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RCOG Guidelines, February2007
Prof Aboubakr ElnasharEmail: [email protected]
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Main direct cause of maternal death in theUK
10 times more common in pregnant thanin nonpregnant
Occur at any stage of pregnancy but thepuerperium is the time of highest risk.
The subjective, clinical assessment is
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DVT is suspected byDVT is suspected by::
Acute leg pain,Acute leg pain,
Swelling, RednessSwelling, Redness
Tenderness.Tenderness.
PTE is suspected byPTE is suspected by
Acute chest painAcute chest pain
Shortness of breath.Shortness of breath.
HaemoptysisHaemoptysis
HypotensionHypotension
Cyanosis occur in massive PTE.Cyanosis occur in massive PTE.
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OutlineDiagnosis
Diagnosis of DVTDiagnosis of PTE1. Chest X-ray2. Compression duplexDoppler3. Ventilationperfusionlung scan4. CT pulmonaryangiogram
5. Alternative
Treatment
A. AntenatalBaseline investigationsInitial treatmentMonitoringMassive life-threateningPTEAdditional therapiesMaintenance treatmentOral anticoagulantB. IntrapartumAnticoagulant in women athigh risk of hge
C. Postnatal
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Any woman with S&S suggestive of VTE should
have objective testing & treatment with LMWHuntil the diagnosis is excluded, unless treatment
is strongly contraindicated.
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Diagnosis of DVT
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:Duplex US
combines Doppler flow information & conventional imaging.information
Shows how blood is flowing through vessels & measures the speed ofblood flow
Estimate the diameter of a blood vessel as well as the amount ofobstruction
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Duplex US: Thrombus with some blood flowing around theclot. (+lack of compressibility of the vein and distal distension duringvalsalva manoeuvre)
The main test used to exclude or diagnose DVT
Simple, painless test with a high degree of accuracy.
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Chest X-rayNormal in over 50%Abnormal features caused by PTE:
AtelectasisEffusionFocal opacities
Regional oligaemia or pulmonary oedema.The radiation dose to the fetus at anystage of pregnancy is negligible.
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Posteroanterior & lateral chest radiograph:
Findings are normal, usual finding in patients with
PTE
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Posteroanterior roentgenogram of chest:
Rt lower lobe consolidation & Rt pleuraleffusion.
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Value:1. May identify other pul disease:pneumonia, pneumothorax or lobar
collapse.2. If abnormal with a high clinical suspicionof PTE: CT PA should be performed.
3. If normal: Bilateral Doppler USlegstudies: diagnosis of DVT may indirectlyconfirm a diagnosis of PTE
{anticoagulant therapy is the same forboth conditions} further investigationunnecessary: limit radiation doses to themother & her fetus.
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CT PAFirst-line investigation for non-massive PTE innonpregnant (Br. Thoracic Soc).
Advantages over radionuclide (V/Q) :1. Better sensitivity & specificity (at least innonpregnant women)2. Lower radiation dose to the fetus (
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CT PA:
subsegmental embolus in posterobasalsegment of the rt lower lobe
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CT PA:
thrombus (arrowed) in the main pulmonary artery at thesaddle extending across the origin of both right and leftpulmonary arteries.
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Spiral CT:
Thrombus can be seen as spots where thecontrast medium (bright white in this picture) ismissing.
V/Q i
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V/Q scanningFirst-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 ofmat breast cancer
Di d t
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:DisadvantageRadiation dose to the foetus is higher than that ofCT PA, (but below the maximum recommended
exposure during pregnancy): slightly increasedrisk of childhood cancer compared with CT PA(1/280,000 Vs
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High-probability perfusion lung scan:
segmental perfusion defects in the rightupper lobe & subsegmental perfusion
defects in right lower lobe, left upper lobe,
Estimated radiation to the fet s
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RadiationRadiation
(uGy)(uGy)
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D-dimer testinga 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 & inthe postnatal period.
11.Pre-eclampsia.-low level: likely to suggest that there is no VTE.Should not be erformed to dia nose acute
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Baseline blood investigations4.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 notroutinely recommended.{Results will not influence immediate
management but it can influence the duration &intensity of anticoagulation, e.g. whenantithrombin deficiency or antiphosphilipidsyndrome is identified}.
Effects of pregnancy & thrombus on the results of
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Effects of pregnancy & thrombus on the results ofa thrombophilia screen:Protein S levels: fall in normal pregnancy:
extremely difficult to make a diagnosis of proteinS deficiency during pregnancy.Activated protein C (APC) resistance is foundwith the APC sensitivity ratio test in 40% of
pregnancies {physiological changes in thecoagulation system}.Antithrombin: reduced when extensive thrombusis present, e.g. nephrotic syndrome & pre-
eclampsiaProtein C and S: reduced in liver disease
Initial anticoagulant treatment of VTE
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Initial anticoagulant treatment of VTEClinically suspected DVT or PTE:LMWH should be given until the diagnosis is
excluded by objective testing, unless treatment isstrongly contraindicated.LMWHs:Do not cross the placenta.
Safe alternative to UFH during pregnancy(Systematic reviews).
Equically effective to UFH in the initial treatmentof PTE (meta-analysis of RCT).
ADVANTAGES OF LMWHS OVER UFH:
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ADVANTAGES OF LMWHS OVER UFH:More effective.1:Lower .2
a. Hgic complicationsb. 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 PPHremains the most common cause of severe obstetric morbidity.
e. Thrombocytopenia
f. Osteoporosis.
Therapeutic dose of LMWH
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Therapeutic dose of LMWH2 SC divided doses with dosage titrated against thewomans booking or most recent weight. (1mg/k,bd)In nonpregnant women, the recommended therapeutic doses of LMWH varies according to themanufacturer (enoxaparin 1.5 mg/kg once daily; dalteparin 10,00018,000 units once dailydepending 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 VTEin 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 inpregnancy, but this has not yet been substantiated with published clinical outcome data on safetyand efficacy in contrast to twice-daily dosing of enoxaparin and dalteparin
Monitoring LMWH therapy
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Monitoring LMWH therapy2.Peak anti-Xa activity:not recommended except in
at extremes of b wt (90 kg)complicating factors (renalimpairment or recurrent VTE).
2. Platelet count: should not becarried out (unless UFH has beengiven).
Management of massive life threatening
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Management of massive life-threateningPTE
Collapsed, shocked
Team of senior physicians, obstetricians &radiologists, who should decide on an individualbasis whether a woman receivesIV UFH, thrombolytic therapy or thoracotomy and
surgical embolectomy.IV UFH:Preferred {rapid effect & extensive experience ofits use in this situation}.
Dose loading dose: 80 units/kg, followed by acontinuous IV infusion of 18 units/kg/h if a woman has received thrombolysis, theloadin dose should be omitted & an infusion
Monitoring:
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Monitoring:2.APTT:46 h after the loading dose, 6 h after any dose
change & then at least daily when in thetherapeutic range.Therapeutic target APTT ratio: 1.52.5 times theaverage laboratory control value.
2. anti-Xa level:In late pregnancy: an apparent heparin resistance{increased fibrinogen & factor VIII, whichinfluence the APTT}: unnecessarily high doses of
heparin: hgic problem: It may be useful todetermine the anti-Xa level as a measure ofheparin dose.With UFH, a lower level of anti-Xa is consideredthera eutic (tar et ran e 0.350.70 units/ml or
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2 An urgent portable echocardiogram or CT PA
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2. An urgent portable echocardiogram or CT PAwithin 1 h of presentation should be arranged.If massive PTE is confirmed or, in extremecircumstances prior to confirmation, immediate
thrombolysis.Indication:Severe PTE with haemodynamic compromise.{more effective than heparin therapy in reducing clot
burden & rapidly improving haemodynamics, but noimpact on long-term survival compared to heparin orLMWH }Types:No agent is superior to the others: streptokinase,urokinase, recombinant tissue plasminogen activator.Side effects:1. Non-fatal maternal bleeding (2.9%). Most aroundcatheter & puncture sites, no reports of intracranial
bleeding
3 If the woman is not suitable for
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3. If the woman is not suitable forthrombolysis or is moribund, a
discussion with the cardiothoracicsurgeons with a view to urgentthoracotomy should be undertaken.
Additional therapies
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Additional therapies1.Leg should be elevated & graduatedelastic compression stocking {reduce
oedema}.2. Mobilization with graduated elasticcompression stockings.
3. Temporary inferior vena caval filter inthe perinatal period for:1. Iliac vein VTE {reduce the risk of PTE}
2. Proven DVT & continuing PTE despiteadequate anticoagulation.
Early mobilisation with compression therapy
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Early mobilisation with compression therapy2.Does not increase developing of PTE: no needfor bed rest in a stable patient on anticoagulant
treatment with acute DVT.3.Pain & swelling improved faster4.Prevent post-thrombotic syndrome.
Compression stockings.Below-knee: for patients without thigh or kneeswelling.Class II: for patients with persisting leg oedema
after DVT.
Class II compression socks & stockings should betaken off at night and do not need to be worn onthe unaffected le .
Leg elevation anticoagulation surgical
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Leg elevation, anticoagulation, surgicalembolectomy 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 theantepartum period, delivery should be
delayed, if possible, to allow maximumtime for anticoagulation rather than puttingin a filter.
Maintenance treatment of VTE
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Maintenance treatment of VTETT continued for the remainder of the pregnancy.LMWH
-clinical assessmentblood platelets & peak anti-Xa levels whenappropriate-Aim:
peak anti-Xa 3 hrs post-injection: 0.51.2units/ml.-Dose:Continuation of therapeutic doses based on the
patients wt (enoxaparin 1 mg/kg 12-hourly;dalteparin 100 units/kg twice daily up to amaximum of 20 000 units/24 hours; tinzaparin175 units/kg)Modified dosin re imen ma be useful in
UFH
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UFH-Platelet count monitored at least everyother 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:
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Risk factors for recurrence:2.Pregnancy-related changes in the coagulationsystem
3.Reduced venous flow velocity4.Thrombophilia (in at least 50%)5.The majority of DVTs in pregnancy areileofemoral, with a greater risk of both
embolisation and recurrence. (In nonpregnant,majority of DVTs are popliteofemoral): longerduration of treatment & treatment throughoutpregnancy.
Prolonged UFH use during pregnancy:8.osteoporosis & fractures.9.Allergic skin reactions: may require the heparinre aration to be chan ed.
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Once labour is established or thinks she is in
labour: No further heparin. Planned delivery or CS: LMWH maintenancetherapy should be discontinued 24 h before.Regional anaesthetic or analgesic techniques:
should not be undertaken until at least 24 h afterthe last dose of therapeutic LMWH.A thromboprophylactic dose of LMWH should begiven by 3 h after CS (>4 h after removal of the
epidural catheter), and the treatment doserecommenced that evening.The epidural catheter: should not be removedwithin 12 h of the most recent injection.
Spontaneous labour in women receiving
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Spontaneous labourin women receivingtherapeutic doses of SC UFH: monitoring of theAPTT : If it is markedly prolonged near delivery,
protamine sulfate may be required to reduce therisk of bleeding.Induction of labour or regional anaesthesia: SCUFH should be discontinued 12 h before & IV UFH
stopped 6 h beforeCS:There is an increased risk of wound haematomawith 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 orinterrupted sutures (allow drainage of anyhaematoma).
Anticoagulant therapy in women at high risk of
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Anticoagulant therapy in women at high risk ofhge
Major antepartum hge
CoagulopathyProgressive wound haematomaSuspected intra-abdominal bleedingPostpartum haemorrhage.
should be managed with IV UFH until the riskfactors for haemorrhage have resolved.{UFH has a shorter half-life than LMWH and itsactivity is more completely reversed with
protamine sulphate}.If a woman develops a hgic problem while onLMWH: treatment should be stopped & experthaematological advice sought.
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Therapeutic anticoagulant therapy: should be
continued for the duration of the pregnancy &for at least 6 w postnatally and until at least 3ms of treatment has been given in total.
Heparin or oral anticoagulant:
e.Neither heparin (UFH or LMWH) nor warfarin iscontraindicated in breastfeeding.
f. WarfarinShould 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
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Before discontinuing treatment, the continuingrisk of thrombosis should be assessed, includinga review of personal and family history of VTE
and any thrombophilia screen results.Arrangements should be made for completion ofthe thrombophilia tests after anticoagulants arestopped; in some units this will be undertaken
in haematology clinics.If the woman chooses to continue with LMWH
postnatally, then either the doses that wereemployed antenatally can be continued or the
manufacturers recommended doses for thenonpregnant patient can be employed(enoxaparin 1.5mg/kg once daily, dalteparin10,00018,000 units once daily depending onbod wei ht, tinza arin 175 units/k once
Daily testing of the international normalised ratio
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y g(INR) is recommended during the transfer fromLMWH to warfarin to avoid over anticoagulation.
The INR should be checked on day 2 of warfarintreatment & subsequent warfarin doses titratedto maintain the INR between 23.
Heparin treatment should be continued until the
INR >2 on 2 successive days.
Prevention of post-thrombotic
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leg syndrome
60% of cases over a median of 4.5years.
Chronic persistent leg swelling,pain, feeling of heaviness,dependent cyanosis, telangiectasis,
chronic pigmentation, eczema,associated varicose veins andchronic ulceration.
Graduated elastic compression
stockings (class II) should be worn onthe affected leg for 2 ys after theacute event, if swelling persists
Symptoms are made worse by standing or
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y p y gwalking & improve with rest and recumbancy.
The syndrome is more common where there is a
recurrent DVT, with obesity and where therehas 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 syndromedecreased from 47% to 20% and severe post-
thrombotic syndrome decreased from 23% to11% with use of compression stockings over 2
y.
Postnatal clinic review
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Postnatal clinic reviewAssessment of post-thromboticvenous damage,Thrombophilia testsAdvice should be given on the need
for thromboprophylaxis in any futurepregnancy & at other times ofincreased risk.
Hormonal contraception should bediscussed
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Thank YouThank YouAboubakr Elnashar
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