J.M.
Venous thromboembolism
Date 2nd Semester
23.2.2025
Presenter name: assisted prof. dr Shameem alaasam
Venous thromboembolic disease (VTE) is the most common cause of
direct maternal death in the world.
In the most recent triennium, a maternal mortality rate of 1.94 per 100
000 – more than twice that of the next most common cause (pre-
eclampsia).
Physiological changes in pregnancy
Pregnancy is a hypercoagulable state because of an alteration in the
thrombotic and fibrinolytic systems.
There is an increase in clotting factors VIII, IX, X and fibrinogen levels,
and a reduction in protein S and anti-thrombin (AT) III concentrations.
The net result of these changes is thought to be an evolutionary
response to reduce the likelihood of haemorrhage following delivery.
These physiological changes predispose a woman to thromboembolism
and this is further exacerbated by venous stasis in the lower limbs due
to the weight of the gravid uterus placing pressure on the inferior vena
cava in late pregnancy and immobility, particularly in the puerperium.
Pregnancy is associated with a 6–10-fold increase in the risk of venous
thromboembolic disease compared to the non-pregnant situation.
Without thromboprophylaxis, the incidence of non-fatal pulmonary
embolism (PE) and deep vein thrombosis (DVT) in pregnancy is about
0.1 per cent in developed countries, this increases following delivery to
around 1–2 per cent and is further increased following emergency
Caesarean section.
Risk factors for thromboembolic disease
Pre-existing Spesific to pregnancy
• Maternal age(>35 years) • Multiple gestation
• Thrombophilia • Pre-eclampsia
• Obesity(>80 kg) • Grandmultiparity
• Previous thromboembolism • Caesarean section,especially if
• Severe varicose vein emergency
• Smocking • Damage to pelvic vein
• malignancy • Sepsis
• Prolonged bed rest
Thrombophilia
Some women are predisposed to thrombosis through changes in the
coagulation/fibrinolytic system that may be inherited or acquired.
There is growing evidence that both heritable and acquired
thrombophilia's are associated with a range of adverse pregnancy
outcomes particularly recurrent fetal loss.
The major hereditary forms of thrombophilia
currently recognized include
• deficiencies of the endogenous anticoagulants protein C, protein S
and AT III;
• abnormalities of procoagulant factors, factor V Leiden (caused by a
mutation in the factor V gene) and the prothrombin mutation
G20210A.
• It seems probable that there are still some thrombophilia's not yet
discovered or described.
• Heritable thrombophilia's are present in at least 15 per cent of
Western populations.
Acquired thrombophilia is most commonly associated with
antiphospholipid syndrome (APS).
APS is the combination of lupus anticoagulant with or without anti-
cardiolipin antibodies, with a history of recurrent miscarriage and/or
thrombosis. It may (or, more commonly, may not) be associated with
other autoantibody disorders, such as systemic lupus erythematosus
(SLE).
If thrombophilic disorders are taken together, more than 50 per cent of
women with pregnancy- related VTE will have a thrombophilia.
It is therefore vital that women with a history of thrombotic events are
screened for thrombophilia.
The presence of thrombophilia, with a history of thrombotic
episode(s), means that prophylaxis should be considered for pregnancy.
Diagnosis of acute venous thromboembolism
Clinical diagnosis of VTE is unreliable, therefore women who are
suspected of having a DVT or PE should be investigated promptly.
Deep vein thrombosis
The most common symptoms are pain in the calf with varying degrees
of redness or swelling. Women’s legs are often swollen during
pregnancy; therefore, unilateral symptoms should ring alarm bells. The
signs are few, except that often the calf is tender to gentle touch.
It is mandatory to ask about symptoms of PE, as a woman with PE
might present initially with a DVT.
• Compression ultrasound has a high sensitivity and specificity in
diagnosing proximal thrombosis in the non-pregnant woman and
should be the first investigation used in a suspected DVT. Calf veins
are often poorly visualized, however, it is known that a thrombus
confined purely to the calf veins with no extension is very unlikely to
give rise to a PE.
• Venography is invasive, requiring the injection of contrast medium
and the use of x-rays. It does, however, allow excellent visualization of
veins both below and above the knee.
Pulmonary embolus
It is crucial to recognize PE, as missing the diagnosis could have fatal
implications. The most common presentation is of mild breathlessness,
or inspiratory chest pain, in a woman who is not cyanosed but may be
slightly tachycardic (>90 bpm) with a mild pyrexia (37.5oC). Rarely,
massive PE may present with sudden cardiorespiratory collapse .
• If PE is suspected, initial electrocardiogram (ECG), chest x-ray and
arterial blood gases should be performed to exclude other respiratory
diagnoses. However, these investigations are insufficient on their own
to exclude or diagnose PE and it may be sensible to investigate the
lower limbs for evidence of DVT by ultrasound and if positive treat
with a presumptive diagnosis of PE.
• If all the tests are normal but a high clinical suspicion of PE remains, a
ventilation perfusion (V/Q) scan or computed tomography pulmonary
angiogram (CTPA) should be performed. In both cases the radiation to
the fetus is below the threshold considered safe.
• d-dimer is now commonly used as a screening test for thromboembolic
disease in non-pregnant women, in whom it has a high negative
predictive value.
• Out with pregnancy, a low level of d-dimer suggests the absence of a
DVT or PE, and no further objective tests are necessary, while an
increased level of d-dimer suggests that thrombosis may be present and
an objective diagnostic test for DVT and/or PE should be performed.
• In pregnancy, however, d-dimer can be elevated due to the
physiological changes in the coagulation system, limiting its clinical
usefulness as a screening test in this situation.
Treatment of VTE
• Warfarin is given orally and prolongs the prothrombin time (PT).
Warfarin is rarely recommended for use in pregnancy (exceptions
include women with mechanical heart valves) as it crosses the
placenta and can cause limb and facial defects in the first trimester
and fetal intracerebral haemorrhage in the second and third
trimesters.
• Low molecular weight heparins (LMWHs) are now the treatment of
choice. They do not cross the placenta and have been shown to be at
least as safe and effective as unfractionated heparin (UFH) in the
treatment of VTE with lower and fewer haemorrhagic complications
in the initial treatment of non-pregnant subjects. In addition, LMWH
is safe and easy to administer.
• Women are taught to inject themselves and can continue on this
treatment for the duration of their pregnancy.
• Following delivery, women can choose to convert to warfarin (with
the need for stabilization of the doses initially and frequent checks of
the international normalized ratio (INR) or remain on LMWH. Both
warfarin and LMWH are safe in women who are breastfeeding.
• Graduated elastic stockings should be used for the initial treatment of
DVT and should be worn for two years following a DVT to prevent
post phlebitic syndrome which is chronic venouse insufficiency leads
to leg discomfort, swelling, skin rash, discoloration, and/or ulcer.
Prevention of VTE in pregnancy and postpartum
• The Royal College of Obstetricians and Gynaecologists have recently
released updated guidelines on the prevention of thrombosis and
embolism in pregnancy and the puerperium (Green- top Guideline
No. 37, November 2009) and these are summarized below.