Tintinalli page 441 Different in diagnosis & treatment Limit testing and reduce exposure by shielding and appropriate choice of tests Warfarin crosses the placenta – Heparin & Clexane do not cross – can be started in high suspicion before results available VQ scanning is assoc with higher risk of childhood Ca but carries lower risk of maternal breast Ca 1 case in 280000 vs &lt;1 case in 1 million for unexposed children Lifetime risk 13% higher with CTPA vs VQ Should consider the trimester of the pregnancy First trimester – 750ng/ml Second trimester – 1000ng/ml Third trimester – 1250 ng/ml
This hypercoagulability is multifactorial and probably is caused by a combination of venous stasis and altered levels of circulating clotting factors during pregnancy and the puerperium. Protein S levels decline with increasing gestation, though Protein C activity unaffected. Circulating levels of multiple clotting factors (I, II, VII, VIII, IX, & X) are elevated in pregnancy & the puerperium – mainly factor VII & fibrinogen Venous stasis may occur at the end of the first trimester, due to enhanced compliance of the vessel walls by a hormonal effect.
Compressive ultrasound is noninvasive and has been found to have a sensitivity of 97% and a specificity of 94% for the diagnosis of symptomatic, proximal DVT in the general population. The test has no radiation exposure and no known risks to mother or fetus. - Clinical presentation and routine laboratory information, such as chest pain, tachypnea, dyspnea, hypoxia, arterial blood gasses, electrocardiography, and chest radiography are often the first indications that PE is present. - It is reasonable to start with bilateral lower-extremity ultrasound, and if thistest is positive, to treat for VTE. In the face of negative ultrasonography, however, further testing is warranted for evaluation of suspected PE.
Dyspnoea occurs in up to 70% of all normal pregnancies
From a data base of 160 pregnant women worked up for PE, vitals signs in the 8 confirmed with PE did not distinguish them from those without. If PERC negative then measure D Dimer, adjusting for nomral elevtions in pregnency
4 DVTs occur for every 1 PE in Pregnancy
- Encouraging fluid intake and having the patient void frequently for 4 to 6 hours after the test can minimize radiation exposure. Technetium 99m is excreted renally and collects in the bladder, increasing radiation exposure to the fetus by the proximity of the radioactive material. Technetium 99m also is excreted in breast milk, so women who undergo this test after delivery should substitute formulafor breast milk for 2 days.
- Helical CT scanning has provided an alternative diagnostic tool for the visualization of PEs. CT scanners continue to offer improved technology, scanning times, visualization, and sensitivity.***although this has not been demonstrated in a study of over 300 neonates.
MRI and magnetic resonance angiography with gadolinium enhancement has been studied, and some studies have shown sensitivities as high as 100% and specificities of 95%, although small PEswere not detected in this study.- Gadolinium has not been proved to be safe in pregnancy, and its use should be avoided during pregnancy, if possible.
Intravenous heparin is the initial treatment of choice for PE and is the best therapy immediately before delivery because of its short half-life. Subcutaneous unfractionated heparin and low-molecular-weight heparins (LMWH) have risks and benefits but can be used during pregnancy.Warfarin is assoc with higher rate fetal complications, incl miscarriage, stillbirth, congential malformations. Wafarin / UFH / Clexane are safe in lactation A Cochrane review of 22 studies had over 8000 patients of whom 75% had DVT and 25% PE without evidence of DVT; compared with unfractionated heparin, LMWH treatment was associated with lower rates of VTE recurrence or extension (3.6% versus 5.4%; OR 0.68, 95% CI 0.55–0.84), lower mortality (4.5% versus 6.0%; OR 0.76, 95% CI 0.63–0.92) and less major bleeding during the initial treatment period (1.2% versus 2.0%; OR 0.57, 95% CI 0.39–0.83).80
IVC filters - indications are the same asfor the nonpregnant population. Patients with such indications include:(1) patients with acute VTE and contraindications to anticoagulation,(2) patients who have an episode of acute VTE while appropriately anticoagulated, and (3) patients who are critically ill and at risk for recurrent embolism in whomrecurrent embolism is likely to be fatal
Sensitivity was based on number of patients who had conclusive interpretations of CTA or CTA-CTV. Sensitivity would be lower if patients with inconclusive interpretations (owing to poor image quality) were included. Data reported with four-slice CT. Advanced scanners with 8-slice or 16-slice scanners were not studied. Reference standard used noninvasive diagnostic tests The false negative rate (17%) was higher than anticipated It&apos;s unclear if the accuracy will be affected if the clinical suspicion comes from a trainee rather than a seasoned clinician The double reading by radiologists is unrealistic
Investigation of suspected pulmonary embolism in pregnancy
PE in Pregnancy
Dr Chantelle Badawy
ED Registrar – CME - SCGH
The risk of PE in the non-pregnant female risk is 1 in 100,000, this
increases to 1 in 10,000 in pregnant age-matched females.
PE occurs in 1 of 1600 pregnancies
PE during pregnancy may be fatal in almost 15% of patients, and
in 66% of these, death will occur within 30 minutes of the embolic
PE is a leading cause of Maternal mortality in the developed
In Australia, the leading causes of direct maternal deaths
(when combined = ¾ all maternal deaths)
amniotic fluid embolism (9),
obstetric haemorrhage (7)
Sepsis and cardiac conditions were the leading causes of
maternal death for Indigenous Australians.
Why is this so important?
VTE is a significant cause of morbidity and
mortality during pregnancy. The clinical
evaluation alone cannot confirm or refute a
diagnosis of VTE in the non-pregnant population,
and diagnosing VTE during pregnancy is more
Ultimately - nobody “WANTS”
to perform a peri-mortem cesarean
Why is it difficult to evaluate?
Difficulty and confusion arises in the work up of PE in the
pregnant patient due to 3 things:
1.The normal physiological changes in pregnancy;
dyspnoea, tachycardia and leg swelling are also
common PE symptoms
2.The pre-test probability score, (Wells & PERC), cannot be
used in a pregnant patient as they were excluded from
the analysis group for criteria validation.
3.The d-dimer will rise in the second trimester and remain
elevated for 4-6 weeks post-partum.
The diagnosis of VTE during pregnancy often is impaired
by a reluctance to expose a pregnant patient and her
fetus to radiation.
Multiple Risk factors at play…
1)Pregnancy itself is a risk factor
2)Prev VTE in pt on hormonal contraception
3)Prev VTE during pregnancy (risk 12%)
4)Rheumatic heart disease and pts with heart prosthesis
6)Age > 35yrs
7)Obesity BMI > 30
10)Bed rest & physical immobility
12)Shock & dehydration
Why is it difficult to evaluate?
The pregnant patient fulfills all of Virchow’s
Emboli cause respiratory compromise due
to lack of perfusion of ventilated lung and
heamodynamic compromise due to
increased pulmonary arterial resistance
Diagnosis of PE & DVT
Diagnosis of pulmonary embolism
Routine lab evaluation
Diagnosis – Clinical Sympotms
The classic symptoms of VTE are less specific during
pregnancy than during the non-pregnant state.
Sweating (18%) Dyspnea (62%)
Pleuritic chest pain (55%) Cough (24%)
Tachycardia & palpitations Tachypnoea
Leg swelling & pain Haemoptysis
There are no clinical S&S that are specific for PE, esp in
pregnancy. Consider that dyspnoea occurs in up to 70% of
all normal pregnancies
Clinical suspicion must remain high, and the appropriate
diagnostic workup should ensue.
Diagnosis – Pre-test Probability
There is no evidence for the use of (WELLS) pretest probability
assessment in the management of acute VTE in pregnancy.
Pregnant patients were excluded form the validation trials
and therefore no supporting data
Modified Wells which takes into account leg circumference
and trimester has a high sensitivity & specificity though there
is not enough data to put this to use at this point.
Unfortunately, the PERC rule has not been validated in
Kline is in the process of validating a modified PERC for
pregnant patients, to be used with HR >105 & applied to
low risk patients to risk – however this lacks evidence at this
Diagnosis - ABG
Limited diagnostic value (for pregnant & non-pregnant)
Resp alkalosis is common in both pregnancy and PE.
In one study, ABG analysis showed that only 10% had
arterial PO2 levels less than 60 mmHg and 2.9% had oxygen
saturation levels less than 90%.
The presence of hypoxaemia and normal CXR should raise
the suspicion for PE in pregnancy
Diagnosis - ECG
The ECG changes associated with acute PE may be seen in any
condition that causes acute pulmonary hypertension, including
hypoxia causing pulmonary hypoxic vasoconstriction.
One study found that the ECG was abnormal in 41% of women
with acute PE; the most common abnormalities were
T wave inversion (21%),
S1Q3T3 pattern (15%)
Right bundle branch block (18% during pregnancy and 4.2% in
Given the increasing incidence of IHD in pregnancy, the ECG
may also be helpful in identifying alternative diagnoses
T-wave inversions in the right precordial leads (V1-3) as well as lead III
Extreme right axis deviation (+180 degrees)
S1 Q3 T3
T-wave inversions in V1-4 and lead III
Clockwise rotation with persistent S wave in V6
Diagnosis - CXR
Exclude or diagnose other pathology
Eg – pneumonia, pneumothorax or lobar collapse.
CXR is normal in >50%pt with proven PE.
Abnormal features caused by PE include atelectasis, effusion,
focal opacities, regional oligaemia or pulmonary oedema.
Normal CXR prior to V/Q scanning improves the likelihood of a
definitive V/Q result.
If the CXR is abnormal with a clinical suspicion of PE, CTPA should
Diagnosis – D Dimer
Currently, the general consensus is still that D-dimer is not an
adequate enough test to rule-out a pulmonary embolism in a
60% of healthy patients in normal pregnancy will have a raised D-
A ‘positive’ D-dimer test in pregnancy is not necessarily consistent
with VTE. The role of D-dimer testing in the investigation of acute
VTE in pregnancy remains controversial.
Kline proposes that an altered “normal value” in pregnancy is
First trimester - 50% above upper limit
Second trimester – Double the upper limit
Third Trimester - 2.5 times the upper limit
Diagnosis – Compression Ultrasound
DVT are the source of more than 95% of PE and the prevalence of
PE correlates with predisposition to leg thrombosis - hence if you
find a leg DVT on US you can stop investigating (also given the DVT
& PE treatment are the same)
This strategy has been evaluated in a prospective cohort study of
221 pregnant women who presented with suspected DVT.’
Sensitivity of serial doppler - 94.1% (95% CI 69.2–99.7%)
Diagnosis of deep vein thrombosis
Ultrasound – Sensitivity 97% & Specificity 94%
No radiation exposure
Diagnosis - VQ Scan
The amount of radiation exposure varies
based on the isotope used, but VQ
scanning can be performed safely
It is possible to exclude the initial
Ventilatory (V) phase of the scan (if
normal CXR) and therefore reduce the
Many authorities continue to
recommend V/Q scanning as first-
line due to in its high negative
predictive value & its substantially
lower radiation dose to pregnant
Diagnosis - CTPA
CTPA has potential advantages over V/Q imaging
CTPA is more readily available,
Delivers a low radiation dose to the fetus
Can identify other pathology
There is a theoretical risk of hypothyroidism for neonates who
have been exposed in utero contrast**
Suggest IDC & IV Fluid to “flush” the contrast rapidly and avoid
excessive exposure time to feotus - contrast crosses placenta &
collects in amniotic fluid.
The radiation exposure is comparable
to that of VQ scan and is within the
amount considered to be safe in
The use of MRI to diagnose
acute PE has been explored
but is not recommended for
routine diagnosis of PE.
Gadolinium should not be
used in pregnancy where
Test Whole body
Risk to mother
Risk to Feotus
CXR 0.07 0.01
CTPA 1.6-8.3 Lung
3.3 – 130
above BG risk
0.3 – 7.4
Bg rad / year 2.5 Dose 100mGy
= <1% risk
Max allow rad
(Avge = 20)
wt factor/ or
*13.6% of 0.1%
risk in 25yo =
risk (very little)
How to understand the Radiation exposure
to fetus (Kline)
Threshold for dangerous radiation 0.1Gy = $100
(greater than this is believed to be excessive & possibly cause congenital
Fetal absorbed CXR is 0.1 Cent
CTPA 25-50 Cents VS VQ – 50-75 Cents
BG radiation to fetus over 9 months $5
Radiation to increase lifetime Ca risk before age 20 by 1 in 10 000 is
Argued that there is no reliable way to measure these doses and
effects in utero.
Exposure to Mum – age you about 3 years (ie equivalent to 3yrs
normal background radiation)
UFH (Pregnancy Cat C) & LMWH (Pregnancy Cat C) can be
used in pregnancy
IV Heparin immediately before delivery is ideal given is short half
life. Heparin does not cross the placenta & does not carry risks for
teratogenesis and fetal hemorrhage, although bleeding at the
uteroplacental junction is possible.
- Warfarin (Pregnancy Cat D) crosses the placenta, is
teratogenic and are contraindicated during some stages of
In the initial management of DVT, the leg should be elevated
and a graduated elastic compression stocking applied to
reduce oedema. Mobilization with graduated elastic
compression stockings should be encouraged.
Treatment – unstable
Massive PE may present with shock, refractory hypoxaemia
and/or right ventricular dysfunction on echocardiogram and is
a medical emergency.
Collapsed, shocked women who are pregnant or in the puerperium
should be assessed by a multidisciplinary resuscitation team of
Supportive care and intravenous anticoagulation should be instituted
Subsequent treatment options are controversial and include IVC filter
placement, thrombolytics, and embolectomy.
Sudden death, cor pulmonale, or cardiovascular collapse occurs
when 60% or more of the pulmonary circulation is obstucted with
PIOPED II Study
Study question – Clinically suspected acute PE, what is the
diagnostic accuracy of CTPA?
PIOPED II (2006) is the largest study to date which compared CTPA
against a composite reference standard and demonstrated an 83%
sensitivity and 96% specificity in detecting an acute PE.
PIOPED II suggested that the predictive value of CTPA is highly
concordant with the pretest clinical probability of PE using Well's
Design - Prospective, multicenter(8) , comparison study (7,284
screened, 3,262 eligible, 1,090 enrolled)over 2001-2003
N=824 completed evaluation for diagnosis of PE by both:
Composite reference standard, and
***Interestingly, “Possible Pregnancy” was an exclusion
criteria for this study
PIOPED II Study
Made the following recommendations
1.D Dimer with clincal assessment should be
2.If D-Dimer is positive, venous Ultrasound is
recommended before using radiaiton imaging
3.69% of PIOPED II investigators recommend
Pulmonary VQ scan and 31% recommend CTPA.
Stein PD, et al. "Multidetector Computed Tomography for Acute
Pulmonary Embolism". The New England Journal of Medicine.
Kline : Systematic review and meta-analysis
of PE in Prengnacy (May 2014)
Studies in all languages from multiple databases in Feb 2014, ED pts with
Outcome of VTE+ ( DVT or DVT&PE)
Papers were assessed for selection and publication bias, and heterogeneity
Seventeen full-length studies of 25,339 patients were analysed.
The frequency of VTE+ rate among the 506 pregnant patients was 4.1% (2.6-
6.0) compared with 12.4% (9.0-16.3) among non-pregnant patients.
The pooled RR of pregnancy for VTE+ diagnosis was 0.60 (0.41-0.87).
Patients in the third trimester had an RR of 0.85 (0.40, 1.77) and patients of
childbearing age(≤45 years) had an RR of 0.56 (0.34 to 0.93).
In the ED setting, physicians test for PE in pregnant patients at a low
threshold, resulting in a low rate of VTE diagnosis (4.1%, 95% CI: 2.6-6.0)
Relative risk of VTE that is lower than non-pregnant women of childbearing
age who are tested for PE in the ED setting.
Higher risk of PE in pregnancy – must have clinical suspicion
Wells & Perc have not been proven in pregnancy
D Dimer is limited value unless alter cut off values
Always consider Lower limb ultrasound first – if POS then
treat. If NEG keep looking
If no limb symptoms or USS Neg perform CXR
VQ Scan (esp Perfusion phase only) presents less radiation
CTPA is useful if CXR abnormal
When in doubt, treat until confirm/refute diagnosis
Engage multiple team members in decisions, keep the
patient well informed and discuss radiation risks openly