In addition to these evidence-based recommendations, the guideline development group also identifies points of best clinical practice in the original guideline document.
Levels of evidence (Ia-IV) and grading of recommendations (A-C) are defined at the end of the "Major Recommendations" field.
Diagnosis of Acute Venous Thromboembolism (VTE)
How Is Acute VTE Diagnosed in Pregnancy?
C - Any woman with signs and symptoms suggestive of VTE should have objective testing performed expeditiously and treatment with low-molecular-weight heparin (LMWH) (see section "Initial anticoagulant treatment of VTE in pregnancy" below) until the diagnosis is excluded by objective testing, unless treatment is strongly contraindicated.
What Investigations Are Needed for the Diagnosis of an Acute DVT?
C - Compression duplex ultrasound should be undertaken where there is clinical suspicion of deep venous thrombosis (DVT). If ultrasound is negative and there is a low level of clinical suspicion, anticoagulant treatment can be discontinued.
Compression duplex ultrasound is the primary diagnostic test for DVT. If ultrasound confirms the diagnosis of DVT, anticoagulant treatment should be continued. If ultrasound is negative and a high level of clinical suspicion exists, the woman should remain anticoagulated and ultrasound repeated in 1 week or an alternative diagnostic test employed. If repeat testing is negative, anticoagulant treatment should be discontinued. (Evidence level IV)
When iliac vein thrombosis is suspected (back pain and swelling of the entire limb), magnetic resonance venography or conventional contrast venography may be considered. (Evidence level IV)
What Investigations Are Needed for the Diagnosis of an Acute Pulmonary Thromboembolism (PTE)?
C - Where there is clinical suspicion of acute PTE a chest x-ray should be performed. Compression duplex Doppler should be performed where this is normal. If both tests are negative with persistent clinical suspicion of acute PTE, a ventilation–perfusion (V/Q) lung scan or a computed tomography pulmonary angiogram (CTPA) should be performed.
C - Alternative or repeat testing should be carried out where V/Q scan or CTPA and duplex Doppler are normal but the clinical suspicion of PTE is high. Anticoagulant treatment should be continued until PTE is definitively excluded.
B - Women with suspected PTE should be advised that V/Q scanning carries a slightly increased risk of childhood cancer compared with CTPA (1/280,000 versus less than 1/1,000,000) but carries a lower risk of maternal breast cancer (lifetime risk increased by up to 13.6% with CTPA, background risk of 1/200 for study population).
Chest x-ray may identify other pulmonary disease such as pneumonia, Pneumothorax, or lobar collapse. Whilst the x-ray is normal in over 50% of pregnant women with objectively proven PTE, abnormal features caused by PTE include atelectasis, effusion, focal opacities, regional oligaemia, or pulmonary oedema. The radiation dose to the fetus from a chest x-ray performed at any stage of pregnancy is negligible. If the x-ray is abnormal with a high clinical suspicion of PTE, CTPA should be performed. (Evidence level IV)
If the x-ray is normal, bilateral Doppler ultrasound leg studies should be performed. Although the use of lower-limb Doppler ultrasound in the investigation of PTE has not been validated in pregnancy, there have been several studies investigating its role in nonpregnant women with suspected PTE. A diagnosis of DVT may indirectly confirm a diagnosis of PTE and, since anticoagulant therapy is the same for both conditions, further investigation may not be necessary.This would limit the radiation doses given to the mother and her fetus. (Evidence level IV)
Should D-dimer Testing Be Performed Prior to Objective Diagnosis?
C - D-dimer testing should not be performed to diagnose acute VTE in pregnancy
Baseline Blood Investigations
The use of anticoagulant therapy can be influenced by renal and hepatic function and blood should be taken to confirm that these are normal before starting treatment.
Initial Anticoagulant Treatment of VTE in Pregnancy
What is the Initial Treatment of VTE in Pregnancy?
C - In clinically suspected DVT or PTE, treatment with LMWH should be given until the diagnosis is excluded by objective testing, unless treatment is strongly contraindicated.
What Is the Therapeutic Dose of LMWH in Pregnancy?
See Table 1 in the original guideline document for calculation of initial doses of drugs by early pregnancy weight.
Should Blood Tests Be Performed to Monitor LMWH Therapy in Pregnancy?
If the diagnosis of VTE is confirmed (DVT or PTE), treatment should be continued. Experience indicates that satisfactory anti-Xa levels (peak anti-Xa activity, 3 hours post-injection, of 0.5–1.2 units/mL) are obtained using a weight-based regimen and monitoring of anti-Xa is not routinely required in women with VTE on therapeutic doses of LMWH, particularly as there are concerns over the accuracy of anti-Xa monitoring. There may be a case for monitoring levels at extremes of body weight (less than 50 kg and 90 kg or more) and women with other complicating factors, including renal disease and recurrent VTE.
Guideline documents recommend that routine platelet count monitoring is not required in obstetric women who have received only LMWH as there have been no cases of heparin-induced thrombocytopenic thrombosis in pregnancies managed with LMWH. If unfractionated heparin is employed, or if the obstetric patient is receiving LMWH after first receiving unfractionated heparin, or if she has received unfractionated heparin in the past, the platelet count should ideally be monitored every 2 to 3 days from day 4 to day 14 or until heparin is stopped, whichever occurs first.
How Should Massive Life-Threatening PTE in Pregnancy be Managed?
B - Intravenous unfractionated heparin is the preferred treatment in massive PTE with cardiovascular compromise.
In massive life-threatening PTE with haemodynamic compromise there is a case for considering thrombolytic therapy, as anticoagulant therapy will not reduce the obstruction of the pulmonary circulation. After thrombolytic therapy has been given, an infusion of unfractionated heparin can be given but the loading dose should be omitted.
If the woman is not suitable for thrombolysis or is moribund, a discussion with the cardiothoracic surgeons with a view to urgent thoracotomy should be undertaken.
Additional Therapies
What Additional Therapies Should Be Employed in the Management of VTE in Pregnancy?
Pain and swelling in the affected leg are debilitating symptoms of DVT. Short-term studies in patients with proximal DVT showed that pain and swelling improved faster in mobile patients wearing compression hosiery than in those resting in bed without any compression. This approach can also prevent the development of post-thrombotic syndrome.
There is evidence that the use of an inferior vena caval filter prior to labour or delivery reduces the risk of PTE. However, when VTE occurs in the antepartum period, delivery should be delayed, if possible, to allow maximum time for anticoagulation rather than putting in a filter.
Maintenance Therapy of VTE
What Is the Maintenance Treatment of DVT or PTE?
B - Treatment with therapeutic doses of subcutaneous LMWH should be employed during the remainder of the pregnancy.
C - Pregnant women who develop heparin-induced thrombocytopenia or have heparin allergy and require continuing anticoagulant therapy should be managed with the heparinoid, danaparoid sodium or fondaparinux, under specialist advice.
Can Oral anticoagulants Be Used During Pregnancy for the Maintenance Treatment of VTE?
C - Because of their adverse effects on the fetus, oral anticoagulants should not be used for antenatal VTE treatment.
Anticoagulant Therapy During Labour and Delivery
Should Anticoagulant Therapy Be Altered During Labour and Delivery?
In order to avoid an unwanted anticoagulant effect during delivery, LMWH should be stopped as soon as a woman is in established labour or thinks she is in labour. For elective delivery, LMWH should be stopped 24 hours before induction of labour or caesarean section. Bleeding complications appear to be very uncommon with LMWH.
Postnatal Anticoagulation
How Should Anticoagulation Be Managed Postnatally?
C - Therapeutic anticoagulant therapy should be continued for the duration of the pregnancy and for at least 6 weeks postnatally and until at least 3 months of treatment has been given in total.
Prevention of Post-thrombotic Leg Syndrome
What Measures Can Be Employed to Prevent the Development of Post-Thrombotic Syndrome?
A - Graduated elastic compression stockings should be worn on the affected leg for 2 years after the acute event, if swelling persists, to reduce the risk of post-thrombotic syndrome.
Postnatal Clinic Review
At the postnatal review, an assessment should be made of post-thrombotic venous damage, thrombophilia tests should be reviewed and arrangements made to repeat them if necessary. Advice should be given on the need for thromboprophylaxis in any future pregnancy and at other times of increased risk. Hormonal contraception should be discussed.
Definitions:
Grading of Recommendations
Grade A - Requires at least one randomised controlled trial as part of a body of literature of overall good quality and consistency addressing the specific recommendation. (Evidence levels Ia, Ib)
Grade B - Requires the availability of well controlled clinical studies but no randomised clinical trials on the topic of recommendations. (Evidence levels IIa, IIb, III)
Grade C - Requires evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities. Indicates an absence of directly applicable clinical studies of good quality. (Evidence level IV)
Levels of Evidence
Ia: Evidence obtained from meta-analyses of randomised controlled trials
Ib: Evidence obtained from at least one randomised controlled trial
IIa: Evidence obtained from at least one well-designed controlled study without randomisation
IIb: Evidence obtained from at least one other type of well-designed quasi-experimental study
III: Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies, and case studies
IV: Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities
