Acute management of thromboembolism disease in pregnancy and puerperium

Acute management of thromboembolism disease in pregnancy and puerperium

Dr Funmi Odusoga MRCOG

Table of content

1. Introduction and epidemiology

2. Signs and symptoms

3. Diagnosis and Investigations

4. Treatment

5. Life threatening pulmonary embolism in pregnancy and puerperium

6. Indication for inferior vena cava filter

7. Maintenance treatment

8. Management during labour

9. Postnatal anticoagulation

10. Prevention of post thrombotic syndrome

11. References

Introduction and epidemiology

• The prevalence of ultimately diagnosed PE in pregnant women with suspected PE is 2–6%.
• The risk of antenatal VTE is four- to five-fold higher in pregnant women than non-pregnant women of the same age
• Absolute risk is low at 1 in 1000 pregnancies
• The puerperium is the time of highest risk

Signs and symptoms

• Deep Vein Thrombosis-leg pain and swelling (usually unilateral) and lower abdominal pain (reflecting extension of thrombus into the pelvic vessels and/or development of a collateral circulation)
• Iliac vein thrombosis-back and buttock pain and swelling of the entire limb
• Pulmonary embolism-dyspnoea, chest pain, haemoptysis and collapse.
• Low grade pyrexia and leucocytosis can occur in venous thromboembolism

Diagnosis and Investigations

Note: Any woman with symptoms and/or signs suggestive of VTE should have objective testing performed expeditiously and treatment with low-molecular-weight heparin (LMWH) given until the diagnosis is excluded by objective testing, unless treatment is strongly contraindicated

• If DVT remains untreated, 15–24% of these patients will develop PE.
• 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 event

Investigation

• Compression duplex ultrasound when DVT is suspected-If duplex USS is negative and clinical suspicion is high stop anticoagulation treatment and repeat duplex USS on day 3 and day 7
• Magnetic resonance venography or conventional contrast venography may be considered for Iliac vein thrombosis
• Do ECG-the most common abnormalities were T wave inversion (21%), S1 Q3 T3 pattern

(15%) and right bundle branch block (18% during pregnancy and 4.2% in the puerperium).

• Chest X-ray
• If PE is suspected and there are signs and symptoms of DVT and Doppler USS is positive continue anticoagulation treatment without further investigation for PE
• Do Ventilation perfusion scan VQ scan or computerised tomography pulmonary angiogram (CTPA) if PE is suspected
• CTPA is preferred if Chest x-ray is abnormal
• VQ scan has a slight risk of childhood cancer
• CTPA has a slight risk of breast cancer-life time risk of 13.6% above her background risk with delivery of 10mGy radiation. Use of bismuth shields placed over the breasts reduces risk by 20-40%
• Do not perform D-Dimer test for VTE in pregnant women
• Full blood count, coagulation screen, urea and electrolytes, and liver function tests should be performed before anticoagulation therapy
• Do not perform thrombophilia screen
• Arterial blood analysis is of limited diagnostic value

Treatment

• Administer low-molecular-weight heparin (LMWH) immediately PE or DVT is suspected except when LMWH is contraindicated
• LMWHs are more effective, are associated with a lower risk of haemorrhagic complications and are associated with lower mortality than unfractionated heparin in the initial treatment of DVT in non-pregnant women
• LMWH do not cross the placenta
• LMWH are not associated with increased risk of post-partum haemorrhage
• Heparin induced thrombocytopenia is lower in LMWH than unfractionated heparin
• Offer alternative anticoagulation if patient is allergic to LMWH e.g. fondaparinux, argatroban or r-hirudin
• Give dose titrated against the woman’s booking weight
• Dose of LMWH can be once or twice daily

Initial dose of enoxaparin is determined as follows:

Initial dose of dalteparin is determined as follows

• Lower doses of LMWH should be employed if the creatinine clearance is less than 30 ml/minute (enoxaparin and dalteparin) or less than 20 ml/minute with tinzaparin
• Do peak anti-Xa activity only for extremes of body weight i.e. <50kg and 90kg or more
• In patients on unfractionated heparin Platelet count monitoring should be performed every 2–3 days from days 4 to 14 or until heparin is stopped. Platelet count is not necessary in patient on LMWH

Management of life threatening pulmonary embolism in pregnancy and puerperium

Massive PE may present with shock, refractory hypoxaemia and/or right ventricular dysfunction on echocardiogram and is a medical emergency

• Management should involve a multidisciplinary team (MDT) including senior physicians, obstetricians and radiologists.
• MDT should decide on an individual basis whether a woman receives intravenous unfractionated heparin, thrombolytic therapy or thoracotomy and surgical embolectomy
• Intravenous unfractionated heparin is the preferred, initial treatment in massive PE because of its rapid effect, extensive experience of its use in this situation and since it can be adjusted more readily if thrombolytic therapy is administered
• Do urgent portable echocardiogram or CTPA within 1hour of presentation in patient with signs and symptoms suspicious of life threatening PE
• If massive PE is confirmed or in extreme circumstances prior to confirmation immediate thrombolysis should be considered (be sure there is no intraabdominal bleeding)
• If woman is in cardiac arrest do cardiopulmonary resuscitation in left lateral tilt position and perform perimortem caesarean section by 5minutes if resuscitation is unsuccessful
• If the patient is not suitable for thrombolysis or is moribund, a discussion with the cardiothoracic surgeons with a view to urgent thoracotomy should be had

Dose of unfractionated heparin

• Loading dose of 80 units/kg, followed by a continuous intravenous infusion of 18 units/kg/hour
• if a patient has received thrombolysis, the loading dose of heparin should be omitted and an infusion started at 18 units/kg/hour
• Measure activated partial thromboplastin time (APTT) level 4–6 hours after the loading dose, 6 hours after any dose change and then at least daily when in the therapeutic range.
• The therapeutic target APTT ratio is usually 1.5–2.5 times the average laboratory control value

Additional management in acute DVT and PE

• Elevate leg, apply graduated elastic compression stocking and mobilisation

Indication for inferior vena cava filter

• Peripartum period for patients with iliac vein VTE to reduce the risk of PE
• Patients with proven DVT and who have recurrent PE despite adequate anticoagulation.

Main complications associated with vena cava filters are migration, an increased risk of lower limb DVT and caval thrombosis and, rarely, infection

Maintenance treatment

• Administer therapeutic dose of LMWH for the remainder of the pregnancy and for at least 6weeks post delivery
• Give at least 3months of LMWH in total

Further advice

• Warfarin should not be used for anticoagulation in the antenatal period; it crosses the placenta and is associated with adverse pregnancy outcomes including miscarriage, prematurity, low birthweight, neurodevelopmental problems and fetal and neonatal bleeding. They are also associated with a characteristic embryopathy following fetal exposure in the first trimester
• Consider newer anticoagulants (fondaparinux, argatroban or r-hirudin) in pregnant women who are unable to tolerate heparin (LMWH or unfractionated heparin) or danaparoid and who require continuing anticoagulant therapy.

Management during labour

• Consider unfractionated heparin if VTE is diagnosed at term as it is easily manipulated
• Advise women to stop LMWH immediately she thinks she is going into labour
• Stop LWMH 24 hours before Induction of labour or elective caesarean section
• Do not give spinal or epidural anaesthesia until at least 24 hours after last therapeutic dose of LMWH
• LMWH should not be given for 4 hours after the use of spinal anaesthesia or after the epidural catheter has been removed, and the epidural catheter should not be removed within 12 hours of the most recent injection.
• Consider wound drain after caesarean section and close the skin with interrupted sutures during caesarean section to allow drainage of haematoma
• Unfractionated heparin has a shorter half-life than LMWH and its activity is more completely reversed with protamine sulphate hence use unfractionated heparin for women prone to bleeding e.g. in antepartum haemorrhage, PPH , suspicion of intraabdominal bleeding
• Discuss women with bleeding who are being managed with LMWH with Haematologist

Postnatal anticoagulation

• Offered a choice of LMWH or oral anticoagulant for postnatal therapy after discussion about the need for regular blood tests for monitoring of warfarin, particularly during the first 10 days of treatment.
• Avoid warfarin until at least 5 days post-delivery and longer in those at risk of postpartum haemorrhage
• Heparin and warfarin are not contraindicated in pregnancy
• Continue anticoagulation for longer if the risk of recurrent VTE is considered high

Prevention of post thrombotic syndrome

Post thrombotic syndrome is characterised by chronic persistent leg swelling, pain, a feeling of heaviness, dependant cyanosis, telangiectasia, chronic pigmentation, eczema, associated varicose veins and in the most severe cases, venous ulceration.

• Prolonged use of LMWH reduces the risk of post thrombotic syndrome
• Graduated elastic compression stocking reduces pain and swelling

Reference

1. Summary of RCOG Thrombosis and Embolism during Pregnancy and the Puerperium: Acute Management (Green-top Guideline No. 37b)