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RCOG Guidelines, February

2007
Prof Aboubakr Elnashar
Email: elnashar53@hotmail.com
•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.


Outline
Diagnosis Treatment
•Diagnosis of DVT A. Antenatal
•Diagnosis of PTE •Baseline investigations
1. Chest X-ray •Initial treatment
2. Compression duplex
Doppler
•Monitoring
3. Ventilation–perfusion •Massive life-threatening
lung scan PTE
4. CT pulmonary •Additional therapies
angiogram •Maintenance treatment
5. Alternative •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
1 rad= 10 000 uGy Radiation
(uGy)
Chest X ray <10

Limited <500
venography
Unilateral 3140
venography
without abdominal
shield
Perfusion lung 60-120
scan (technetium
99m)
Ventillation lung
scan 40-90
Xenon-133 10-350
Technetium
CT PA 99m 60-1000

Pulmonary
angiography <500
Brachial route 2210-3740
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 & pre-
eclampsia
•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 post-
thrombotic 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
Thank You
Aboubakr Elnashar

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