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.......................................................................................................................................................................... 11. Venous thrombo-embolic disease during pregnancy and the puerperium

11.1 Epidemiology and maternal risk

VTE, encompassing PE and deep vein/venous thrombosis (DVT), represents a significant cause of pregnancy-related morbidity and mortality. Pregnancy and the puerperium are associated with an increased incidence of VTE occurring in around 0.05–0.20% of all pregnancies,390–393 and rates of PE of around 0.03%.394,395 PE is the most common cause of direct maternal death in the UK, with an incidence of 1.26 deaths per 100 000 pregnancies, and it is the fifth most common cause of maternal death overall.3 The case fatality rate is 3.5%.396 The risk of VTE is highest in the immediate post-partum period with rates of nearly 0.5% reported,394,397 and returns to the non-pregnant level after the sixth week post-partum.390,394,397 In women with previous VTE, recurrence rates are 7.6%, and in a highrisk population rates are 5.5% despite the use of LMWH.398,399 Consequently, a high index of suspicion and a low threshold for investigation must be maintained in pregnant women in general and in high-risk women specifically. The current background information and detailed discussion of the data for the following section of these Guidelines can be found in ESC CardioMed.

11.2 Risk factors for pregnancy-related

venous thrombo-embolism and risk stratification The presence of one risk factor increases the rate of VTE from 0.02 to 0.05%.397,400 Consequently, all women should undergo a documented assessment of risk factors for VTE before pregnancy or in early pregnancy.401 Based on this, women can be classified as being at high, intermediate, or low-risk of VTE and preventative measures applied accordingly.401 Previous unprovoked recurrent VTEs and previous VTE—unprovoked or oestrogen-related—are considered high-risk factors.

11.3 Prevention of venous thrombo-

embolism Prospective, non-randomized studies have shown that in women with risk factors not receiving anticoagulation, the recurrence rate of VTE ranged from 2.4–12.2%, in comparison with 0–5.5% in patients who did receive anticoagulation.399,402 LMWH has become the drug of choice for the prevention and treatment of VTE in pregnant patients.13 It causes less bone loss than UFH, and the osteoporotic fracture rate is lower (0.04% of pregnant women treated with LMWH).13 The initial dose of LMWH for thromboprophylaxis should be based on the booking weight (body weight at the first antenatal appointment with the gynaecologist, e.g. 8–10 weeks of pregnancy) since weight-based LMWH regimens have been shown to achieve prophylactic anti-Xa levels more effectively.403 Consequently, patients at high-risk for VTE should receive prophylactic enoxaparin at 0.5 IU/kg of body weight once daily403 or another LMWH at equivalent doses, according to local practice. In morbidly obese women, weight-based dosing instead of fixed dosing is more appropriate in order to achieve adequate anti-Xa concentrations.404

11.4 Management of acute venous

thrombo-embolism 11.4.1 Pulmonary embolism 11.4.1.1 Clinical presentation The symptoms and signs of PE during pregnancy are the same as in the non-pregnant state (dyspnoea, chest pain, tachycardia, haemoptysis, and collapse). However, subjective clinical assessment of PE is more difficult because dyspnoea and tachycardia are relatively common in normal pregnancy.

11.4.1.2 Diagnosis Clinical prediction rules for assigning pre-test probabilities of VTE have been validated and diagnostic algorithms established in the nonpregnant patient. These include the use of D-dimer testing, compression ultrasonography, CT pulmonary angiography, and ventilation/ perfusion lung scanning.405 This is not the case in pregnant women.406 A high index of suspicion is important, and all pregnant women with signs and symptoms suggestive of VTE should have objective testing performed urgently and receive therapeutic anticoagulation until the diagnosis is established. D-dimer levels increase physiologically with each trimester. In one study, the mean [standard deviation (SD)] preconception D-dimer concentration was 0.43 (0.49) mg/L, and rose in the first, second, and third trimesters to 0.58 (SD 0.36), 0.83 (SD 0.46), and 1.16 (SD 0.57) mg/L, respectively, indicating a 39% relative increase in D-dimer concentration for each trimester.407 Thus, a positive D-dimer test in pregnancy is not necessarily indicative of VTE and further objective testing is required. A negative D-dimer test helps to exclude VTE outside pregnancy, but normal D-dimer concentrations have been reported in pregnant women with VTE,408 meaning that imaging remains the diagnostic test of choice during pregnancy.409 Currently, the optimal diagnostic approach for the pregnant patient with suspected PE is uncertain.410 A modified Wells score may be useful alone or in combination with D-dimer testing to stratify women into those needing imaging, allowing the remainder to avoid unnecessary radiation exposure,411,412 but this awaits further study. If the index of suspicion of DVT remains high, then compression ultrasound should be performed, and if this is abnormal then anticoagulation is indicated. If compression ultrasonography is negative, then further testing is required and MRI should be performed. Where PE is suspected and all other investigations are normal, low-dose CT should be undertaken.

1.4.1.3 Treatment

LMWH: LMWH has become the drug of choice for the treatment of VTE in pregnancy and the puerperium. In suspected DVT or PE, therapeutic LMWH should be given until the diagnosis is excluded by objective testing. Dosage: The recommended therapeutic dose is calculated on early pregnancy body weight (e.g. enoxaparin 1 mg/kg body weight twice daily, dalteparin 100 IU/kg body weight twice daily, or tinzaparin 175 IU/kg), aiming for 4–6 h peak anti-Xa values of 0.6–1.2 IU/mL.413 Downloaded from academic.oup.com/eurheartj/article/39/34/3165/5078465 by guest on 07 October 2026