DIAGNOSIS AND MANAGEMENT OF ACUTE VENOUS THROMBOEMBOLISM IN PREGNANCY AND THE PUERPERIUM

Section / Heading / Page
1.0 / Background / 2
2.0 / Aims / 2
3.0 / Broad Objectives / 2
4.0 / Massive life-threatening pulmonary embolus in pregnancy or the puerperium
4.1 Initial Assessment
4.2 Preliminary investigations
4.3 Treatment / 3
3
3
3
3
5.0 / Diagnosis of VTE in pregnancy or the puerperium
5.1 What investigations are needed for the diagnosis of an acute DVT?
5.2 What investigations are needed for the diagnosis of an acute pulmonary embolism (PE)? / 4
5
5
6.0 / Treatment of VTE (either PE or DVT) during pregnancy and the puerperium
6.1 low molecular weight heparin (lmwh) / 6
7
7.0 / Follow up of women with acute VTE during pregnancy or the puerperium / 8
8.0 / Monitoring Compliance / 8
9.0 / Evidence Base / 9
10.0 / Provenance / 11

1.0BACKGROUND

Pulmonary embolism (PE) remains the leading direct cause of maternal death in the UK (1.56/100 000 maternities)1and is the second most common cause of maternal death overall (11% of maternal deaths). Maternal mortality can be reduced by aggressive investigation and treatment of those women with clinical suspicion of venous thromboembolism (VTE). A large population-based case–control study from the Netherlands found a 60-fold increase in the risk of VTE in the first 3 months after delivery compared with non-pregnant controls.4Thus, with approximately 700 000 births/year in the UK, the above incidence of VTE would translate into 700–1400 pregnancy-related VTE episodes/year nationally in addition to those related to miscarriage and termination.With about ten fatalities per year from PE, this translates into an overall case fatality for VTE in pregnancy of approximately 1%. However, clinical signs of VTE in pregnancy are of poor predictive value

The UK Obstetric Surveillance System cohort (UKOSS) of fatal and nonfatal antenatal pulmonary embolism (n= 143) had identifiable risk factors and reported the UK incidence of antenatal PE at 13 per 100,000 maternities.2,3The case fatality rate of PE was reported as 3.5%.

2.0 AIMS

To improve and streamline the management of women during pregnancy and the puerperium with actual or suspected venous thromboembolism. To ensure woman receive appropriate objective testing to confirm or exclude the diagnosis. To ensure that senior staff from different professional groups are involved in the care of the acutely unwell pregnant woman

3.0 BROAD RECOMMENDATIONS

  • Women with acute massive pulmonary embolism should be resuscitated by a multidisciplinary team and senior help called immediately
  • All pregnant or recently delivered women with signs and symptoms suggestive of VTE should be referred to hospital for treatment with low molecular weight heparin and objective testing
  • Women who are stable should be admitted and investigated via the Maternity Assessment Centre (MAC). Unwell women may need admission via A & E for initial resuscitation and care
  • During pregnancy, the investigation of first choice should be that associated with the lowest dose of radiation that could be reasonably expected to confirm the diagnosis
  • D-dimer measurements are of no value in diagnosing acute VTE in pregnancy or the puerperium

4.0 MASSIVE LIFE-THREATENING PULMONARY EMBOLUS IN PREGNANCY OR THE PUERPERIUM

Major pulmonary embolus sufficient to cause maternal collapse may present with sudden onset of chest pain, dyspnoea, hypotension and cyanosis with or without haemoptysis. More minor pulmonary embolism may present with less specific features such as fever, syncope, cough or pleuritic chest pain.

In the context of an acute collapse senior help should be called immediately including the midwifery co-ordinator, the most senior Obstetrician available and the Obstetric Anaesthetist (Contact delivery suite for direct contact on 2065372 at SJUH or 3923830 at LGI).

4.1 INITIAL ASSESSMENT

Initial Assessment should always include:

  • checking and securing the airway
  • assess breathing & record respiratory rate
  • if breathing, deliver high flow oxygen (15litres/min) via a non-rebreathe mask. Check oxygen saturations with an aim to achieve saturation levels of over 95% .
  • if not breathing, need ventilating. Commence bag and mask ventilation till anaesthetist arrives
  • Circulation - check pulse and blood pressure

Record all observations on a MOEWs chart or similar

4.2 PRELIMINARY INVESTIGATIONS

  • Serum urea and electrolytes,; full blood count & coagulation screen
  • arterial blood gases
  • ECG
  • chest X-ray

4.3 TREATMENT

If preliminary assessment clearly suggests a pulmonary embolus, treatment should be started with tinzaparin 175 units/kg/day (use current weight) subcutaneously.

If there is doubt over the diagnosis but a PE is suspected, the first dose of tinzaparin should be given as soon as possibleand objective investigations arranged (see section 6)

The management of women with suspected or confirmed PE should be discussed with the Obstetric, Haematology and, in the acute situation, Anaesthetic consultants. There is also a designated Respiratory registrar who can be contacted for advice and /or review via St James’ Switchboard. Where possible women should be admitted to the obstetric ward. An individual management plan should be documented in the woman’s hospital records for all\women requiring treatment for a VTE

The results of thrombolysis for women with significant cardiovascular compromise show an improvement in haemodynamic stability but no increased survival compared to conventional anticoagulation with heparin. However, in extreme circumstances, the option should be discussed between the Emergency Department Consultant, the physician and the Obstetrician. Ideally a CT pulmonary angiogram within 1 hour of presentation should be used to confirm the diagnosis prior to thrombolysis. However, if this is not possible or the woman not stable enough to allow this, a portable echocardiogram could be considered as an alternative.Maternal bleeding complications are not increased compared to outside pregnancy but fetal death has been reported.

If the woman fails to respond to standard resuscitation she may require pulmonary embolectomy – something which should be discussed between Obstetric, Anaesthetic and Cardiothoracic consultants.

In a moribund patient over 20 week’s gestation, a perimortem Caesarean section should be performed to assist resuscitation.

5.0 DIAGNOSIS OF VTE IN PREGNANCY OR THE PUERPERIUM

The following general rules apply to the investigation and diagnosis of both pulmonary embolus (PE) and deep vein thrombosis (DVT) in pregnancy or the puerperium:

  • Any woman with signs and symptoms suggestive of VTE (either PE or DVT)should be referred urgently for diagnostic testing and
  • Treatment with low-molecular-weight heparin (LMWH) should be commenced and continued until the diagnosis is excluded by definitive testing, unless treatment is strongly contraindicated.

In pregnancy, D-dimer testing is not consistent with VTE and definitive testing is required.

  • D-dimer can be elevated because of the physiological changes in the coagulation system
  • D-dimer levels become ‘abnormal’ at term and in the postnatal period in most healthy pregnant women5
  • A low level of D-dimer in pregnancy is likely, to suggest that there is no VTE, however where there is clinical suspicion objective testing should always be used in pregnancy.

5.1 WHAT INVESTIGATIONS ARE NEEDED FOR THE DIAGNOSIS OF AN ACUTE DVT?

More than 90% of pregnancy-associated deep vein thromboses (DVT) occur in the left leg and involve the iliac system more often than in non-pregnant individuals. Thus all left lower limb pain and/or swelling (and left lower back and flank pain) should be treated with extreme suspicion in pregnant women

Women will normally be admitted to the Maternity Assessment Centre and investigations arranged from there.

Compression duplex ultrasound is the primary diagnostic test for a clinical suspicion of DVT. In St James’ Hospital, due to the high volume of scan requests, ultrasound can only be arranged through face-to –face discussion with a completed request card, by a doctor with the duty sonographer in the main ultrasound department located in Lincoln Wing (Ground Floor). In LGI scans can be arranged by faxing a request card to the main ultrasound department (B Floor, Clarendon Wing). See appendix 1 for useful telephone numbers

Outside normal working hours, the on call radiologist should be contacted via switchboard who will arrange the ultrasound.

  • If testing is negative, and there is a low level of clinical suspicion, anticoagulant treatment should be discontinued.6
  • If ultrasound confirms the diagnosis of DVT, anticoagulant treatment should be continued for the rest of the pregnancy and for a period postnatally of either 6 weeks (distal DVT) or 6 months (proximal/iliofemoral DVT)
  • If ultrasound is negative and a high level of clinical suspicion exists, the woman should remain anticoagulated and the ultrasound repeated in 1 week or an alternative diagnostic test employed.
  • When iliac vein thrombosis is suspected (backpain and swelling of the entire limb), magnetic resonance venography or conventional contrast venography may be considered.7

5.2 WHAT INVESTIGATIONS ARE NEEDED FOR THE DIAGNOSIS OF AN ACUTE PULMONARY EMBOLISM (PE)?

Where there is clinical suspicion of pulmonary embolus, a chest X-ray (CXR) should be performed.

Abnormal features caused by PE include atelectasis, pleural effusion, focal opacities, regional oligaemia or pulmonary oedema.8Whilst the X-ray is normal in over 50% of pregnant women with objectively proven PE, CXR may identify other pulmonary disease such as pneumonia, pneumothorax or lobar collapse.9 The radiation dose to the fetus from a chest X-ray performed at any stage of pregnancy is negligible. Any queries regarding the interpretation of chest X-rays can be discussed with the on-call respiratory registrar or a radiologist

Compression duplex Doppler should be performed where CXR is normal.

  • If both tests are negative with persistent clinical suspicion of an acute PE, the current consensus within the Leeds Teaching Hospitals Trust is that in ante-natal women, the next line of investigation is a half dose lung perfusion (Q) scan.Exclusions to this guidance include situations where the woman has a pre-existing respiratory pathology such as asthma or chronic obstructive airways disease (COPD) which can lead to abnormal lung perfusion even in the absence of PE.
  • Choice of investigation should be made in conjunction with a radiologist who should also review the CXR to ensure that it is normal. Radiologists can usually be contacted in the reporting rooms of the nuclear medicine departments during normal working hours (see Appendix 1 for numbers).
  • Woman must have had a normal CXR within 24 hours of performing a lung perfusion (Q) scan.
  • Computerised Tomography Pulmonary Angiography (CTPA) is the investigation of choice in post partum women
  • Computerised Tomography Pulmonary Angiography (CTPA) is also the investigation of choice in women with an abnormal CXR which does not explain their symptoms or in those who have known asthma or COPD.

Women should be involved in the decision to undergo CTPA or lung perfusion scanning, where possible. Informed consent should be obtained before these tests are undertaken.

5.2.1 Counselling Prior To CTPA or Lung Perfusion Scanning

  • Overall CTPA has a slightly higher sensitivity and specificity for the detection of PE but it imparts a higher radiation dose to maternal breasts and in pregnancy has a higher chance of being non diagnostic due to dilution effects caused by physiological changes7
  • Lung scintigraphy has a very high negative predictive value and can be reliably used to exclude PE if it is normal.
  • CTPA may identify other pathology, such as aortic dissection to account for the woman’s symptoms.
  • Women with suspected PE should be advised that whilst both imaging techniques involve a slight risk to both mother and baby but that the risk is far outweighed by the risk of an untreated PE or unnecessary anti-coagulant therapy (see appendix 2 for absolute risks).
  • There have been concerns over the safety of iodinated contrast medium with CTPA, as this can potentially alter fetal or neonatal thyroid function. Current European guidelines indicate that iodinated contrast media may be given to a pregnant woman when radiographic examination is essential10
  • Anticoagulant treatment should be continued until PE is definitively excluded.

6.0 TREATMENT OF VTE (EITHER PE OR DVT) DURING PREGNANCY AND THE PUERPERIUM 11

  • All patients with DVTs should be treated initially with elevation of the affected limb and rest.There is no evidence that early mobilisation increases the risk of PE by "dislodging" thrombus from the deep veins and women should be encouraged to mobilise as soon as pain allows.
  • All patients with a DVT should be considered for Class 2, below-knee graduated compression hosiery. They should have a limb assessment to ensure there is no contraindication to compression (see appendix 3). Referral can then be made to orthotics using form WNU543 which is stocked on the wards and should be completed by the medical staff (this may take up to one week which will allow the initial swelling to reduce). Note that "TED-stockings"are not designed for use in ambulant patients.
  • Adjusted dose low molecular weight heparin (LMWH) e.g. tinzaparin175 units/kg daily for remainder of pregnancy and for at least 6 weeks postpartum.
  • The duration of postpartum therapy will depend on the timing, extent and circumstances of the VTE. For proximal DVTs and PEs, at least 6 months of total therapy is recommended.
  • It is usually more convenient and practical to delay a switch to oral Warfarin for 4 to 6 weeks postpartum.

6.1 LOW MOLECULAR WEIGHT HEPARIN (LMWH)

LMWH has a long half-life and can be given in a single daily subcutaneous dose in most situations. It does not cross the placenta and is not secreted in breast milk. Systematic reviews and NICE have concluded that LMWH is a safe preferred alternative to unfractionated heparin as an anticoagulant during pregnancy.

In a systematic review of LMWH use in pregnancy by Greer and Nelson-Piercy,16 the following associated complicationshave been identified:

  • the incidence of osteoporotic fractures is 0.04% (95% CI 0.01–0.2);however bone scans are not generally indicated
  • the risk of heparin-induced thrombocytopenia is substantially lower with LMWH; checking the platelet count after 10-14 days of treatment is generally acceptable
  • allergic skin reactions may occur in 1.8% (95% CI 1.34–2.37); an alternative LMWH may be indicated, or advice may be sought from the Obstetric Haematology Clinic
  • Significant bleeding, usually related primarily to obstetric causes, occurs in a minority(1.98%; 95% CI 1.5–2.57), both with treatment and prophylactic doses of LMWH; the risk of bleeding is less likely when using prophylactic doses.

6.1.1Therapeutic dosing & monitoring

Tinzaparin (Innohep)175units/kg subcutaneously once daily

  • The dose should be adjusted to achieve a trough and peak (4 hour post-dose) anti-Xa level between 0.4-1.0 units/ml (unless at particularly high risk; see section 4.2.4). The first level can be taken after the third dose when steady state is achieved.
  • Anti-Xa levels provide only a rough guide of the concentration of heparin present and levels provide little or no evidence on the efficacy in relation to prevention of thrombosis.
  • Levels should be checked at least once in each trimester. It may be necessary to convert to a twice daily dose if trough levels are insufficient.

6.1.2 Contraindications to LMWH

Senior input is recommended from the Consultant Obstetrician in conjunction with the Haematologist in managing women in whom LMWH is being considered who themselves are at risk of bleeding:

  • Women with haemophilia or other known bleeding disorder (e.g. von Willebrand’s disease or acquired coagulopathy)
  • Active antenatal or post partum bleeding
  • Women considered at increased risk of major haemorrhage (e.g. placenta praevia)
  • Thrombocytopenia (platelet count < 75 ×109)
  • Acute stroke within previous 4 weeks (haemorrhagic or ischaemic)
  • Severe renal disease (GFR< 30 ml/min/1.73m2)
  • Severe liver disease (prothrombin time above normal range or known varices)
  • Uncontrolled hypertension (BP > 200mmHg systolic or > 120mmHg diastolic)

7.0 FOLLOW UP OF WOMEN WITH ACUTE VTE DURING PREGNANCY OR THE PUERPERIUM

All women diagnosed with an acute VTE during pregnancy should be referred to the Obstetric Haematology clinic and an individual management plan for pregnancy, labour and the postnatal period documented in the handheld records. A copy should be placed in the hospital notes.

Following delivery, the haematology team should review the woman prior to discharge and initial follow up should be made for the Obstetric Haematology clinic. This will be on an individual basis but no later than 6 weeks after delivery.

8.0MONITORING COMPLIANCE

All pulmonary embolism and acute collapse will be detected through the clinical incident reporting system.

Any obstetric patient who develops an acute VTE (either PE or DVT) while an in-patient will be reported as aclinical incident and subject to further investigation.

In addition an audit will be carried out in accordance with the Maternity Services Audit Plan. Auditable standards include:

  • appropriate and timely investigation for suspected VTE in pregnancy and the puerperium.
  • Appropriate management of VTE during pregnancy
  • Management of massive life threatening pulmonary thromboembolism in pregnancy
  • Postnatal follow up of women who have been diagnosed with VTE during pregnancy or postnatal period

Audit results will be presented at the Women’s Services Clinical Governance and Audit meeting and an action plan developed as necessary. A lead will be appointed for monitoring of the action plan, including re-audit, and the status of the action plan reported to the Women’s Services Clinical Governance and Risk management Forum WSCG&RMF) quarterly. Audit results will be included in the Maternity quarterly risk management report and any resulting changes disseminated via the Maternity Services Forum, Team Leaders Forum, Supervisors Forum.

9.0 EVIDENCE BASE

1) Confidential Enquiry into Maternal and Child Health. Saving Mothers’ Lives: Reviewing Maternal Deaths to Make Motherhood Safer, 2003–2005. The Seventh Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom. London: CEMACH; 2007. [ and Perinatal-Health.aspx].

2) Knight M, on behalf of UKOSS. Antenatal pulmonary embolism: risk factors, management and outcomes. BJOG 2008;115: 453–61.

3) James AH, Tapson VF, Goldhaber SZ. Thrombosis during pregnancy and the postpartum period. Am J Obstet Gynecol2005; 193: 216–19.

4) Pomp ER, Lenselink AM, Rosendaal FR, Doggen CJ. Pregnancy, the postpartum period and pro-thrombotic defects: risk of venous thrombosis in the MEGA study. J Thromb Haemost 2008; 6:632–7.

5=3) Francalanci I, Comeglio P, Alessandrello Liotta A, Cellai AP, Fedi S, Parretti E, Mecacci, et al. D-dimer plasma levels during normal pregnancy measured by specific ELISA. Int J Clin Lab Res. 1997; 27:65-7.

6) Daniel KR, Jackson RE, Kline JA. Utility of lower extremity venous ultrasound scanning in the diagnosis and exclusion of pulmonary embolism in outpatients. Ann Emerg Med 2000; 35:547–54.