Bayer Pharma AG

Essence of this Article

The incidence of venous thromboembolism (VTE) in pregnant women is significantly higher than in women of a similar age who are not pregnant. Risk associated with VTE is primarily a result of hypercoagulability induced by hormonal changes. Important risk factors to consider include: increased venous stasis; pregnancy and delivery complications; a personal history of thrombosis; and inherited or acquired thrombophilia. The risk of recurrent VTE in pregnancy is also high. Diagnosis of deep vein thrombosis (DVT) in pregnant patients is usually performed by compression ultrasonography in parallel with D-dimer testing.

Pregnancy increases the risk of venous thromboembolism

The incidence of VTE may be up to five times higher in pregnant women than in women of a similar age who are not pregnant, and the risk of VTE increases by approximately 20-fold during the postpartum period.254, 255 Furthermore, VTE accounts for approximately 1.1 deaths per 100,000 deliveries.256 Risk associated with VTE is primarily a result of hypercoagulability induced by hormonal changes, which can be present as early as the first trimester.254, 257

During pregnancy, concentrations of coagulation factors (Factors I, VII, VIII, IX, X, XI and XII) and resistance to activated protein C increase, whereas concentrations of protein S and antithrombin decrease. Fibrinolytic inhibitors derived from the placenta, such as plasminogen activator inhibitor type-1 (PAI-1) and inhibitor type-2 (PAI-2), also increase. These changes heighten the risk of VTE during pregnancy258, 259

Factors contributing to increased incidence of VTE during pregnancy258

  • Increased levels of coagulation factors (Factor I, VII, VIII, IX, X, XI and XII)
A decrease in the amount of natural anticoagulants
  • Increase in resistance to activated protein C
  • Decreased concentrations of protein S and antithrombin
Increased venous stasis
  • Decreased venous capacitance
  • Increased intravascular volume
  • Obstruction of inferior vena cava
Vascular damage
  • Related to vaginal and caesarean delivery
Source: Bagaria SJ, Bagaria VB (2011). VTE, venous thromboembolism.


Increased venous stasis is the most constant predisposing risk factor for VTE during pregnancy.258, 260 Pregnancy and delivery complications have been reported to further elevate VTE risk. These complications include multiple births, pre-eclampsia, caesarean delivery, postpartum bleeding and blood transfusion.261, 262

Risk factors for VTE during pregnancy

A personal history of thrombosis and inherited or acquired thrombophilia are important risk factors for VTE during pregnancy.261

Other risk factors include:

  • Heart disease
  • Well-recognized general VTE risk factors such as reduced mobility and obesity
  • Haematological disorders such as sickle cell disease
  • Systemic disorders such as lupus
  • Miscellaneous factors such as age (>35 years) and smoking261

Risk of recurrent VTE in pregnancy

The risk of recurrent VTE in pregnancy is high. Rates of recurrence have been shown to range from 2.4% to 12.2% in women who do not receive prophylaxis and from 0.0% to 2.4% in those who do receive prophylaxis.263 Although women with pregnancy-associated VTE have a significantly lower risk of recurrence than women with an unprovoked VTE, the risk of recurrence during subsequent pregnancies is higher.264

In a cohort of 1104 women with previous VTE who did not receive anticoagulation, recurrent VTE occurred in 7.5% of pregnant women in whom the first VTE was unprovoked or was related to pregnancy or oral contraceptive use.265 No recurrence occurred if the first VTE was related to other transient risk factors. In the postpartum period, an increased risk of recurrence was associated with:

  • Pregnancy-related first VTE
  • Carriers of Factor V Leiden

Diagnosis of VTE during pregnancy

During pregnancy, symptoms of VTE, including tachycardia, leg swelling, tachypnoea and dyspnoea, can already be present as a response to physiological changes that occur. Therefore, clinical surveillance for VTE is required.258

Diagnosis of DVT in pregnant patients is usually performed by compression ultrasonography, which is highly sensitive and specific in general VTE populations. If results are normal, tests should be repeated (at days 1–2 after referral and again 1 week later) to exclude the possibility of extending calf DVT.

Because of the potential elevation of D-dimer levels during pregnancy, this test should be performed in parallel with ultrasonography for appropriate diagnosis of DVT.258, 266 Nevertheless, D-dimer testing may help to exclude a diagnosis of DVT.

Magnetic resonance imaging (MRI), or a limited venogram, are alternative options for diagnosis of DVT if the results of compression ultrasonography are inconclusive.266

Ventilation/perfusion scanning is the recommended approach for diagnosis of pulmonary embolism (PE) in non-pregnant patients. Non-diagnostic lung scans should warrant compression ultrasonography, which, along with D-dimer, computed tomography pulmonary angiography or serial ultrasonography may confirm or exclude a diagnosis of PE.258, 266

Methods such as venography, ventilation/perfusion scanning and computed tomography pulmonary angiography are associated with a risk of radiation exposure to the foetus, and appropriate precautions should be considered, such as:258, 266

  • Placement of a lead shield over the abdomen
  • Minimizing fluoroscopy
  • Reduction of the dose of radioisotopes used to perform lung scans266

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