Laboratory Evaluation for DVT
D-dimer is often used in non-pregnant patients due to its high negative predictive value. D-dimer increases progressively throughout gestation, [39] adding to the difficulty in selecting an appropriate cut off value for reasonable specificity in pregnancy. The high negative predictive value of d-dimer for DVT in pregnancy has also been demonstrated prospectively [40, 41, 42] ; Note, however, data to support its use in the setting of suspected PE is sparse, and D-dimer may have lower sensitivity in pregnancy.
A study by Chan et al suggests that DVT may be safely excluded if the d-dimer is negative and the compression duplex ultrasonography (CUS) is normal. One hundred forty nine consecutive pregnant women were evaluated for possible DVT. Twelve were diagnosed with DVT and 1 with PE. D-dimer testing (SimpliRED assay) was positive for all 13 patients (100% sensitivity), and the specificity was 60% (identifying correctly as negative for VTE 81 of 135 patients). This study demonstrated a 100% negative predictive value in pregnancy. [41] Use of a sensitive d-dimer test coupled with compression duplex ultrasonography may be a useful algorithm for evaluation of DVT in pregnancy, although more research is needed in this area.
One suggested algorithm integrating d-dimer testing is listed below [20] :
Diagnostic algorithm for suspected Deep-Vein Thrombosis and Pulmonary Embolism during pregnancy.
Laboratory Evaluation for PE
As discussed, d-dimer can be used outside of pregnancy for its negative predictive value in settings in which PE is suspected but unlikely [41] ; however, it is less specific in pregnancy. [43] D-dimer has not been prospectively validated in the setting of suspected PE in pregnancy as it has been for DVT. Furthermore, a small retrospective study by Damodaram, et al reported poor sensitivity of only 73% for PE. [44]
Arterial blood gas has been used to evaluate the alveolar-arterial oxygen gradient. An identified increase in Alveolar-arterial (A-a) gradient may be due to a mismatch in ventilation/perfusion as seen with pulmonary embolism. The A-a oxygen gradient is not sensitive for PE in pregnancy, limiting its use. In a study of A-a gradient in 17 pregnant women with PE, [28] 58% had documented normal A-a oxygen gradients. [45] See the A-a Gradient calculator.
Other laboratory testing (eg, cardiac enzymes, arterial blood gas, brain natriuretic peptide) is not typically helpful other than to evaluate for a possible alternative diagnosis to PE.
Imaging for DVT
The current initial test of choice in the evaluation of VTE is compression ultrasound (CUS) of the lower extremity veins. CUS has been shown to be more than 95% sensitive and specific for proximal lower extremity DVT. [4]
As mentioned above, CUS is not as accurate for diagnosis of pelvic DVT as for extremity DVT. [5] In pregnancy, CUS should be performed with the patient in the left lateral decubitus position and with Doppler analysis of flow variation during respiration to maximize the studies ability to diagnose pelvic DVT. [6]
If pelvic DVT is not suspected and the results of CUS with Doppler analysis are negative, the patient may return to routine observation. However, if the study is equivocal, if Doppler testing is abnormal, or if one’s suspicion of pelvic DVT is high, further evaluation with MRI is recommended. [7, 8, 9] MRI has been shown to have 97% sensitivity and 95% specificity for pelvic DVT in nonpregnant patients. [10] The American College of Obstetricians and Gynecologist Practice No 132 states that presumptive anticoagulation therapy may be appropriate in certain circumstances when one suspects pelvic DVT. [7] If index of suspicion for DVT is low and the results of CUS are negative, one may defer anticoagulation therapy, and the patient may be monitored. Examination of d-dimer levels may negate the need for further imaging or anti-coagulation in the setting of suspected DVT due to d-dimer’s high negative predictive value.
Imaging for PE
Imaging for either DVT and/or PE are the best methods to screen and evaluate for these issues. Note that the evaluation for suspected PE in pregnancy is similar to the nonpregnant individual. Although both spiral CT pulmonary angiogram (CTPA) and ventilation-perfusion scanning (V/Q) expose the fetus (or embryo) and mother to ionizing radiation, these potential risks must be compared to the up to 30% mortality in patients with PE left undiagnosed and untreated.
If at initial presentation a patient has concomitant symptoms or signs consistent with DVT and PE, compression ultrasonography may be considered first. If diagnostic for DVT, anticoagulation therapy is recommended, which is appropriate for both DVT and PE, avoiding further unnecessary testing for PE. A negative compression ultrasonography of lower extremity veins however does not exclude PE. If clinical suspicion still exists, further chest imaging is necessary.
A chest radiograph is recommended prior to the evaluation for PE to define other etiologies that may explain the symptoms (eg, pneumonia, atelectasis, pulmonary edema) and define the appropriate next imaging test.
Two alternative radiologic modalities exist for diagnosis of PE are spiral CT pulmonary angiography (CT-PA) and ventilation-perfusion (V/Q) scan. In the pregnant patient with no known pulmonary disease and a normal chest radiograph, ventilation-perfusion scan is the recommended study to evaluate for PE. If the patient has an abnormal chest radiograph or known pulmonary disease, spiral CT pulmonary angiography is recommended. [11]
The CT-PA uses IV contrast followed by CT scan. Filling defects may be seen on CT that are diagnostic of PE. The CT-PA is less accurate in detection of small or emboli at the peripheries of the lung. In the nonpregnant population, CTPA is preferred.
V/Q scanning is a 2-phase test. In the ventilation phase, a medical radionuclide gas is inhaled by the patient to demonstrate where air is entering the lungs. Next, the perfusion phase uses intravenous radioactive contrast to determine where blood flow is passing through the lungs. Images of both phases of the study are compared.
Areas where gas enters the lungs but blood does not may indicate embolus. The study is reported as normal, low, intermediate, or high probability for PE. These results then must be considered with pretest clinical probability of PE. Only low pretest probability combined with negative or low probability scan and high pretest probability combined with high probability scan results are diagnostic. Some patients may require CTPA after nondiagnostic V/Q scanning for definitive diagnosis, or vice versa.
V/Q scanning maybe less diagnostic in the setting of pre-existing pulmonary disease in the general population; however, in a young pregnant population these disease states are less likely. Several studies have demonstrated V/Q scanning to be either comparable or superior to CTPA for diagnosis of PE in pregnancy when chest radiographs are normal. [46, 47] The clinician’s choice of imaging test may depend on clinician preference, availability, and experience of the radiologist at the institution.
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Estimated gestational age at time of diagnosis of antepartum deep venous thrombosis (n=94).
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May-Thurner syndrome
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Factors affecting thrombosis in Pregnancy
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Diagnostic algorithm for suspected Deep-Vein Thrombosis and Pulmonary Embolism during pregnancy.
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Suspected pulmonary embolism
Tables
Risk Factor |
Recommendations |
Women with a single episode of VTE associated with a transient risk factor that is no longer present |
Clinical surveillance and anticoagulant prophylaxis postpartum* |
Women with a single episode of VTE and thrombophilia (confirmed laboratory abnormality) and a strong family history of thrombosis who are not receiving long-term anticoagulants |
Prophylactic or intermediate-dose LMWH or unfractionated heparin (UFH), plus postpartum anticoagulation for at least 6 wk (for a total minimum duration of therapy of 6 mo) |
Women with antithrombin deficiency and no previous VTE |
Antepartum and postpartum prophylaxis |
Women with thrombophilia (other than antithrombin deficiency) and no previous VTE |
Clinical surveillance or prophylactic LMWH or UFH and anticoagulant prophylaxis postpartum* |
Women with multiple (≥ 2) episodes of VTE who are not receiving long-term anticoagulants |
Prophylactic, intermediate-dose or adjusted-dose UFH or adjusted-dose LMWH followed by long-term anticoagulation postpartum |
Women with multiple (≥ 2) episodes of VTE who are receiving long-term anticoagulants |
Adjusted-dose UFH or LMWH followed by resumption of long-term anticoagulation postpartum |
All women with previous DVT, antenatal and postpartum |
Use of graduated elastic compression stockings |
Women with recurrent pregnancy loss (≥ 3 miscarriages) and women with severe or recurrent preeclampsia, placental abruption, or otherwise unexplained intrauterine growth retardation |
Screen for thrombophilia and antiphospholipid antibodies |
Women with antiphospholipid antibody syndrome and a history of multiple (≥ 2) early pregnancy losses or ≥ 1 late pregnancy losses, preeclampsia, intrauterine growth retardation (IUGR), or abruption |
Antepartum aspirin plus prophylactic or intermediate-dose UFH or LMWH |
Women with APLAs and a history of VTE who are usually receiving long-term oral anticoagulation therapy |
Adjusted-dose LMWH or UFH therapy plus low-dose aspirin and resumption of long-term oral anticoagulation therapy postpartum |
* If the previous risk factor is pregnancy or estrogen-related or additional risk factors (such as obesity) are present, antenatal anticoagulant prophylaxis is recommended. |
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