Deep vein thrombosis in pregnancy: Clinical presentation and diagnosis

INTRODUCTION — Pregnancy and the postpartum period are well-established risk factors for venous thromboembolism (VTE). VTE can manifest during pregnancy and postpartum as an isolated lower extremity deep vein thrombosis (DVT) or a clot can break off from the lower extremities and travel to the lung to present as a pulmonary embolism (PE), which can be life-threatening. Thus, detection of DVT during pregnancy is critical to preventing deaths from PE.

The clinical presentation and diagnosis of DVT during pregnancy and the postpartum period will be reviewed here. Other related topics are discussed separately.

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

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

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

●(See "Venous thromboembolism in pregnancy: Prevention".)

●(See "Use of anticoagulants during pregnancy and postpartum".)

CLINICAL PRESENTATION — The clinical presentation of DVT during pregnancy is similar to that in nonpregnant females; patients typically present with diffuse pain and swelling of the lower extremity that may or may not be associated with erythema, warmth, and tenderness. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

However, there are three important distinctions:

●Predominance of left lower extremity thrombosis – The majority of lower extremity DVTs in pregnant and postpartum patients are left-sided. However, if symptoms are right-sided or bilateral, it should not be assumed that a patient does not have DVT.

In one study of 60 pregnant patients with a first episode of DVT, almost all (97 percent) had isolated left lower extremity DVT; only two patients had bilateral DVTs [1]. In another retrospective study including 96 pregnant patients with DVT in whom the affected side was known, 88 percent had left-sided DVT [2].

This striking distribution has been attributed to increased venous stasis in the left leg related to compression of the left iliac vein by the right iliac artery, coupled with compression of the inferior vena cava by the gravid uterus [1,3,4]. (See "Venous thromboembolism in pregnancy: Epidemiology, pathogenesis, and risk factors", section on 'Pathogenesis' and "Overview of the causes of venous thrombosis", section on 'May-Thurner syndrome'.)

●Higher rates of pelvic vein thrombosis – Pelvic vein DVT is more commonly diagnosed in pregnant and postpartum females than in nonpregnant patients. (See "Venous thromboembolism in pregnancy: Epidemiology, pathogenesis, and risk factors", section on 'Epidemiology'.)

Symptoms of iliac vein thrombosis include swelling of the entire leg with or without flank, lower abdomen, buttock, or back pain [5,6].

●Overlapping symptoms with pregnancy – Symptoms of DVT may also overlap with features of normal pregnancy (eg, lower extremity swelling and pain; pain in the back, buttock, and flank). Thus, a high level of suspicion in this population is critical for early diagnosis. (See 'Differential diagnosis' below.)

INITIAL DIAGNOSTIC EVALUATION — Successful diagnosis of suspected DVT in pregnancy and the postpartum period requires that clinicians have a high index of clinical suspicion and low threshold for use of objective confirmatory testing with compression ultrasonography (CUS).

Several approaches to the diagnosis of DVT during pregnancy and postpartum have been described in evidence-based practice guidelines published by the American College of Chest Physicians (ACCP), the American College of Obstetricians and Gynecologists (ACOG), the American Society of Hematology (ASH), and others [7-11]. However, there is no one optimal approach. We describe two approaches: a traditional approach where CUS is performed on all suspected cases of DVT (algorithm 1) and an alternative approach based upon clinical suspicion (algorithm 2). Choosing between these approaches depends on clinician preference, resource availability, clinical suspicion, and patient preference. These options, and their advantages and disadvantages, are discussed below. (See 'Traditional approach: Compression ultrasonography' below and 'Alternative approach based on clinical suspicion' below.)

Assessing pretest probability — We typically determine the probability of DVT based on gestalt clinical suspicion. Clinical pretest probability (PTP) scoring systems (eg, Wells score, modified Wells score) are not used. Estimating the probability of DVT facilitates decisions regarding the need for CUS testing, additional imaging (eg, when CUS is indeterminate or incongruent with clinical suspicion), and empiric anticoagulation.

PTP scoring systems have been described but require additional study before use:

●LEFt clinical prediction rule – The LEFt clinical prediction rule, a pregnancy-specific PTP tool, was developed on the rationale that DVT in pregnancy is predominantly left-sided [12,13].

In a cross-sectional study that evaluated clinical assessment in predicting the presence of a suspected first-time DVT in 194 pregnant females, three objective variables were highly predictive of DVT [12]:

•Symptoms in the left leg (L for left)

•Calf circumference difference ≥2 cm (E for edema)

•First trimester presentation (Ft for first trimester)

At least one of these variables was present in all 17 patients with DVT. Among patients presenting with none, one, or two to three of these variables, DVT was diagnosed in zero, 16, and 58 percent of patients, respectively. The LEFt clinical prediction rule was further validated in a separate cohort of 157 pregnant patients with suspected DVT [13]. In this population, a negative LEFt rule (ie, score of 0) accurately identified all 46 patients who did not have a DVT.

A clinical study evaluating the combined use of the LEFt rule along with D-dimer testing to accurately exclude DVT in pregnant females is ongoing.

●Wells and modified Wells score – The Wells and modified Wells scoring systems are widely used scoring systems for nonpregnant patients with suspected DVT. However, they are not validated for use in pregnancy and are less reliable in this population than in the nonpregnant population. In addition, some of the listed features (eg, active cancer, recent surgery) are not likely to be present in young healthy pregnant females while other features (eg, pitting edema, lower extremity tenderness) are common symptoms of pregnancy, even in the absence of DVT. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

Traditional approach: Compression ultrasonography — In the traditional approach, all pregnant patients suspected of having a DVT undergo initial evaluation with CUS (algorithm 1). We prefer whole-leg CUS (images both the proximal and calf veins) rather than proximal vein CUS (does not image the calf) in this population (figure 1) [14], although choosing between them is often institution-dependent. It is therefore prudent that the clinician know which type is performed by the bedside technician.

●Advantages – Advantages of this approach are as follows:

•Proximal vein CUS is a sensitive and specific test to confirm or exclude DVT.

Poor compressibility of the femoral or popliteal vein (ie, proximal veins (figure 1)) with the ultrasound probe is highly sensitive (95 percent) and specific (>95 percent) for the diagnosis of symptomatic proximal vein thrombosis in the nonpregnant patient (see "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity"). In a retrospective study of 162 pregnant and postpartum patients that used whole-leg ultrasound, among those who had a negative initial negative initial CUS, no DVT was found during follow-up at three months [15]. Similarly, in a prospective study evaluating the diagnostic value of single complete whole-leg CUS in pregnant and postpartum patients, 2 out of 145 pregnant patients (1.4 percent) and zero out of 32 postpartum females (0 percent) with suspected DVT and a single negative CUS had DVT during three months of follow-up [16].

•When CUS is available, it can often be performed quickly (eg, typically within an hour) and access to results is usually immediate.

•It is noninvasive and not associated with radiation toxicity. (See 'Radiation and contrast exposure' below.)

●Disadvantages – Disadvantages of this approach are as follows:

•Immediate access to CUS, particularly for outpatient evaluation or evaluation at night or during the weekend, is not universally available.

•Expertise is needed to perform and interpret the test.

•If proximal vein (rather than whole-leg) CUS is used, clinicians should be aware that it is less sensitive for the diagnosis of pelvic vein thrombosis and for calf vein thrombosis [17]. Options when these diagnoses are suspected and proximal vein CUS is negative are discussed below. (See 'Negative CUS congruent with low or moderate clinical suspicion' below.)

•The approach also likely results in overuse of ultrasonography in a population where most test results will be negative.

In advanced pregnancy, CUS should be performed with the patient in the left lateral decubitus position to improve the detection of iliac vein thrombosis, which is more common in pregnant than nonpregnant females. (See 'Clinical presentation' above and "Venous thromboembolism in pregnancy: Epidemiology, pathogenesis, and risk factors", section on 'Pelvic thrombosis'.)

Alternative approach based on clinical suspicion — As an alternative approach in patients with a low or moderate clinical suspicion, a negative D-dimer may be used to exclude DVT and avoid imaging with CUS (algorithm 2). This approach may be more useful during the first or second trimester when the proportion of pregnant females who have a negative D-dimer level is higher than in the third trimester or in facilities that do not have immediate access to CUS. All other patients should undergo CUS as described above. (See 'Traditional approach: Compression ultrasonography' above.)

●Advantages – Advantages of obtaining a D-dimer are that the result is easy to interpret (either positive [≥ threshold cutoff] or negative [< threshold cutoff]) and over-testing is avoided since it is more selective in choosing patients who undergo CUS.

A negative D-dimer has a high negative predictive value in nonpregnant patients with suspected venous thromboembolism (VTE). In pregnant patients, a negative D-dimer has also proved useful in ruling out pulmonary embolism (PE). (See "Pulmonary embolism in pregnancy: Clinical presentation and diagnosis", section on 'D-dimer' and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

Data support the use of a negative D-dimer test to exclude DVT in pregnant patients with a low or moderate PTP of DVT. In a meta-analysis of four cohort studies including 312 pregnant patients with suspected VTE who did not receive anticoagulation based on a negative D-dimer result, only one patient (0.32 percent) developed VTE during the following three-month period [18]. The pooled estimates for sensitivity and negative predictive value were 99.5 and 100 percent, respectively.

●Disadvantages

•D-dimer becomes less useful with gestational age and many patients will still require ultrasonography.

D-dimer levels increase during the course of a normal pregnancy and slowly decline postpartum, rendering D-dimer less specific than in nonpregnant patients, particularly when traditional cutoff values (eg, <500 ng/mL) are used [19-24]. In a study of 50 pregnant patients without VTE, D-dimer levels increased with each trimester such that 22 percent of patients in the second trimester and none in the third trimester had a normal D-dimer concentration (ie, <500 ng/mL) [20]. In another study of 149 consecutive pregnant patients in whom DVT was ruled out by CUS, D-dimer was negative in 100 percent in the first trimester, 76 percent in the second trimester, and 49 percent in the third trimester [21]. D-dimer was positive in 0 percent (first trimester), 24 percent (second trimester), and 51 percent (third trimester) of patients.

•There is no agreed-upon pregnancy-adjusted reference range or single cutoff. Although preliminary data reported maintenance of high sensitivity (80 to 100 percent) and improved specificity (62 to 79 percent) of D-dimer for DVT diagnosis when higher cutoff values were used [22,23], further studies are needed before this approach can be routinely used. Until robust data support an ideal cutoff value, we use the traditional cutoff value of 500 ng/mL.

Low or moderate clinical suspicion: D-dimer — In pregnant or postpartum patients with a low or moderate clinical suspicion for DVT (see 'Assessing pretest probability' above), a D-dimer level can be obtained.

●For patients in whom the D-dimer level is negative (eg, <500 ng/mL by high sensitivity assay), CUS is not necessary; patients should be observed clinically and asked to return immediately for any progressive signs or symptoms of DVT. (See 'Clinical presentation' above and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'Clinical presentation'.)

●For patients in whom the D-dimer level is positive (eg, ≥500 ng/mL by high sensitivity assay), proximal CUS should be performed. (See 'Traditional approach: Compression ultrasonography' above.)

High clinical suspicion: Compression ultrasound — For patients with a high clinical suspicion for DVT during pregnancy, CUS should be performed without obtaining a D-dimer level. We have a preference for whole-leg CUS, although institutional practice may vary (see 'Traditional approach: Compression ultrasonography' above). If a delay in obtaining CUS is anticipated, we also administer empiric anticoagulation in this subgroup (unless there is a contraindication). Data to support this approach is described separately. (See "Venous thromboembolism in pregnancy and postpartum: Treatment", section on 'Empiric therapy' and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

Role of laboratory testing — Routine laboratory tests (eg, complete blood count, chemistries, liver function tests, coagulation studies) are not useful diagnostically but may provide clues regarding the underlying cause and may be useful for therapeutic decisions.

Measuring peripheral oxygen saturation is prudent, and if low, it may indicate concurrent PE. (See "Pulmonary embolism in pregnancy: Clinical presentation and diagnosis", section on 'Oxygenation measures'.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of DVT during pregnancy and the postpartum period is similar to that in nonpregnant patients, with the added condition of pregnancy itself since some features of pregnancy overlap with those of DVT (eg, swelling and tenderness of the lower extremity; lower back, buttock, or flank pain). The differential diagnosis of DVT is discussed separately. (See "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes" and "Clinical manifestations and diagnosis of early pregnancy", section on 'Clinical manifestations of early pregnancy' and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

DVT can also coexist with other conditions. As an example, the finding of an alternative diagnosis (eg, cellulitis) will lower the clinical suspicion for DVT, but does not always obviate the need for diagnostic imaging.

In most cases, compression ultrasonography helps narrow the differential diagnosis. (See 'Traditional approach: Compression ultrasonography' above.)

NEED FOR SUBSEQUENT TESTING — The need for additional testing (eg, Doppler ultrasound of the iliac vein, magnetic resonance (MR) or contrast venography, serial compression ultrasonography [CUS]) is dependent on the initial CUS result and clinical suspicion for proximal vein, pelvic vein, or calf vein DVT (algorithm 1).

Positive CUS — A positive CUS is diagnostic of DVT. Treatment should be initiated immediately; this is discussed in detail separately. (See "Venous thromboembolism in pregnancy and postpartum: Treatment".)

Negative CUS congruent with low or moderate clinical suspicion — If CUS is negative and congruent with a low to moderate clinical suspicion, we do not typically perform additional testing. However, we have a low threshold to order additional testing (eg, serial CUS) for those in whom clinical suspicion is in the moderate range or in whom only proximal vein rather than whole-leg CUS was performed. We also follow patients clinically for any signs of DVT as the pregnancy progresses. (See 'Clinical presentation' above and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'Clinical presentation'.)

Negative CUS incongruent with clinical suspicion — When the initial CUS is negative, but clinical suspicion for DVT remains, two decisions need to be made:

●What additional tests should be performed?

●Should the patient be treated with empiric anticoagulation while awaiting testing?

There is a paucity of data to guide these decisions. Rather, clinicians are reliant on their judgment, the strength of their clinical suspicion, suspicion for calf vein DVT (also known as distal DVT) or iliac vein thrombosis, possibility of a false negative or an inconclusive study, and the risk of untreated venous thromboembolism and bleeding (algorithm 1). Our approach in this population is outlined in this section.

Calf vein DVT suspected

Preferred: Serial compression ultrasound — For pregnant patients in whom the initial proximal vein CUS is negative and in whom there is clinical suspicion for calf vein DVT, we perform CUS on day 3 and 7 without empiric anticoagulation. Notably, the suspicion for calf vein DVT should be very low if initial whole-leg CUS was negative; the clinician should use their judgment as to whether the CUS needs to be repeated (eg, inconclusive study). Empiric anticoagulation is discussed separately. (See "Venous thromboembolism in pregnancy and postpartum: Treatment", section on 'Empiric therapy' and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

If DVT is found on serial imaging, treatment is indicated. If DVT is not found, further testing is not necessary; patients should be observed clinically and asked to return immediately for any progressive signs or symptoms of DVT. (See 'Clinical presentation' above and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'Clinical presentation'.)

Data in pregnant patients that support serial CUS (performed on days 3 and 7) and withholding anticoagulation are limited. However, this approach has been well validated in nonpregnant patients with suspected DVT for the detection of calf vein DVT in the setting of an initially negative ultrasound (see "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Distal DVT'). In pregnant and postpartum patients, a number of small prospective studies similarly suggest that the follow-up rate of DVT is low (eg, <2 percent) and that serial imaging without anticoagulation is a safe approach [7,15,21,25,26]. As examples:

●In a single center, prospective study of 221 patients with suspected DVT and initial negative ultrasound, serial proximal vein CUS (days 3 and 7) excluded DVT at three months with a sensitivity and negative predictive value of 94.1 and 99.5 percent, respectively [25].

●In an observational study including 55 patients with an initial negative whole-leg ultrasound, ultrasound examination after seven days remained negative; among the patients who returned for their six-week postpartum visit (78 percent of patients), none experienced a thromboembolic event [26].

Alternatives — Alternatively, if serial CUS is not feasible, the following are options:

●A D-dimer level may be measured (if not already done) to exclude DVT, if negative. However, a positive D-dimer cannot be used to confirm the presence of DVT. (See 'Low or moderate clinical suspicion: D-dimer' above.)

●Whole-leg CUS can be performed, if available and not already done. (See 'High clinical suspicion: Compression ultrasound' above.)

Use of whole-leg CUS may aid in the detection of calf vein DVT and although preferred, is not universally performed. If calf vein DVT is found on whole-leg CUS, we generally administer anticoagulant therapy, the details of which are discussed separately. (See "Venous thromboembolism in pregnancy and postpartum: Treatment", section on 'Distal DVT and small subsegmental PE'.)

Iliac vein thrombosis suspected — For pregnant or postpartum patients in whom the initial CUS was negative but there is clinical suspicion for iliac vein thrombosis, we usually evaluate further with Doppler ultrasound directed at the iliac vein.

MR venography is an alternative if Doppler ultrasonography is unrevealing and suspicion remains.

Ascending contrast venography is rarely needed and is becoming obsolete.

For all patients in whom an iliac vein thrombosis is suspected, we suggest empiric anticoagulation while waiting for the subsequent test result. Empiric anticoagulation is discussed separately. (See "Venous thromboembolism in pregnancy and postpartum: Treatment", section on 'Empiric therapy' and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

Preferred: Doppler ultrasonography — The addition of Doppler analysis of flow variation with respiration assists in diagnosing isolated iliac vein thrombosis; the test is performed with the patient in the left lateral decubitus position [27]. Pelvic vein thrombosis may be suggested when the visualized vein is compressible but there is absence of normal changes in flow during respiration or with the Valsalva maneuver. However, the sensitivity and specificity of Doppler ultrasonography to confirm or exclude iliac vein thrombosis is unknown and has not been rigorously assessed.

If Doppler ultrasonography supports the suspicion for iliac vein thrombosis, treatment is initiated. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)".)

If Doppler ultrasonography does not support DVT, MR venography may be performed. (See 'Alternative: Magnetic resonance venography' below.)

Alternative: Magnetic resonance venography — MR venography is a modality that can detect both proximal and pelvic vein DVT with a sensitivity that approaches 100 percent in the nonpregnant population [28]. A filling defect on MR venography should prompt therapy. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'Alternative imaging' and "Venous thromboembolism in pregnancy and postpartum: Treatment".)

Data regarding MR venography are limited in pregnancy. However, small case series of pregnant patients suggest that this modality is useful for the diagnosis of pelvic and femoral vein thrombosis in situations where other noninvasive examinations are equivocal [29,30]. In a study comparing CUS with MR venography and including 27 females with proximal DVT, 3 cases of DVT in the pelvic veins were missed on ultrasound but detected by MR venography [30]. MR venography was superior at determining proximal propagation into the pelvic veins and inferior vena cava.

In pregnant patients with suspected DVT, MR venography is a safe test and can be performed without contrast [30]. (See 'Radiation and contrast exposure' below.)

Other — Ascending contrast venography is rarely performed in pregnancy due to concerns regarding exposure of the fetus to ionizing radiation and contrast, technical difficulties of femoral vein cannulation, and decreased sensitivity for isolated iliofemoral thrombosis due to abdominal-pelvic shielding to protect the fetus [6,31,32]. Studies that measure the accuracy, sensitivity, and specificity of its use in pregnancy and the postpartum period are lacking. Additionally, CUS approaches ascending contrast venography in diagnostic sensitivity and specificity without these risks, rendering contrast venography less useful than in the past for the diagnosis of DVT [6,31,32].

If performed, a filling defect on ascending contrast venography should prompt therapy. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'Alternative imaging' and "Venous thromboembolism in pregnancy and postpartum: Treatment".)

Concerns regarding the risks associated with contrast are discussed separately. (See 'Radiation and contrast exposure' below and "Pulmonary embolism in pregnancy: Clinical presentation and diagnosis", section on 'Radiation and contrast risk'.)

False negative suspected or inconclusive study — If a false negative study is suspected or the CUS is inconclusive, options include repeating the CUS or performing an alternative imaging study such as MR venography. (See 'Traditional approach: Compression ultrasonography' above and 'Alternative: Magnetic resonance venography' above.)

DIAGNOSIS — The diagnosis of DVT in pregnancy and postpartum is made by demonstrating a lack of compressibility of the proximal or calf veins on compression ultrasonography (proximal or calf vein thrombosis, respectively) or poor flow on Doppler imaging of the femoral-iliac vein (iliac vein thrombosis).

The diagnosis can also be made by the demonstration of a filling defect on magnetic resonance venography or ascending contrast venography. (See 'Alternative: Magnetic resonance venography' above and 'Other' above.)

Elevated D-dimer levels and clinical examination cannot be used alone to diagnose DVT in this population. (See 'Low or moderate clinical suspicion: D-dimer' above.)

RADIATION AND CONTRAST EXPOSURE — There is no radiation exposure associated with ultrasound or magnetic resonance imaging. However, there are risks to the fetus and mother associated with radiation exposure for contrast venography and with iodinated and gadolinium contrast for venographic studies. The risks of radiation exposure and contrast administration during pregnancy are discussed in detail separately. (See "Pulmonary embolism in pregnancy: Clinical presentation and diagnosis", section on 'Radiation and contrast risk' and "Diagnostic imaging in pregnant and lactating patients", section on 'Magnetic resonance imaging'.)

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".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Deep vein thrombosis (blood clot in the leg) (The Basics)")

●Beyond the Basics topics (see "Patient education: Deep vein thrombosis (DVT) (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Clinical presentation – The clinical presentation of lower extremity deep vein thrombosis (DVT) during pregnancy is similar to that in nonpregnant females (eg, diffuse pain and swelling of the lower extremity that may or may not be associated with erythema, warmth, and tenderness). However, pregnant individuals have a higher rate of left-sided DVT and pelvic (ie, iliac) vein thrombosis. Symptoms of DVT may also overlap with features of normal pregnancy. (See 'Clinical presentation' above and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

●Initial diagnostic evaluation – A high index of clinical suspicion is necessary for the diagnosis of DVT in pregnancy. We use gestalt suspicion rather than pretest probability scores since the latter are unreliable in this population. (See 'Assessing pretest probability' above.)

We describe two approaches to diagnostic evaluation; choosing between them depends on clinician preference, resource availability, clinical suspicion, and patient preference.

•The traditional approach – In the traditional approach, all pregnant patients suspected of having a DVT undergo initial evaluation with compression ultrasonography (CUS) (algorithm 1). Whole-leg rather than proximal vein CUS should be used since it can detect calf vein as well as proximal vein DVT.

CUS is a sensitive and specific test for the diagnosis of DVT, is noninvasive, and is not associated with radiation toxicity. However, immediate access is not universally available, expertise is needed to preform and interpret the test, and cases of pelvic vein thrombosis may be missed. (See 'Traditional approach: Compression ultrasonography' above.)

•Alternative approach – As an alternative approach we use clinical suspicion to dictate testing (algorithm 2) (see 'Alternative approach based on clinical suspicion' above):

Low or moderate suspicion – In patients with a low or moderate clinical suspicion for DVT, we measure D-dimer. In such patients, D-dimer has a high negative predictive value. However, D-dimer becomes less useful with gestational age and there is no agreed-upon pregnancy-adjusted reference range. In the absence of a validated single cutoff, we use the traditional cutoff value of 500 ng/mL. (See 'Low or moderate clinical suspicion: D-dimer' above.)

-A negative D-dimer in this population may be used to exclude DVT and avoid imaging with CUS. Patients should be observed clinically and asked to return immediately for any progressive signs or symptoms of DVT.

-A positive D-dimer is not helpful and CUS should be performed (preferably whole-leg CUS).

High suspicion – For patients with a high clinical suspicion for DVT during pregnancy, proximal vein CUS should be performed without obtaining a D-dimer level. (See 'High clinical suspicion: Compression ultrasound' above.)

●Subsequent testing – The need for additional testing is dependent on proximal vein CUS results and clinical suspicion for proximal vein, pelvic vein, or calf vein DVT. (See 'Need for subsequent testing' above.)

•If CUS is negative and congruent with a low or moderate clinical suspicion, we do not typically perform additional testing, although the threshold to order additional testing (eg, serial CUS) should be low for those in whom clinical suspicion is in the moderate range or those in whom only proximal vein rather than whole-leg CUS was performed. Patients are followed clinically for any signs of DVT as the pregnancy progresses. (See 'Negative CUS congruent with low or moderate clinical suspicion' above.)

•If proximal CUS is negative but clinical suspicion for DVT remains, we perform serial proximal vein CUS on day 3 and 7 without empiric anticoagulation; other options include measuring D-dimer level or whole-leg CUS if neither has been performed yet. Notably, the suspicion for calf vein DVT should be very low if initial whole-leg CUS was negative. If iliac vein DVT is suspected, we perform Doppler ultrasound directed at the iliac vein; another option is to perform magnetic resonance (MR) venography without contrast. If a false negative CUS is suspected or CUS is inconclusive, repeat CUS or alternative imaging are options. (See 'Negative CUS incongruent with clinical suspicion' above.)

●Diagnosis – The diagnosis of DVT during pregnancy and postpartum is made by demonstrating a lack of compressibility of the proximal or calf veins on CUS (proximal or calf vein thrombosis) or poor flow on Doppler imaging of the femoral-iliac vein (iliac vein thrombosis). It can also be made by the demonstration of a filling defect on MR venography. (See 'Diagnosis' above.)

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