Prof Aboubakr Elnashar

Aboubakr Elnashar

•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 unreliable

in pregnancy

Aboubakr Elnashar

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.

Aboubakr Elnashar

Outline Diagnosis

•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 Post-thrombotic leg syndrome

Aboubakr Elnashar

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.

Aboubakr Elnashar

Diagnosis of DVT

Compression duplex US

Positive

Continue AC

Negative

High C Susp

Continue AC

US after w

Negative

Discontinue AC

Low C susp

Discontinue AC

Aboubakr Elnashar

Aboubakr Elnashar

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

Aboubakr Elnashar

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.

Aboubakr Elnashar

Aboubakr Elnashar

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

is definitively excluded.

Aboubakr Elnashar

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.

Aboubakr Elnashar

Posteroanterior & lateral chest radiograph:

Findings are normal, usual finding in patients with PTE

Aboubakr Elnashar

Posteroanterior roentgenogram of chest:

Rt lower lobe consolidation & Rt pleural effusion.

Aboubakr Elnashar

•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.

Aboubakr Elnashar

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).

2. May not identify small peripheral PTE. 3. Iodinated contrast medium can potentially alter fetal or

neonatal thyroid function: Thyroid function should be

checked in the neonate.

Aboubakr Elnashar

Aboubakr Elnashar

CT PA:

subsegmental embolus in posterobasal segment

of the rt lower lobe Aboubakr Elnashar

CT PA:

thrombus (arrowed) in the main pulmonary artery at the saddle

extending across the origin of both right and left pulmonary

arteries.

Aboubakr Elnashar

Spiral CT:

Thrombus can be seen as spots where the contrast

medium (bright white in this picture) is missing.

Aboubakr Elnashar

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

Aboubakr Elnashar

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

Aboubakr Elnashar

High-probability perfusion lung scan:

segmental perfusion defects in the right upper

lobe & subsegmental perfusion defects in right

lower lobe, left upper lobe, and left lower lobe. Aboubakr Elnashar

Radiation (uGy)

<10 Chest X ray

<500 Limited venography

3140 Unilateral venography

without abdominal

shield

60-120 Perfusion lung scan

(technetium 99m)

40-90

10-350

Ventillation lung scan

Xenon-133

Technetium 99m

60-1000 CT PA

<500

2210-3740

Pulmonary angiography

Brachial route

Femoral route

Estimated radiation to the fetus

Maximum recommended exposure in pregnancy= 5 rad= 50 000 uGy

1 rad= 10 000 uGy

Aboubakr Elnashar

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:

1. Physiological changes in the coagulation system:

levels become ‘abnormal’ at term & in the postnatal

period.

2. Pre-eclampsia.

-low level: likely to suggest that there is no VTE.

Should not be performed to diagnose acute VTE in

pregnancy

Aboubakr Elnashar

Aboubakr Elnashar

Baseline blood investigations

1. 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}.

Aboubakr Elnashar

Effects of pregnancy & thrombus on the results of a

thrombophilia screen:

1. Protein S levels: fall in normal pregnancy: extremely

difficult to make a diagnosis of protein S deficiency

during pregnancy.

2. Activated protein C (APC) resistance is found with the

APC sensitivity ratio test in 40% of pregnancies

{physiological changes in the coagulation system}.

3. Antithrombin: reduced when extensive thrombus is

present, e.g. nephrotic syndrome & pre-eclampsia

4. Protein C and S: reduced in liver disease

Aboubakr Elnashar

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).

Aboubakr Elnashar

•ADVANTAGES OF LMWHS OVER UFH:

1.More effective

2. Lower:

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.

Aboubakr Elnashar

•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

Aboubakr Elnashar

Monitoring LMWH therapy

1. 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).

Aboubakr Elnashar

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.

1. 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 started at 18

units/kg/h Aboubakr Elnashar

Monitoring:

1. 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 0.5–1.0

units/ml for women with life-threatening PTE). Aboubakr Elnashar

Aboubakr Elnashar

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

2. Fetal deaths (1.7%).

No maternal deaths have been reported..

Aboubakr Elnashar

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.

Aboubakr Elnashar

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.

Aboubakr Elnashar

•Early mobilisation with compression therapy

1. Does not increase developing of PTE: no need for

bed rest in a stable patient on anticoagulant

treatment with acute DVT.

2. Pain & swelling improved faster

3. Prevent post-thrombotic syndrome.

•Compression stockings.

I. Below-knee: for patients without thigh or knee

swelling.

II. 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. Aboubakr Elnashar

•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.

Aboubakr Elnashar

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 pregnant

women at increased risk of bleeding or osteoporosis

Aboubakr Elnashar

•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.

Aboubakr Elnashar

Risk factors for recurrence:

1. Pregnancy-related changes in the coagulation

system

2. Reduced venous flow velocity

3. Thrombophilia (in at least 50%)

4. 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:

1. osteoporosis & fractures.

2. Allergic skin reactions: may require the heparin

preparation to be changed.

Aboubakr Elnashar

Oral anticoagulants

should not be used for antenatal VTE

treatment.

cross the placenta

1. Characteristic embryopathy in the first

trimester,

2. CNS abnormalities which occur during any

trimester

3. Fetal hge and neonatal hge following the

trauma of delivery.

Aboubakr Elnashar

•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.

Aboubakr Elnashar

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).

Aboubakr Elnashar

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.

Aboubakr Elnashar

1.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.

2.Heparin or oral anticoagulant:

a. Neither heparin (UFH or LMWH) nor warfarin is

contraindicated in breastfeeding.

b. 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

Aboubakr Elnashar

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).

Aboubakr Elnashar

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.

Aboubakr Elnashar

•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

Aboubakr Elnashar

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.

Aboubakr Elnashar

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

Aboubakr Elnashar

Aboubakr Elnashar