Venous thromboembolism in pregnancy and postpartum: Prevention

INTRODUCTION — 

Pregnancy and the postpartum period are well-established risk factors for deep vein thrombosis and pulmonary embolism, which are collectively referred to as venous thromboembolism (VTE).

This topic discusses patient selection, methods, and duration of thromboprophylaxis during pregnancy and postpartum. Our approach is generally consistent with several international guidelines on selection criteria for pharmacologic thromboprophylaxis during pregnancy [1-3]. However, guidelines vary greatly and recommendations are often opinion-based due to the paucity of data in this population.

Other related topics are discussed separately:

●(See "Anticoagulation during pregnancy and postpartum: Agent selection and dosing".)

●(See "Deep vein thrombosis in pregnancy: Clinical presentation and diagnosis" and "Pulmonary embolism in pregnancy: Clinical presentation and diagnosis".)

●(See "Venous thromboembolism in pregnancy and postpartum: Treatment".)

●(See "Venous thromboembolism in pregnancy: Epidemiology, pathogenesis, and risk factors".)

●(See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults" and "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients".)

INITIAL ASSESSMENT — 

As pregnancy and postpartum are well-established risk factors for VTE, we assess all individuals for their risk of VTE and bleeding either early in pregnancy or prior to conception [2]. We reassess patients throughout pregnancy as needed, for example, when complications arise (eg, preeclampsia) and during transition periods (ie, pregnancy to postpartum, outpatient to inpatient setting).

VTE risk — Assessment for VTE risk typically includes the following:

●Previous history of VTE and any provoking event (eg, surgery, use of a combined estrogen-progestin oral contraceptive, pregnancy)

●Family history of VTE

●Known diagnosis of an inherited thrombophilic disorder (eg, factor V Leiden mutation, prothrombin gene mutation, protein S or C deficiency, antithrombin deficiency)

●Known diagnosis of antiphospholipid syndrome (APS) or suspicion of APS in the setting of recurrent pregnancy loss

●Coexisting medical conditions that may contribute to VTE risk (eg, heart disease, sickle cell anemia, inflammatory bowel disease, kidney and liver disease, systemic lupus erythematosus, type 1 diabetes mellitus)

●Medication history (including medications for in vitro fertilization)

●Cigarette smoking

●Obesity

●Varicose veins

●Prolonged immobilization (eg, >3 days [inpatient] or >7 days [outpatient])

Risk factors for VTE are presented in the table (table 1) and discussed in more detail separately. (See "Overview of the causes of venous thrombosis in adults".)

Most patients with risk factors for VTE do not require subspecialty evaluation; an exception is patients in whom an inherited or acquired thrombophilia is suspected and those in whom the risk is unclear. These patients are discussed separately. (See "Inherited thrombophilias in pregnancy", section on 'Selection of patients for testing' and "Antiphospholipid syndrome: Diagnosis", section on 'Diagnostic evaluation'.)

Bleeding risk — When pharmacologic thromboprophylaxis is indicated, we also assess each patient for the risk of bleeding.

The risk of bleeding with pharmacologic prophylaxis is increased in patients with nonpregnancy-related factors (eg, bleeding diathesis, kidney or liver disease) and pregnancy-related factors (eg, uncontrolled hypertension, vaginal or cesarean birth, placental abruption, placenta previa, expanding subchorionic hematoma). This is discussed separately. (See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults", section on 'Bleeding risk assessment' and "Venous thromboembolism in pregnancy and postpartum: Treatment", section on 'Assess bleeding risk'.)

Institutional protocols and assessment tools — We encourage the development and use of institutional protocols to help clinicians select patients with VTE for thromboprophylaxis.

While several international societies have proposed tools that assess the risk of VTE during pregnancy and postpartum [1,4-6], we do not typically use these tools. None are prospectively validated in this population, nor do they incorporate all potential risk factors (eg, inpatient versus outpatient status). In addition, most have developed their scoring system using the relative risk of VTE (rather than absolute risk) and do not determine if risk factors are additive, neutral, or synergistic. Data suggest that applying these recommendations to cohorts of pregnant and postpartum individuals generates wide ranges in the potential rates of thromboprophylaxis from 7 to 40 percent [7,8].

GENERAL MEASURES FOR ALL PATIENTS — 

General measures for all patients include ambulation and, when possible, left-lateral decubitus positioning during late pregnancy to minimize inferior vena cava compression.

Graduated compression stockings (GCS) may be useful in patients with post-thrombotic syndrome to help reduce edema or to relieve symptoms of venous insufficiency.

We do not use GCS as a primary VTE prevention measure in patients at high risk for VTE unless there are contraindications to pharmacologic thromboprophylaxis. (See 'Patients at high risk of bleeding: Mechanical prophylaxis' below.)

PHARMACOLOGIC PROPHYLAXIS FOR OUTPATIENTS AT HIGH RISK OF VTE — 

Most pregnant individuals do not require pharmacologic thromboprophylaxis during pregnancy or postpartum. Rather, pharmacologic prophylaxis is administered to a select group of patients considered to be at high risk of VTE. Selecting these patients can be challenging, as pregnancy and the postpartum period also contribute to the risk of VTE, and data in this population are limited. Consequently, we often advocate for a multidisciplinary approach, especially when the risk is unclear (eg, with specialists from obstetrics and gynecology, hematology, pulmonology).

Identifying patients at highest risk

History of VTE (unprovoked, estrogen-associated, recurrent, persistent risk) — In our practice, we administer pharmacologic prophylaxis to individuals with a prior history of VTE with the following characteristics:

●A single episode of unprovoked VTE (ie, absence of risk factors or provoking event such as surgery)

●A single episode of estrogen-associated VTE (eg, pregnancy, oral contraception, ovarian hyperstimulation syndrome due to assisted reproductive technologies)

●Recurrent VTE (regardless of whether VTE is provoked or unprovoked)

●A single episode of VTE with persistent VTE risk factors (eg, prolonged immobility, active cancer)

The evidence to support pharmacologic thromboprophylaxis in the indicated populations is limited since it is mostly indirect (derived from the nonpregnant population), based upon small retrospective studies of thromboprophylaxis in high-risk pregnant patients [1,2,9-19], one large randomized trial that compared high- with low-dose heparin [20] (see "Anticoagulation during pregnancy and postpartum: Agent selection and dosing", section on 'Low and intermediate dose (used for VTE prophylaxis)'), and our clinical experience. These data suggest that VTE risk in pregnant patients with a prior episode of VTE ranges from 2.5 to 11 percent [9-12]. Risk is on the higher end of this range in those with unprovoked VTE, recurrent VTE, and VTE related to pregnancy or hormone use and on the lower end when VTE is provoked by a major event (eg, surgery, trauma). Thromboprophylaxis in patients with prior provoked VTE is discussed below. (See 'History of VTE (provoked)' below.)

Selected inherited thrombophilias — Patients with selected inherited thrombophilias (eg, factor V Leiden mutation, prothrombin gene mutation, protein S or C deficiency, antithrombin deficiency) who become pregnant have an increased risk of VTE. However, not every patient with an inherited thrombophilic disorder requires pharmacologic thromboprophylaxis during pregnancy or postpartum since VTE risk varies among "high-risk" and "low-risk" thrombophilias (table 2). Thus, patients with inherited thrombophilias are often managed in conjunction with a hematologist to determine which individuals require thromboprophylaxis.

Patient selection for thromboprophylaxis in inherited thrombophilias is discussed in detail separately. (See "Inherited thrombophilias in pregnancy", section on 'Prevention of VTE'.)

Antiphospholipid syndrome — Antiphospholipid syndrome, an acquired thrombophilia, confers a high risk of both venous and arterial embolism. The risk increases with the number of positive antiphospholipid antibody tests (highest in those who are triple antibody positive) and the magnitude of antibody titers [21,22]. The approach is outlined in the table (table 3) and algorithm (algorithm 1) and is discussed separately. (See "Antiphospholipid syndrome: Obstetric implications and management in pregnancy".)

Identifying other at-risk patients

History of VTE (provoked) — Our approach in patients with a history of provoked VTE depends upon the presence of persistent risk factors:

●For patients with a previous episode of provoked VTE (eg, surgery, trauma) and persistent risk factors (eg, immobilization or paralysis, obesity, low-risk thrombophilia), we administer pharmacologic prophylaxis during pregnancy and postpartum. Such patients have an elevated risk of VTE recurrence throughout pregnancy and postpartum. (See "Venous thromboembolism in pregnancy: Epidemiology, pathogenesis, and risk factors", section on 'Risk factors'.)

●By contrast, for patients with a previous episode of provoked VTE but no additional risk factors for VTE, we typically administer pharmacologic prophylaxis only during the postpartum period. While such patients have an overall lower risk of recurrence than those with persistent risk factors, the risk is highest in the postpartum period. However, guidance varies with some guidelines suggesting initiating thromboprophylaxis sooner (eg, after 28 weeks) [5].

Evidence to support this practice is discussed above. (See 'History of VTE (unprovoked, estrogen-associated, recurrent, persistent risk)' above.)

Other — We exercise clinical judgment and individualize the decision to administer pharmacologic thromboprophylaxis when other risk factors are present in isolation. The threshold to administer pharmacologic thromboprophylaxis is lowered when multiple risk factors are present. As examples:

●Obesity – While obesity (defined as body mass index [BMI] >30 kg/m²) is an independent risk factor for VTE, the BMI at which to administer thromboprophylaxis is unclear. As a general guide, we consider a BMI >40 kg/m² or a BMI >30 but <40 kg/m² plus another risk factor as an indication for thromboprophylaxis.

In one case-control study including almost 130 cases of VTE in pregnancy and postpartum, antenatal and postnatal VTE rates were increased almost 10- and threefold, respectively, in those with a BMI >30 kg/m² [23]. However, other data suggest that excluding patients with obesity from thromboprophylaxis protocols may not impact VTE rates [24].

●Prolonged immobilization (eg, >7 days) – Limited data suggest a sevenfold increase in VTE risk when antepartum patients are immobilized for >7 days (as an outpatient) [25,26].

●Multiple risk factors – The presence of multiple risk factors for VTE (having two or more medical conditions associated with increased VTE risk; eg, immobilization plus obesity), other than those listed above (see 'Identifying patients at highest risk' above), is associated with a high risk of VTE. For example, the odds of VTE in patients with obesity are further increased when patients are immobile for >7 days (adjusted odds ratio 62.3 for antenatal VTE and 40 for postnatal VTE) [25].

However, quantifying the risk in other patients is more challenging and the optimal number of risk factors that justify thromboprophylaxis is unknown.

Timing and duration of prophylaxis

●Highest-risk patients – In the highest-risk patients (see 'Identifying patients at highest risk' above), we initiate thromboprophylaxis once the diagnosis of pregnancy is made and continue it throughout pregnancy and for at least six weeks postpartum, provided the risk of bleeding is assessed as low [1,27]. This is consistent with guidance from the 2012 American College of Chest Physicians clinical practice guidelines [1]. For those at greatest risk (eg, history of unprovoked VTE and persistent risk factors for thrombosis), thromboprophylaxis is sometimes extended for a longer duration (eg, up to three months following birth).

●Other at-risk patients – In other at-risk patients (see 'Identifying other at-risk patients' above), the ideal duration and timing are unknown. Thus, the need for outpatient antepartum and/or postpartum prophylaxis should be individualized. In general, the threshold for thromboprophylaxis is lower postpartum than antepartum since the risk of VTE is greatest postpartum and the potential for obstetric-associated hemorrhage is lower. (See "Inherited thrombophilias in pregnancy", section on 'Prevention of VTE' and "Deep vein thrombosis in pregnancy: Clinical presentation and diagnosis", section on 'Clinical presentation'.)

Role of baseline compression ultrasound — In patients with a prior deep vein thrombosis, we perform a baseline compression ultrasound (CUS) of the previously affected leg to facilitate interpretation of any subsequent CUS studies. We consider this reasonable since CUS interpretation is complex and more readily identifies new thrombus when baseline findings have been documented. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'Ultrasonography interpretation'.)

PHARMACOLOGIC PROPHYLAXIS FOR INPATIENTS AT HIGH RISK OF VTE

Patients receiving outpatient thromboprophylaxis — Patients who are already receiving outpatient thromboprophylaxis should be reassessed for the need for inpatient thromboprophylaxis at the beginning of hospital admission. In most patients, thromboprophylaxis is continued provided the bleeding risk is unchanged. (See 'Pharmacologic prophylaxis for outpatients at high risk of VTE' above.)

Patients admitted for nondelivery issues

●Patient selection – Selecting inpatients who require VTE prophylaxis during hospital admission can be challenging. As a general rule, it applies to inpatients who would under nonpregnancy circumstances require VTE prophylaxis during hospital admission. Examples of such patients may include, but are not limited to, those with the following [23,25,28-32]:

•Critical illness (eg, sepsis) (see "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults")

•Nonobstetric surgery (see "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients" and "Prevention of venous thromboembolism in adults undergoing hip fracture repair or hip or knee replacement")

•Orthopedic injury (see "Prevention of venous thromboembolism (VTE) in adults with non-major extremity orthopedic injury with or without surgical repair")

•Inpatient stay >3 days

Examples of admission for pregnancy-related conditions that may require pharmacologic thromboprophylaxis include the following:

•Hyperemesis (see "Nausea and vomiting of pregnancy: Treatment and outcome", section on 'Role of thromboprophylaxis')

•Preeclampsia (see "Preeclampsia: Intrapartum and postpartum management and long-term prognosis", section on 'Venous thromboembolism prophylaxis')

Limited data support this approach, and additional studies are needed to accurately identify at-risk patients who would benefit from anticoagulant thromboprophylaxis:

•In a national database analysis of over 245,000 pregnant patients, hospital admission for nondelivery reasons compared with time spent outside of the hospital was associated with a risk of VTE that was 18-fold higher during hospitalization (absolute rate 1752 versus 97 per 100,000 person-years) and over sixfold higher during the 28 days after discharge (676 per 100,000 person-years) [29]. The highest rates were observed in those with a body mass index (BMI) >30 kg/m², maternal age >35 years, admission during the third trimester, and hospital stay >3 days.

•A single-center, observational study of over 17,000 postpartum patients compared a selective protocol with an older, less selective protocol for postpartum pharmacologic VTE prophylaxis [24].

-In the less selective protocol, enoxaparin was administered to patients who received antepartum outpatient prophylaxis and those with a prepregnancy BMI ≥40 kg/m², a history of prior VTE, a low- or high-risk thrombophilia, or two or more additional risk factors or medical conditions.

-In the more selective protocol, enoxaparin was administered to patients who received antepartum outpatient prophylaxis and those with a prior history of VTE, nephrotic syndrome, or three or more additional risk factors or medical conditions.

With the more selective protocol, rates of chemoprophylaxis were halved. In addition, rates of wound hematomas were lower (0.3 versus 0.7 percent, adjusted odds ratio 0.38, 95% CI 0.21-0.67), especially superficial hematomas, while rates of VTE were unchanged (0.1 percent each). Limitations of this study are its retrospective design and differences in baseline patient characteristics (more patients in the more selective group were older and had comorbidities).

●Duration of prophylaxis – When thromboprophylaxis is administered only during hospitalization, it should continue until the patient is ambulatory and is then generally discontinued, provided that there is no indication for outpatient thromboprophylaxis.

Extended prophylaxis (ie, after discharge) is considered by some clinicians to be beneficial in select circumstances (eg, a patient who is assessed to be at very high risk or who has multiple persistent additional risk factors for VTE) [1].

Cesarean birth — Only select high-risk patients undergoing cesarean birth require pharmacologic thromboprophylaxis. Patient selection and type of thromboprophylaxis used are discussed in detail separately. (See "Cesarean birth: Preincision planning and patient preparation", section on 'Thromboembolism prophylaxis'.)

CHOICE OF ANTICOAGULANT AND DOSING — 

Choice of anticoagulant (eg, low molecular weight heparin, unfractionated heparin) and dosing during pregnancy and postpartum are reviewed in the table (table 4) and discussed separately. (See "Anticoagulation during pregnancy and postpartum: Agent selection and dosing".)

SPECIAL POPULATIONS

Patients at high risk of bleeding: Mechanical prophylaxis — If the patient's bleeding risk is high (see 'Bleeding risk' above), we use mechanical methods (eg, intermittent pneumatic compression devices or, alternatively, graduated compression stockings). Indirect data in nonpregnant patients support the use of mechanical methods of thromboprophylaxis during pregnancy and postpartum. These data are discussed separately. (See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults", section on 'Mechanical methods of thromboprophylaxis'.)

Once bleeding risk decreases to an acceptable level, pharmacologic thromboprophylaxis can begin (or resume). Some experts use unfractionated heparin in these circumstances since it has a shorter half-life than low molecular weight (LMW) heparin and can be reversed (with protamine sulfate) if needed for significant bleeding.

Patients receiving therapeutic anticoagulation — For patients who are already receiving therapeutic oral anticoagulation and become pregnant, we convert them to a heparin-based regimen, typically LMW heparin. Switching anticoagulants during pregnancy is discussed in more detail separately. (See "Anticoagulation during pregnancy and postpartum: Agent selection and dosing", section on 'Switching from oral anticoagulants to LMW heparin'.)

If therapeutic anticoagulant therapy is administered for VTE during pregnancy, we reassess the need for prophylaxis once the predetermined duration of anticoagulant therapy is over using data outlined in this topic. (See 'Pharmacologic prophylaxis for outpatients at high risk of VTE' above and 'Pharmacologic prophylaxis for inpatients at high risk of VTE' above.)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism" and "Society guideline links: Anticoagulation in pregnancy".)

SUMMARY AND RECOMMENDATIONS

●Initial assessment – We assess all individuals for their risk of venous thromboembolism (VTE) and bleeding prior to conception (if feasible) or early in pregnancy and again throughout pregnancy as needed (eg, when complications arise or during transition phases of pregnancy or changing to inpatient status). Important VTE risk factors common during pregnancy are listed above (see 'VTE risk' above); these and other risk factors are included in the table (table 1). (See 'Initial assessment' above.)

●Most patients and general measures – For most nonhospitalized pregnant patients, we suggest general measures rather than pharmacologic VTE prophylaxis (Grade 2C). General measures for all patients include ambulation and, when possible, left-lateral decubitus positioning during late pregnancy to minimize inferior vena cava compression.

●Outpatient pharmacologic prophylaxis for patients at high risk – Pharmacologic prophylaxis is administered to those at high risk of VTE unless they are at high risk for bleeding.

•History of VTE – For patients with a prior history of VTE and high-risk characteristics, we suggest outpatient pharmacologic thromboprophylaxis rather than general measures alone (Grade 2C). High-risk characteristics include (see 'Identifying patients at highest risk' above):

-A single episode of unprovoked VTE (ie, absence of risk factors or provoking event such as surgery)

-A single episode of estrogen-associated VTE (eg, pregnancy, oral contraception, ovarian hyperstimulation syndrome due to assisted reproductive technologies)

-Recurrent VTE (regardless of whether VTE is provoked or unprovoked)

-A single episode of VTE with persistent risk factors (eg, immobility, cancer)

Available data are limited and suggest that VTE risk in pregnant patients with a prior episode of VTE ranges from 2.5 to 11 percent. Risk is on the higher end of this range in those with unprovoked VTE, recurrent VTE, and VTE related to pregnancy or hormone use and on the lower end when VTE is provoked by a major event (eg, surgery, trauma).

In such patients, we initiate thromboprophylaxis once the diagnosis of pregnancy is made and continue it throughout pregnancy and for at least six weeks postpartum, provided the risk of bleeding is assessed as low. In some patients (eg, history of unprovoked VTE and persistent risk factors for thrombosis), prophylaxis is sometimes extended for a longer duration (eg, up to three months following birth). (See 'Timing and duration of prophylaxis' above.)

•Thrombophilia and antiphospholipid antibodies/syndrome – Other high-risk groups in whom pharmacologic prophylaxis or therapeutic anticoagulation are also considered include select patients with a thrombophilia disorder (table 2) and patients with antiphospholipid antibodies or syndrome (table 3). These patients are often managed in conjunction with a hematologist and are discussed in detail separately. (See "Inherited thrombophilias in pregnancy", section on 'Prevention of VTE' and "Antiphospholipid syndrome: Obstetric implications and management in pregnancy".)

•Other risk factors – In patients with other risk factors (eg, a history of provoked VTE [surgery, trauma], obesity, prolonged immobilization), we individualize the decision to administer pharmacologic thromboprophylaxis. The threshold to administer pharmacologic thromboprophylaxis is lowered when multiple risk factors are present. The ideal timing and duration are unknown and should be individualized. In general, the threshold for thromboprophylaxis is lower postpartum than antepartum since the risk of VTE is greatest postpartum and the potential for obstetric-associated hemorrhage is lower. (See 'Identifying other at-risk patients' above and 'Timing and duration of prophylaxis' above.)

●Inpatient pharmacologic prophylaxis for patients at high risk

•For patients who are already receiving outpatient thromboprophylaxis, we continue it, provided the bleeding risk is unchanged. (See 'Patients receiving outpatient thromboprophylaxis' above.)

•For most pregnant patients who are hospitalized antenatally for nondelivery reasons, we administer thromboprophylaxis using the same criteria as for nonpregnant patients. Examples include critical illness, nonobstetric surgery, orthopedic injury, inpatient stay >3 days, hyperemesis, and preeclampsia. While data are limited, indirect data from nonpregnant patients suggest that rates of VTE may be sufficiently high to justify thromboprophylaxis in such patients. (See 'Patients admitted for nondelivery issues' above.)

•Only select high-risk patients undergoing cesarean birth require pharmacologic thromboprophylaxis. Further details are provided separately. (See "Cesarean birth: Preincision planning and patient preparation", section on 'Thromboembolism prophylaxis'.)

●Agent choice – Choice of anticoagulant (eg, low molecular weight heparin, unfractionated heparin) and dosing during pregnancy and postpartum are reviewed in the table (table 4) and discussed separately. (See "Anticoagulation during pregnancy and postpartum: Agent selection and dosing".)

●Patients at high risk of bleeding – For pregnant or postpartum patients in whom the bleeding risk is high, we suggest mechanical methods rather than pharmacologic prophylaxis (Grade 2C). Among the available methods, we typically use intermittent pneumatic compression devices; graduated compression stockings are an alternative. Indirect data in nonpregnant patients support the use of mechanical methods during pregnancy and postpartum. Once bleeding risk decreases to an acceptable level, pharmacologic thromboprophylaxis can begin (or resume). This is discussed separately. (See 'Special populations' above and "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults", section on 'Mechanical methods of thromboprophylaxis'.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges David R Schwartz, MD, who contributed to earlier versions of this topic review.