Management of Thromboembolic Disease in Pregnancy and Puerperium

1. Prof Aboubakr ElnasharAboubakr Elnashar

2. •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

3. 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

4. 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 syndromeAboubakr Elnashar

5. 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

6. 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

7. Aboubakr Elnashar

8. 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

9. 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

10. Aboubakr Elnashar

11. 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

12. 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

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

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

15. •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

16. 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

17. Aboubakr Elnashar

18. CT PA:
subsegmental embolus in posterobasal segment
of the rt lower lobe
Aboubakr Elnashar

19. 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

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

21. 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

22. 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

23. 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

24. Radiation (uGy)
<10Chest X ray
<500Limited venography
3140Unilateral venography
without abdominal
shield
60-120Perfusion lung scan
(technetium 99m)
40-90
10-350
Ventillation lung scan
Xenon-133
Technetium 99m
60-1000CT 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

25. 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

26. Aboubakr Elnashar

27. 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

28. 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

29. 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

30. •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

31. •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

32. 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

33. 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

34. 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

35. Aboubakr Elnashar

36. 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

37. 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

38. 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

39. •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

40. •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

41. 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

42. •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

43. 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

44. 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

45. •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

46. 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

47. 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

48. 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

49. 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

50. 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

51. •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 persistsAboubakr Elnashar

52. 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

53. 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

54. Thank YouAboubakr Elnashar
Aboubakr Elnashar