Rcog Guidelines, February 2007

RCOG Guidelines, February 2007 Prof Aboubakr Elnashar Email: [email protected]

•Main direct cause of maternal death in the UK •10 times more common in pregnant than in nonpregnant •Occur at any stage of pregnancy but the puerperium is the time of highest risk. •The subjective, clinical assessment is

:DVT is suspected by  Acute leg pain,  Swelling, Redness  Tenderness. PTE is suspected by  Acute chest pain  Shortness of breath.  Haemoptysis  Hypotension  Cyanosis occur in massive PTE.

Diagnosis

Outline

•Diagnosis of DVT •Diagnosis of PTE 1. Chest X-ray 2. Compression duplex Doppler 3. Ventilation–perfusion lung scan 4. CT pulmonary angiogram 5. Alternative

Treatment A. Antenatal •Baseline investigations •Initial treatment •Monitoring •Massive life-threatening PTE •Additional therapies •Maintenance treatment •Oral anticoagulant B. Intrapartum Anticoagulant in women at high risk of hge

C. Postnatal

Any woman with S&S suggestive of VTE should have objective testing & treatment with LMWH until the diagnosis is excluded, unless treatment is strongly contraindicated.

Diagnosis of DVT

:Duplex US combines Doppler flow information & conventional imaging .information Shows how blood is flowing through vessels & measures the speed of  blood flow Estimate the diameter of a blood vessel as well as the amount of obstruction

Duplex US: Thrombus with some blood flowing around the clot. (+lack of compressibility of the vein and distal distension during valsalva manoeuvre)

The main test used to exclude or diagnose DVT Simple, painless test with a high degree of accuracy.

Diagnosis of PTE 1. Chest X-ray: Normal 2. Compression duplex Doppler If both tests are negative with persistent clinical suspicion

3. Ventilation–perfusion (V/Q) lung scan or Computed tomography pulmonary angiogram (CT PA): depend on local availability: Normal but the clinical suspicion is high.

4. Alternative or repeat testing: Anticoagulant treatment should be continued until PTE

Chest X-ray •Normal in over 50% •Abnormal features caused by PTE: Atelectasis Effusion Focal opacities Regional oligaemia or pulmonary oedema. •The radiation dose to the fetus at any stage of pregnancy is negligible.

Posteroanterior & lateral chest radiograph: Findings are normal, usual finding in patients with PTE

Posteroanterior roentgenogram of chest: Rt lower lobe consolidation & Rt pleural effusion.

•Value: 1. May identify other pul disease: pneumonia, pneumothorax or lobar collapse. 2. If abnormal with a high clinical suspicion of PTE: CT PA should be performed. 3. If normal: Bilateral Doppler US leg studies: diagnosis of DVT may indirectly confirm a diagnosis of PTE •{anticoagulant therapy is the same for both conditions} further investigation unnecessary: limit radiation doses to the mother & her fetus.

CT PA First-line investigation for non-massive PTE in nonpregnant (Br. Thoracic Soc). Advantages over radionuclide (V/Q) : 1. Better sensitivity & specificity (at least in nonpregnant women) 2. Lower radiation dose to the fetus (<10% of that with V/Q scanning)

3. Identify other pathology: aortic dissection. Disadvantages: 1. High radiation dose to the maternal breasts. (Breast e is sensitive to radiation during pregnancy: increased lifetime risk by up to 13.6%, background risk of 1/200 for study population).

.May not identify small peripheral PTE .2 Iodinated contrast medium can potentially alter .3 fetal or neonatal thyroid function: Thyroid .function should be checked in the neonate

CT PA: subsegmental embolus in posterobasal segment of the rt lower lobe

CT PA: thrombus (arrowed) in the main pulmonary artery at the saddle extending across the origin of both right and left pulmonary arteries.

Spiral CT: Thrombus can be seen as spots where the contrast medium (bright white in this picture) is missing.

V/Q scanning First-line investigation in pregnancy.((Many authorities :Especially Family history of breast cancer .History of chest CT scan :Advantages 1. High negative predictive value 2. Lower radiation dose to breast: lower risk of mat breast cancer

:Disadvantage Radiation dose to the foetus is higher than that of CT PA, (but below the maximum recommended exposure during pregnancy): slightly increased risk of childhood cancer compared with CT PA (1/280,000 Vs <1/1,000,000) The ventilation component can often be omitted during pregnancy: minimizing the radiation dose for the fetus

High-probability perfusion lung scan: segmental perfusion defects in the right upper lobe & subsegmental perfusion defects in right lower lobe, left upper lobe,

Estimated radiation to the fetus Maximum recommended exposure in pregnancy= 5 rad= 50 000 uGy Radiation 1 rad= 10 000 uGy (uGy) Chest X ray <10 Limited venography Unilateral venography without abdominal shield Perfusion lung

<500

scan Xenon-133 Technetium 99m CT PA

40-90 10-350 60-1000

Pulmonary angiography Brachial route

<500 2210-3740

scan (technetium 99m) Ventillation lung

3140

60-120

D-dimer testing a marker of coagulation or blood clotting • Nonpregnant: Rapid & inexpensive.  Useful for excluding DVT if the results are normal. With highly sensitive assay: false negative: 4% With a moderately sensitive assay: false negative: 17% • Pregnancy: -High level: 10.Physiological changes in the coagulation system: levels become ‘abnormal’ at term & in the postnatal period. 11.Pre-eclampsia. -low level: likely to suggest that there is no VTE. Should not be performed to diagnose acute

Baseline blood investigations 4.Full blood count, coagulation screen, urea & electrolytes & liver function tests. {Anticoagulant therapy can be influenced by renal & hepatic function} 2. Thrombophilia screen prior to therapy is not routinely recommended. {Results will not influence immediate management but it can influence the duration & intensity of anticoagulation, e.g. when antithrombin deficiency or antiphosphilipid syndrome is identified}.

Effects of pregnancy & thrombus on the results of a thrombophilia screen: •Protein S levels: fall in normal pregnancy: extremely difficult to make a diagnosis of protein S deficiency during pregnancy. •Activated protein C (APC) resistance is found with the APC sensitivity ratio test in 40% of pregnancies {physiological changes in the coagulation system}. •Antithrombin: reduced when extensive thrombus is present, e.g. nephrotic syndrome & preeclampsia •Protein C and S: reduced in liver disease

Initial anticoagulant treatment of VTE •Clinically suspected DVT or PTE: LMWH should be given until the diagnosis is excluded by objective testing, unless treatment is strongly contraindicated. •LMWHs: Do not cross the placenta. Safe alternative to UFH during pregnancy (Systematic reviews).

Equically effective to UFH in the initial treatment of PTE (meta-analysis of RCT).

•ADVANTAGES OF LMWHS OVER UFH: More effective.1 :Lower .2 a. Hgic complications b. Mortality than UFH in treatment of DVT . in nonpregnant women((Meta-analyses of RCT c. Recurrent VTE (1.15% for LMWH; 5% for UFH) d. Bleeding. This is important in obstetric practice where PPH remains the most common cause of severe obstetric morbidity.

e. Thrombocytopenia f. Osteoporosis.

•Therapeutic dose of LMWH 2 SC divided doses with dosage titrated against the woman’s booking or most recent weight. (1mg/k, bd) In nonpregnant women, the recommended therapeutic doses of LMWH varies according to the manufacturer (enoxaparin 1.5 mg/kg once daily; dalteparin 10,000–18,000 units once daily depending on body weight; tinzaparin 175 units/kg once daily). In view of recognised alterations in the pharmacokinetics of dalteparin and enoxaparin during pregnancy, a twice-daily dosage regimen is recommended for these LMWHs in the treatment of VTE in pregnancy (enoxaparin 1 mg/kg twice daily; dalteparin 100 units/kg twice daily). Preliminary biochemical data from a relatively small number of women suggests that once-daily administration of tinzaparin (175 units/kg) may be appropriate in the treatment of VTE in pregnancy, but this has not yet been substantiated with published clinical outcome data on safety and efficacy in contrast to twice-daily dosing of enoxaparin and dalteparin

Monitoring LMWH therapy 2.Peak anti-Xa activity: not recommended except in at extremes of b wt (<50 kg & >90 kg) complicating factors (renal impairment or recurrent VTE). 2. Platelet count: should not be carried out (unless UFH has been given).

Management of massive life-threatening PTE Collapsed, shocked Team of senior physicians, obstetricians & radiologists, who should decide on an individual basis whether a woman receives IV UFH, thrombolytic therapy or thoracotomy and surgical embolectomy. •IV UFH: Preferred {rapid effect & extensive experience of its use in this situation}. Dose ● loading dose: 80 units/kg, followed by a continuous IV infusion of 18 units/kg/h ● if a woman has received thrombolysis, the loading dose should be omitted & an infusion

Monitoring: 2.APTT: 4–6 h after the loading dose, 6 h after any dose change & then at least daily when in the therapeutic range. Therapeutic target APTT ratio: 1.5–2.5 times the average laboratory control value. 2. anti-Xa level: In late pregnancy: an apparent heparin resistance {increased fibrinogen & factor VIII, which influence the APTT}: unnecessarily high doses of heparin: hgic problem: It may be useful to determine the anti-Xa level as a measure of heparin dose. With UFH, a lower level of anti-Xa is considered therapeutic (target range 0.35–0.70 units/ml or

2. An urgent portable echocardiogram or CT PA within 1 h of presentation should be arranged. If massive PTE is confirmed or, in extreme circumstances prior to confirmation, immediate thrombolysis. Indication: Severe PTE with haemodynamic compromise. {more effective than heparin therapy in reducing clot burden & rapidly improving haemodynamics, but no impact on long-term survival compared to heparin or LMWH } Types: No agent is superior to the others: streptokinase, urokinase, recombinant tissue plasminogen activator. Side effects: 1. Non-fatal maternal bleeding (2.9%). Most around catheter & puncture sites, no reports of intracranial bleeding

3. 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 1. Leg should be elevated & graduated elastic compression stocking {reduce oedema}. 2. Mobilization with graduated elastic compression stockings. 3. Temporary inferior vena caval filter in the perinatal period for: 1. Iliac vein VTE {reduce the risk of PTE} 2. Proven DVT & continuing PTE despite adequate anticoagulation.

•Early mobilisation with compression therapy 2.Does not increase developing of PTE: no need for bed rest in a stable patient on anticoagulant treatment with acute DVT. 3.Pain & swelling improved faster 4.Prevent post-thrombotic syndrome. •Compression stockings. •Below-knee: for patients without thigh or knee swelling. •Class II: for patients with persisting leg oedema after DVT. Class II compression socks & stockings should be taken off at night and do not need to be worn on the unaffected leg.

•Leg elevation, anticoagulation, surgical embolectomy or thrombolytic therapy: Where DVT threatens leg viability through venous gangrene •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 treatment of VTE •TT continued for the remainder of the pregnancy. •LMWH -clinical assessment blood platelets & peak anti-Xa levels when appropriate -Aim: peak anti-Xa 3 hrs post-injection: 0.5–1.2 units/ml. -Dose: Continuation of therapeutic doses based on the patient’s wt (enoxaparin 1 mg/kg 12-hourly; dalteparin 100 units/kg twice daily up to a maximum of 20 000 units/24 hours; tinzaparin 175 units/kg) Modified dosing regimen may be useful in

•UFH -Platelet count monitored at least every other day until day 14 or until the UFH is stopped, whichever occurs first. -Thrombocytopenia or allergy: heparinoid, danaparoid sodium or fondaparinux, under specialist advice.

Risk factors for recurrence: 2.Pregnancy-related changes in the coagulation system 3.Reduced venous flow velocity 4.Thrombophilia (in at least 50%) 5.The majority of DVTs in pregnancy are ileofemoral, with a greater risk of both embolisation and recurrence. (In nonpregnant, majority of DVTs are popliteofemoral): longer duration of treatment & treatment throughout pregnancy. Prolonged UFH use during pregnancy: 8.osteoporosis & fractures. 9.Allergic skin reactions: may require the heparin preparation to be changed.

Oral anticoagulants should not be used for antenatal VTE treatment. cross the placenta 4.Characteristic embryopathy in the first trimester, 5.CNS abnormalities which occur during any trimester 6.Fetal hge and neonatal hge following the trauma of delivery.

•Once labour is established or thinks she is in labour: No further heparin. • Planned delivery or CS: LMWH maintenance therapy should be discontinued 24 h before. •Regional anaesthetic or analgesic techniques: should not be undertaken until at least 24 h after the last dose of therapeutic LMWH. •A thromboprophylactic dose of LMWH should be given by 3 h after CS (>4 h after removal of the epidural catheter), and the treatment dose recommenced that evening. •The epidural catheter: should not be removed within 12 h of the most recent injection.

Spontaneous labour in women receiving therapeutic doses of SC UFH: monitoring of the APTT : If it is markedly prolonged near delivery, protamine sulfate may be required to reduce the risk of bleeding. Induction of labour or regional anaesthesia: SC UFH should be discontinued 12 h before & IV UFH stopped 6 h before CS: There is an increased risk of wound haematoma with both UFH and LMWH of around 2%. In women receiving therapeutic doses of LMWH: wound drains (abdominal & rectus sheath) skin incision should be closed with staples or interrupted sutures (allow drainage of any haematoma).

Anticoagulant therapy in women at high risk of hge Major antepartum hge Coagulopathy Progressive wound haematoma Suspected intra-abdominal bleeding Postpartum haemorrhage. should be managed with IV UFH until the risk factors for haemorrhage have resolved. {UFH has a shorter half-life than LMWH and its activity is more completely reversed with protamine sulphate}. If a woman develops a hgic problem while on LMWH: treatment should be stopped & expert haematological advice sought.

• Therapeutic anticoagulant therapy: should be continued for the duration of the pregnancy & for at least 6 w postnatally and until at least 3 ms of treatment has been given in total. • Heparin or oral anticoagulant: e.Neither heparin (UFH or LMWH) nor warfarin is contraindicated in breastfeeding. f. Warfarin Should be avoided until 3rd day & for longer in women at increased risk of postpartum hge. Regular blood tests for monitoring, particularly during the first 10 days of treatment

Before discontinuing treatment, the continuing risk of thrombosis should be assessed, including a review of personal and family history of VTE and any thrombophilia screen results. Arrangements should be made for completion of the thrombophilia tests after anticoagulants are stopped; in some units this will be undertaken in haematology clinics. If the woman chooses to continue with LMWH postnatally, then either the doses that were employed antenatally can be continued or the manufacturers’ recommended doses for the nonpregnant patient can be employed (enoxaparin 1.5mg/kg once daily, dalteparin 10,000–18,000 units once daily depending on body weight, tinzaparin 175 units/kg once

Daily testing of the international normalised ratio (INR) is recommended during the transfer from LMWH to warfarin to avoid over anticoagulation. The INR should be checked on day 2 of warfarin treatment & subsequent warfarin doses titrated to maintain the INR between 2–3. Heparin treatment should be continued until the INR >2 on 2 successive days.

•Prevention of post-thrombotic leg syndrome •60% of cases over a median of 4.5 years. •Chronic persistent leg swelling, pain, feeling of heaviness, dependent cyanosis, telangiectasis, chronic pigmentation, eczema, associated varicose veins and chronic ulceration. •Graduated elastic compression stockings (class II) should be worn on the affected leg for 2 ys after the acute event, if swelling persists

Symptoms are made worse by standing or walking & improve with rest and recumbancy. The syndrome is more common where there is a recurrent DVT, with obesity and where there has been inadequate anticoagulation. Graduated elastic compression stockings will improve the microcirculation by assisting the calf muscle pump, reducing swelling and reflux, and reducing venous hypertension. Mild to moderate post-thrombotic syndrome decreased from 47% to 20% and severe postthrombotic syndrome decreased from 23% to 11% with use of compression stockings over 2 y.

Postnatal clinic review •Assessment of post-thrombotic venous damage, •Thrombophilia tests •Advice should be given on the need for thromboprophylaxis in any future pregnancy & at other times of increased risk. •Hormonal contraception should be discussed

Aboubakr Elnashar

Thank You