredictable onset of labor, use of neuraxial anesthesia for management of labor pain). Heparins are used
for most pregnant women because they do not cross the placenta and do not anticoagulate the fetus. Low
molecular weight heparin (LMWH)-based regimens are generally preferred. Unfractionated heparin is
preferred over LMWH in patients with severe renal insufficiency (eg, creatinine clearance <30 mL/min),
because LMWH metabolism is exclusively renal, while metabolism of unfractionated heparin is renal and
hepatic.

Heparins can be administered during pregnancy at different doses depending upon the risk of
thromboembolism and desired degree of anticoagulation (table 2). In general, the following terms apply: (See
"Use of anticoagulants during pregnancy and postpartum".)

● Prophylactic dose anticoagulation refers to the use of low doses of anticoagulants (eg, enoxaparin 40 mg
subcutaneously once daily), which aims to reduce the risk of thromboembolism while minimizing
bleeding complications

● Intermediate dose anticoagulation refers to the adjustment of prophylactic dose anticoagulation with
weight gain during pregnancy (eg, enoxaparin 40 mg subcutaneously twice daily)

● Therapeutic dose anticoagulation refers to the use of anticoagulants at doses typically reserved for
treatment of thromboembolic disease (eg, enoxaparin 1 mg/kg subcutaneously twice daily). Despite the
nomenclature, therapeutic dosing may be used prophylactically (ie, to prevent thromboembolism).

When LMWH is administered for venous thromboembolism (VTE) prophylaxis in a patient without a
thrombophilia, prophylactic or intermediate doses are used. Therapeutic dosing is used when prophylactic or
intermediate dosing is thought to be insufficient for thromboembolism prophylaxis in some patients at very
high risk of thromboembolism. The administration of prophylactic, intermediate and therapeutic heparin
during pregnancy is discussed in more detail separately. (See "Use of anticoagulants during pregnancy and
postpartum", section on 'Dosing and laboratory monitoring'.)

Mechanical prophylaxis — The efficacy of mechanical thromboprophylaxis (eg, frequent left-lateral

decubitus positioning during late pregnancy, graduated elastic compression stockings, and pneumatic
compression devices) during pregnancy or the puerperium is unknown because there is a paucity of
evidence. In a study of 10 pregnant women, venous Doppler ultrasound demonstrated that graduated
compression stockings increased femoral vein flow velocity during late pregnancy [19]. Nonetheless, the use
of mechanical prophylaxis following cesarean section and for hospitalized women during pregnancy is
considered safe and is discussed above. (See 'Inpatient thromboprophylaxis' above.)

DURATION — Outpatient antepartum pharmacologic thromboprophylaxis should be continued through the

pregnancy [1,20]. Management of anticoagulation in the final weeks of pregnancy and discontinuation for
labor are discussed in more detail separately. (See "Use of anticoagulants during pregnancy and
postpartum".)

The optimal duration of outpatient postpartum thromboprophylaxis is unknown. On the basis of clinical
experience and estimated risk, we agree with the 2012 American College of Chest Physicians (ACCP)
Clinical Practice Guidelines that suggest at least six weeks, with consideration for a longer duration of up to
three months, particularly in those at greatest risk (eg, persistent risk factors for thrombosis) [1]. (See "Deep
vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis", section on 'Risk factors'.)

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When thromboprophylaxis is administered during hospitalization (eg, acute illness or cesarean section), it
should continue until the patient is ambulatory, provided there is no indication for outpatient
thromboprophylaxis. Extended prophylaxis (ie, after discharge) is considered by some physicians to be
beneficial in select circumstances (eg, patient with a cesarean section who is assessed to be at very high risk
or who has multiple persistent additional risk factors for venous thromboembolism [VTE]) [1]. (See "Cesarean
delivery: Preoperative planning and patient preparation", section on 'Thromboembolism prophylaxis'.)

The initiation, timing and transition of thromboprophylaxis during pregnancy, labor, and delivery as well as
during lactation are discussed separately. (See "Use of anticoagulants during pregnancy and postpartum".)

COMPLICATIONS — Heparin has several side effects, including bleeding, thrombocytopenia, with or without
associated thrombosis, and osteoporosis. These adverse effects can occur even at prophylactic doses and
are more likely with long-term use. Complications of anticoagulants are discussed elsewhere. (See "Deep
vein thrombosis and pulmonary embolism in pregnancy: Treatment" and "Use of anticoagulants during
pregnancy and postpartum".)

SUMMARY AND RECOMMENDATIONS

● The risk of venous thromboembolism (VTE) is increased in all trimesters of pregnancy, especially the
postpartum period. Although most women do not require thromboprophylaxis, those who are considered
to be at greatest risk are generally targeted for VTE prevention. (See 'Rationale' above.)

● For most non-hospitalized pregnant women, we suggest observation rather than pharmacologic
prophylaxis for VTE (Grade 2C). We suggest antepartum pharmacologic prophylaxis for patients with a
history of a single idiopathic, pregnancy-associated or estrogen-associated VTE, and in those with a
history of multiple VTEs, regardless of the cause (Grade 2C). Pharmacologic prophylaxis is also
considered for patients with a known thrombophilia and a history of VTE and for patients with certain
"high risk" thrombophilias plus a family history of VTE. (See 'Antepartum' above.)

● For most postpartum women, we suggest observation rather than pharmacologic prophylaxis for VTE
(Grade 2C). We suggest postpartum pharmacologic prophylaxis in patients with a history of prior VTE
(single or multiple) regardless of the provoking factor (transient or persistent, inherited thrombophilia)
and in a subset of patients with inherited thrombophilia without a personal history of VTE (Grade 2C).
(See 'Postpartum' above.)

● For most pregnant women who are hospitalized antenatally for non-delivery reasons, we use the same
criteria for pharmacologic thromboprophylaxis as we do in the outpatient setting. Select women who do
not meet the criteria for outpatient thromboprophylaxis may benefit from thromboprophylaxis during an
acute hospitalization. (See 'Antepartum admission' above.)

● For women who undergo a cesarean section and have no additional risk factors for VTE, we suggest
early ambulation or the use of mechanical devices rather than pharmacologic thromboprophylaxis
(Grade 2C). For women who undergo a cesarean section and have additional risk factors for VTE, we
suggest the use of both pharmacologic and mechanical thromboprophylaxis (Grade 2C). (See 'Cesarean
section' above.)

● For women in whom the decision is made to administer pharmacologic prophylaxis, heparin-based
regimens are safer than oral anticoagulants. We suggest low molecular weight heparin rather than
unfractionated heparin provided the patient does not have renal insufficiency (eg, creatinine clearance
<30 mL/min) (Grade 2C). Heparin regimens are typically administered during pregnancy at different
doses depending upon the risk of thromboembolism and desired degree of anticoagulation (prophylactic,
intermediate, therapeutic) (table 2). (See 'Administration' above.)

● Antepartum pharmacologic thromboprophylaxis should be continued until delivery. We suggest that

postpartum pharmacologic thromboprophylaxis be continued for six weeks to three months. Following

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cesarean section, thromboprophylaxis is continued until the patient is ambulatory. (See 'Duration' above.)

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REFERENCES

1. Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy:
Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e691S.
2. American College of Obstetricians and Gynecologists Women's Health Care Physicians. ACOG
Practice Bulletin No. 138: Inherited thrombophilias in pregnancy. Obstet Gynecol 2013; 122:706.
Reaffirmed 2017.
3. Haemostasis and Thrombosis Task Force, British Committee for Standards in Haematology.
Investigation and management of heritable thrombophilia. Br J Haematol 2001; 114:512.
4. Pabinger I, Grafenhofer H, Kaider A, et al. Risk of pregnancy-associated recurrent venous
thromboembolism in women with a history of venous thrombosis. J Thromb Haemost 2005; 3:949.
5. Roeters van Lennep JE, Meijer E, Klumper FJ, et al. Prophylaxis with low-dose low-molecular-weight
heparin during pregnancy and postpartum: is it effective? J Thromb Haemost 2011; 9:473.
6. Dargaud Y, Rugeri L, Vergnes MC, et al. A risk score for the management of pregnant women with
increased risk of venous thromboembolism: a multicentre prospective study. Br J Haematol 2009;
145:825.
7. Pettilä V, Kaaja R, Leinonen P, et al. Thromboprophylaxis with low molecular weight heparin (dalteparin)
in pregnancy. Thromb Res 1999; 96:275.
8. Bain E, Wilson A, Tooher R, et al. Prophylaxis for venous thromboembolic disease in pregnancy and the
early postnatal period. Cochrane Database Syst Rev 2014; :CD001689.
9. Kamel H, Navi BB, Sriram N, et al. Risk of a thrombotic event after the 6-week postpartum period. N
Engl J Med 2014; 370:1307.
10. Marik PE, Plante LA. Venous thromboembolic disease and pregnancy. N Engl J Med 2008; 359:2025.
11. Heit JA, Kobbervig CE, James AH, et al. Trends in the incidence of venous thromboembolism during
pregnancy or postpartum: a 30-year population-based study. Ann Intern Med 2005; 143:697.
12. Simpson EL, Lawrenson RA, Nightingale AL, Farmer RD. Venous thromboembolism in pregnancy and
the puerperium: incidence and additional risk factors from a London perinatal database. BJOG 2001;
108:56.
13. Sultan AA, West J, Tata LJ, et al. Risk of first venous thromboembolism in and around pregnancy: a
population-based cohort study. Br J Haematol 2012; 156:366.
14. Stein PD, Hull RD, Kayali F, et al. Venous thromboembolism in pregnancy: 21-year trends. Am J Med
2004; 117:121.
15. http://www.nice.org.uk/nicemedia/live/12695/47195/47195.pdf (Accessed on November 15, 2013).
16. Heit JA, Melton LJ 3rd, Lohse CM, et al. Incidence of venous thromboembolism in hospitalized patients
vs community residents. Mayo Clin Proc 2001; 76:1102.
17. Abdul Sultan A, West J, Tata LJ, et al. Risk of first venous thromboembolism in pregnant women in
hospital: population based cohort study from England. BMJ 2013; 347:f6099.
18. Lindqvist P, Dahlbäck B, Marŝál K. Thrombotic risk during pregnancy: a population study. Obstet
Gynecol 1999; 94:595.
19. Norgren L, Austrell C, Nilsson L. The effect of graduated elastic compression stockings on femoral
blood flow velocity during late pregnancy. Vasa 1995; 24:282.
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20. Friederich PW, Sanson BJ, Simioni P, et al. Frequency of pregnancy-related venous thromboembolism
in anticoagulant factor-deficient women: implications for prophylaxis. Ann Intern Med 1996; 125:955.

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GRAPHICS

ACOG recommended thromboprophylaxis for pregnancies complicated by

inherited thrombophilias*

Clinical scenario Antepartum management Postpartum management

Lower-risk thrombophilia ¶ without Surveillance without anticoagulation Postpartum anticoagulation therapy

previous VTE therapy for patients with additional risks
factors Δ

Low-risk thrombophila with a family Surveillance without anticoagulation Postpartum anticoagulation therapy
history (first-degree relative) of VTE therapy or intermediate-dose ◊ LMWH/UFH

Low-risk thrombophilia ¶ with a Prophylactic or intermediate-dose Postpartum anticoagulation therapy

single previous episode of VTE - not LMWH/UFH or surveillance without or intermediate-dose LMWH/UFH
receiving long-term anticoagulation anticoagulation therapy
therapy

High-risk thrombophilia § without Surveillance without anticoagulation Postpartum anticoagulation therapy

previous VTE therapy, or prophylactic LMWH or
UFH

High-risk thrombophilia § with a Prophylactic, intermediate-dose, or Postpartum anticoagulation therapy,

single previous episode of VTE or an adjusted-dose LMWH/UFH regimen or intermediate or adjusted-dose
affected first-degree relative - not LMWH/UFH for six weeks (therapy
receiving long-term anticoagulation level should be at least as high as
therapy antepartum treatment)

No thrombophilia with previous Surveillance without anticoagulation Postpartum anticoagulation therapy ¥

single episode of VTE associated with therapy
transient risk factor that is no longer
present - excludes pregnancy- or
estrogen-related risk factor

No thrombophilia with previous Prophylactic-dose LMWH or UFH ¥ Postpartum anticoagulation therapy

single episode of VTE associated with
transient risk factor that was
pregnancy- or estrogen-related

No thrombophilia with previous Prophylactic-dose LMWH or UFH ¥ Postpartum anticoagulation therapy

single episode of VTE without an
associated risk factor (idiopathic) -
not receiving long-term
anticoagulation therapy

Thrombophilia or no thrombophilia Prophylactic or therapeutic-dose Postpartum anticoagulation therapy

with two or more episodes of VTE - LMWH OR
not receiving long-term OR Therapeutic-dose LMWH/UFH for six
anticoagulation therapy
Prophylactic or therapeutic-dose UFH weeks

Thrombophilia or no thrombophilia Therapeutic-dose LMWH or UFH Resumption of long-term

with two or more episodes of VTE - anticoagulation therapy
Receiving long-term anticoagulation
therapy

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 elsewhere.
¶ Low-risk thrombophilia: factor V Leiden heterozygous; prothrombin G20210A heterozygous; protein C or protein S
deficiency.
Δ First-degree relative with a history of a thrombotic episode before age 50 years, or other major thrombotic risk factors
(eg, obesity, prolonged immobility).
◊ Intermediate dosing is variably defined in the literature. The American College of Chest Physicians has defined it as a
pregnancy LMWH regimen of enoxaparin 40 mg or dalteparin 5000 units given every 12 hours. In UpToDate, intermediate
dosing refers to prophylactic LMWH dosing that is increased as the pregnancy progresses and the patient's weight
increases, up to a maximum dose of enoxaparin 1 mg/kg once daily.
§ High-risk thrombophilia: antithrombin deficiency; double heterozygous for prothrombin G20210A mutation and factor V

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Leiden; factor V Leiden homozygous or prothrombin G20210A mutation homozygous.
¥ Surveillance without anticoagulation therapy is supported as an alternative approach by some experts.

Reproduced with permission from: ACOG Practice Bulletin #138. Thromboembolism in pregnancy. Obstet Gynecol 2013;
122:706. DOI: 10.1097/01.AOG.0000433981.36184.4e. Copyright © 2013 American College of Obstetricians and
Gynecologists. Unauthorized reproduction of this material is prohibited.

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Use of heparins during pregnancy

Heparin Dose level Dosage

LMW heparin Prophylactic* Enoxaparin 40 mg SC once daily

Dalteparin 5000 units SC once daily

Intermediate ¶ Enoxaparin 40 mg SC once daily, increase as pregnancy progresses

to 1 mg/kg once daily

Dalteparin 5000 units once daily, increase as pregnancy progresses

to 100 units/kg once daily

Therapeutic Enoxaparin 1 mg/kg every 12 hours

Dalteparin 100 units/kg every 12 hours

Unfractionated Prophylactic 5000 units SC twice daily

heparin
Intermediate ¶ First trimester: 5000 to 7500 units every 12 hours

Second trimester: 7500 to 10,000 units every 12 hours

Third trimester: 10,000 units every 12 hours

Therapeutic Dose every 12 hours to keep aPTT at 1.5 to 2.5 times control or
patient's baseline six hours after dose

Doses apply to pregnant women receiving heparin for venous thromboembolism prophylaxis. Therapeutic dose
level refers to doses used both for prophylaxis in individuals at especially high risk and for treatment of venous
thromboembolism. This dosing table should not be used in women with prosthetic heart valves. Refer to the
UpToDate topic on anticoagulant use in pregnancy for details of administration and monitoring. Refer to UpToDate
topics on specific pregnant patient populations for other dosing recommendations (eg, prosthetic heart valve,
atrial fibrillation, treatment of deep vein thrombosis or pulmonary embolism).

LMW: low molecular weight; SC: subcutaneously; aPTT: activated partial thromboplastin time.
* Prophylactic dosing may require modifications for extremes of body weight; refer to the UpToDate table on LMW heparin
dosing in obesity for details.
¶ Our "intermediate" dose level differs from that used in society guidelines (eg, ACCP, ACOG).

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Contributor Disclosures
David R Schwartz, MD Nothing to disclose Atul Malhotra, MD Nothing to disclose Steven E Weinberger,
MD Nothing to disclose Lawrence LK Leung, MD Nothing to disclose Charles J Lockwood, MD,
MHCM Consultant/Advisory Boards: Celula [Aneuploidy screening (No current products or drugs in the
US)]. Jess Mandel, MD Nothing to disclose Geraldine Finlay, MD Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
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