Thanks to everyone who contributed to the discussions about the investigation of Mrs Marks’ symptoms, which suggested she may have a pulmonary embolus during pregnancy. There were some great questions raised and some useful resources highlighted by UCLMS students which you can see in the storify. [View the story “quclms case 2: ?PE in pregnancy” on Storify]
Venous thromboembolism (including deep vein thrombosis, pulmonary embolus and cerebral vein thrombosis), remains a leading cause of maternal mortality and morbidity worldwide so it is important to have an understanding of the principles of investigation and management.
This week’s question setter and expert was Dr Scott Rice, Radiologist at UCLH and Honorary Clinical Lecturer at UCL Medical School
The information provided at the start of the week was::
Mrs Juliette Marks is a 32 year old woman who is 35 + 4 weeks pregnant. She has felt increasingly short of breath for the last 3 days and has right sided chest pain that is worse on taking a breath in. She has no cough and has not had haemoptysis.
This is her first child. She has had an uncomplicated pregnancy, all antenatal screening has been unremarkable and she is due for delivery in the midwife-led birthing unit. She has no significant past medical history and there is no significant family history. She lives with her husband and works as a secondary school teacher. She is a non-smoker, has no allergies and is not taking any medication.
Her initial observations are:
- Temperature: 37.2, HR 129bpm, RR 22/min, GCS 15, BP 138/90mmHg, BM 7.1mmol/L, Sats 90% on air
- A: airway clear
- B: tachypneoic, air entry bilaterally, no crepitations, wheeze or added sounds
- C: pulse rate elevated but of normal volume and character, warm peripherally, heart sounds normal, JVP not elevated. Capillary refill 2 seconds. Calves soft and non-tender with bilateral non-pitting ankle oedema.
- D: orientated to time, place and person. GCS E4 V5 M6. Pupils equal and reactive to light
- E: unremarkable abdominal examination, with gravid uterus and linea nigra
The question prompting discussion on Twitter was: What are the most appropriate investigations for suspected PE in pregnancy?
Venous thromboembolism (including deep vein thrombosis, pulmonary embolus and cerebral vein thrombosis), remains a leading cause of maternal mortality and morbidity worldwide, although the United Kingdom Centre for Maternal and Child Enquiries reported a significant fall in maternal death due to VTE during 2006-2008. Physiological changes during pregnancy alter the balance in the haemostatic system in favor of thrombosis. The increased risk of VTE begins in early pregnancy and lasts throughout the puerperium. Pregnancy increases the risk of VTE 5- to 10-fold compared with the non-pregnant state, with VTE occurring in around 1 per 1,000 deliveries.
Investigating venous thromboembolism, including PE, in pregnancy is challenging.
- Pregnancy and the postpartum period lead to changes in all three components of Virchow’s triad: venous stasis, endothelial injury and a hypercoagulable state. Stasis is due to compression of large veins and the Inferior Vena Cava by the gravid uterus, but also due to pregnancy-associated venous pooling. Endothelial injury occurs during delivery, particularly in forceps or surgical delivery. Pregnancy is a hypercoagulable state with decreases in protein S, progressive resistance to protein C and an increase in factors I, II, VII and VIII.
- Usual risk prediction scores (such as the Well’s score) are unreliable in pregnancy. Therefore a thorough and accurate clinical assessment must be made, helping to guide the use of the most appropriate investigations.
- D-dimer is often raised in pregnancy and, if positive, is unhelpful in the risk stratification of VTE so many places advice against it’s use at all in pregnancy
- VQ scan and CTPA are both appropriate investigations for PE in pregnancy. The choice depends on local availability and a balance of risk of radiation with the risk of a missed diagnosis.
- Wells Score for PE
- Negative predictive value – It’s important to consider the reliability of any test in the population in which you are using it (example of a test with poor positive predictive value but good negative predictive value is D-dimer)
- NICE guidelines on VTE diagnosis
- Advice from the Royal College of Radiologists “Radiation and the early fetus”
- Protection of pregnant patients during diagnostic medical procedures to ionising radiation (Health Protection Agency and RCR) – includes estimated fetal radiation dose and risk of childhood cancer.
- RCR guidelines
- RCOG guidelines
Dr Scott Rice, Radiologist at UCLH and Honorary Clinical Lecturer at UCL Medical School says:
Pulmonary embolism (PE) a leading cause of maternal death. The rate of PE in pregnancy 5- to 10 times greater than that for non-pregnant women and the increased risk of VTE begins in early pregnancy and lasts throughout the puerperium. The clinical diagnosis of PE is often difficult and can lead to confusion and anxiety for patients and clinical teams alike.
This has been an excellent discussion but highlights the ongoing uncertainty faced in investigating and diagnosing PE.
- Precise PE diagnosis in pregnancy is vital to prevent unnecessary treatment of PE as treatment is associated with side effects for both the mother and fetus. The diagnosis can be complicated in pregnancy as some of the clinical symptoms of PE can be normal/expected symptoms of pregnancy. However, physiological changes during pregnancy alter the balance in the haemostatic system in favour of thrombosis.
- Clinicians should always have a high index of suspicion in view of the potential severity and mortality associated with PE. Symptoms and signs include pleuritic chest pain, dypspnoea, tachypnoea, cough, haemoptysis, tachycardia, raised JVP, focal chest signs and evidence of DVT. A large PE may present with collapse and shock.
- Remember, it is estimated that 70% of patients with a proven PE have proximal deep venous thrombosis and therefore clinical diagnosis must include assessment for venous thromboembolism: Assess for painful, swollen, red, legs. DVT is much more common in the left leg during pregnancy (frequency 9 : 1) due to increased venous stasis.
- Subjective assessment is wrong in about 50% of cases and therefore objective assessment is key to avoiding missed diagnosis or inappropriate treatment. All women with suspected PE should undergo a full clinical assessment, arterial blood gas analysis, ECG and a chest radiograph. There was some debate amongst twitter users about the usefulness of the chest film; this is to guide the next step – those who felt a PE would not be seen on CXR are correct; however it is extremely valuable in excluding other differentials such as heart failure, pneumonia, or pneumothorax. More commonly, where normal, it will enable VQ scanning to be utilised reliably.
- Do not perform a D-Dimer test: The d-dimer is known to increase in pregnancy and starts to rise during the second trimester, returning to baseline levels at 4–6 weeks post partum.
- Accurate imaging is essential, but there are frequently anxieties relating to fetal and maternal breast radiation exposure during diagnostic procedures.
Normal chest radiograph
- A duplex ultrasound of both lower limbs should be perfomed via radiology or vascular laboratory; if positive the woman should be treated appropriately. There is no need for further imaging to confirm PE.
- If the duplex assessment is negative a VQ or CTPA should be performed. This will be discussed below.
Abnormal chest radiograph
- This is often a difficult clinical scenario but the key question is; can the underlying finding on the radiograph explain the symptoms? If there is a significant pneumonia that is more likely to explain the diagnosis, treat the problem. However, if not (and this is more common) proceed as above with a duplex ultrasound of both lower limbs. If this is negative a CTPA is required; an abnormal chest film excludes a VQ scan in this scenario.
VQ or CTPA
- Having decided that PE remains the top differential and there is no evidence of a DVT in either limb, the question turns to what is the most suitable imaging protocol for imaging the pulmonary tree. The general principle of maintaining a dose as low as reasonably achievable to both the mother and foetus is important. In addition to the radiation risk to the foetus, the breast radiation dose must be considered as the female breast in pregnancy is extremely radiosensitive. For all patients the decision to image at this point should be made by a senior clinician in conjunction with a senior radiologist.
- VQ scanning remains the modality of choice for PE where it is readily available. Perfusion-only (Q) scans may be performed in the pregnant population and have been shown to have a high negative predictive value for PE. There is a lower radiation exposure to the maternal breast, but a slightly higher exposure to the foetus. The ventilation component of the VQ scan may be omitted if the perfusion scan is normal to minimise radiation exposure. VQ imaging is well established for imaging PE and PE can be confidently excluded with a normal VQ scan. However, despite this, the diagnosis of PE should not be delayed by the availability of access to nuclear medicine and in units where it is difficult to arrange VQ imaging CTPA should be considered.
- CTPA is a well-validated investigation and the negative predictive value of a normal CTPA is over 99%. However, CTPA may have a lower diagnostic yield in pregnant patients due to the hyperdynamic circulation.
- CTPA is advantageous as the emboli are directly visualized (unlike for VQ scanning) and alternative causes for the patient’s symptoms may be diagnosed. However, the radiation dose received from CT scanning, particularly to the fetus and maternal breast is higher and this needs careful consideration. It is important to recommend neonatal thyroid testing after a CTPA during pregnancy.
All investigations should be discussed with the patient and this should be documented in the patient’s notes. It is not clear what the absolute radiation risks are for fetus or mother; they are certainly small compared to the risk of a missed diagnosis. The discussion should include an explanation surrounding the risks of undiagnosed PE and possible future risks.
Remember, radiologists are here to help: we understand these can be emotive, stressful and difficult clinical situations and are very happy to provide advice and guidance. Involve us early!