Pulmonary embolism is a disease of the pulmonary circulation caused by blockage of the pulmonary artery or its branches by embolic material, including thromboembolism, fat embolism, amniotic fluid embolism, air embolism, etc. The pulmonary embolism discussed here is the most common thromboembolism.
Increased levels of coagulation factors, relatively decreased levels of anticoagulation factors, and reduced fibrinolytic activity during pregnancy put the blood system in a hypercoagulable state. The positive aspect of this physiological change is that it reduces the risk of bleeding during labor, but it also increases the risk of thrombosis. Pulmonary embolism is a serious complication of pregnancy that endangers the life of mother and fetus, with an incidence of 0.09‰ to 0.70‰. It is the main cause of maternal death in developed countries and an important cause of maternal death due to non-obstetric factors in China.
I. High-risk factors and pathogenesis of pulmonary embolism during pregnancy
Pulmonary embolism is a serious complication of venous thromboembolism (VTE). Pulmonary embolism in pregnancy is mainly caused by the dislodgement of thrombus formed in the pelvic and lower limb veins and blockage of pulmonary artery. The high-risk factors for VTE in pregnancy include the following.
(I) Pregnancy
Pregnancy itself is a high-risk factor for pulmonary embolism. The risk of both arterial embolism and venous embolism increases during pregnancy, but venous embolism is predominant, accounting for about 80% of cases, and mostly lower extremity (left lower extremity is more common) and pelvic vein embolism. In addition to the physiological factor that maternal blood is hypercoagulable, the presence of various factors such as increased venous blood volume during pregnancy, slow venous blood flow, compression of the pelvic veins by the pregnant uterus, and reduced activity of pregnant women increases the risk of VTE during pregnancy by 7-10 times compared to non-pregnant women of the same age.
(II) Acquired embolism prone disorder
Acquired embolism includes autoimmune diseases, such as antiphospholipid syndrome and systemic lupus erythematosus; hematologic diseases, such as erythrocytosis and thrombocytosis; endocrine diseases, such as diabetes mellitus and Cushing syndrome; and nephrotic syndrome, liver disease and malignancy. Pregnant women with antiphospholipid syndrome and systemic lupus erythematosus are prone to recurrent miscarriages, and once a successful pregnancy is achieved, they also become a high-risk group for embolic diseases during pregnancy.
(C) Hereditary embolic disorders
There are obvious racial differences in hereditary diseases, such as Leiden mutation of coagulation factor V gene, MTHFR gene mutation, and prothrombin gene mutation, which are highly prevalent in Caucasians, especially Caucasians, and very rare in Chinese; and hereditary protein C and protein S defects are important risk factors for venous thrombosis in Chinese. These hereditary alterations enhance coagulation and weaken fibrinolysis, imbalance the coagulation-fibrinolysis system, and intravascular thrombosis, thus causing a series of complications during pregnancy.
(iv) Other factors
Other high-risk factors for pulmonary embolism during pregnancy include.
(1) History of venous thrombosis or pulmonary embolism: it is the most important risk factor for pulmonary embolism or (deep venous thrombosis, DVT) in pregnancy, and the risk of developing it in another pregnancy is significantly increased, and about 1/3 of pregnant women who develop venous embolism in pregnancy have a previous history of embolism.
(2) Obesity: the risk of VTE increases two to three times when body mass index is >30, and the risk is higher in those with severe obesity (body mass index >40).
(3) Braking or sedentary: One study found a 2-fold increased risk of venous embolism in the weeks following a long trip (more than 4 h of continuous transportation).
(4) Excessive intake of red meat or processed meat, insufficient intake of fruits and vegetables, etc.
The above factors, especially the presence of hereditary or acquired vulnerability to embolism, significantly increase the risk of VTE during pregnancy, and about 50% of patients with thromboembolism in pregnancy have hereditary or acquired vulnerability to embolism.
II. Prevention of pulmonary embolism in pregnancy
Considering the high risk of pulmonary embolism during pregnancy in women with thrombophilia and the serious sequelae caused by pulmonary embolism during pregnancy to the mother and fetus, preventive anticoagulation therapy is often administered to some high-risk pregnant women. It has been reported that the risk of recurrence of VTE or pulmonary embolism in pregnancy without prophylactic anticoagulation therapy ranges from 2.4% to 12.2%, while the recurrence rate of VTE can be reduced to 0%-2% in those with prophylactic anticoagulation therapy.
Due to the specificity of pregnancy, prophylactic anticoagulation may also have adverse effects on the mother and fetus. Therefore, do women with embolism-prone pregnancies benefit from prophylactic anticoagulation? What are the indications for anticoagulation? How should the treatment plan be developed? What are the side effects of different treatment regimens? Answers to these questions require additional evidence from high-quality, large-scale randomized controlled studies.
Most of the current experience in the management of pulmonary embolism in pregnancy is based on the results of studies in nonpregnant patients.
(i) Anticoagulation therapy
The timing of initiation of anticoagulation therapy depends on several aspects: clinical assessment of the diagnostic likelihood of pulmonary embolism, when diagnostic testing can be completed, the severity of the condition, and the risk of bleeding. Clinicians should make a timely assessment of the likelihood of pulmonary embolism before imaging findings are completed.
(ii) Thrombolysis and embolization therapy
In the event of a large pulmonary embolism, pregnant women tend to become hemodynamically unstable very quickly, when a single anticoagulant therapy is usually ineffective. In non-pregnant patients, the most rapid and effective approach is thrombolytic therapy. Thrombolytic drugs include streptokinase, urokinase, and tissue-type fibrinogen activator. Streptokinase does not cross the placenta and is the commonly used thrombolytic agent. Due to the unique nature of pregnancy, the potentially fatal maternal-fetal effects of severe bleeding due to thrombolysis need to be weighed before deciding on thrombolytic therapy. The chance of bleeding in patients receiving thrombolytic therapy for pulmonary embolism in pregnancy is approximately 8%, with the vast majority being genital tract bleeding. Therefore, the decision to thrombolyze must be made only if the expected benefits outweigh the predicted risks.