Case-Based Review

Thrombosis in Pregnancy




Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading nonobstetric cause of maternal death in the United States and in developed countries. 1,2 During pregnancy, the risk for VTE increases four- to six-fold, and although the risk is present throughout pregnancy, the mother is at highest risk immediately postpartum. 3–5

VTE risk is increased due to physiologic and anatomic changes that occur in pregnancy. These changes include hypercoagulability, progesterone-induced venous stasis, decreased venous outflow, compression of the inferior vena cava and pelvic veins by the expanding uterus, and decreased mobility. The hypercoagulability of pregnancy is due to increased levels of coagulation factors I (fibrinogen), VII, VIII, and X, and von Willebrand factor; decreased free protein S, a natural anticoagulant; acquired resistance to activated protein C; and decreased fibrinolysis due to increased levels of plasminogen activator inhibitor-1 and -2. 6,7 These changes confer increased hemostasis to the mother for delivery but also place her at higher risk for thrombosis.

A review of the literature found that more than 70% of pregnancy-associated DVTs are located in the ileofemoral region, as compared with approximately 9% in non-pregnant patients. 8 The proximal location is associated with a higher risk for post-thrombotic syndrome and embolization as compared with calf DVTs. 9 Proximal postnatal thrombosis, smoking, and older age are independent predictors of the development of post-thrombotic syndrome. 10


Clinical risk factors that increase the risk for VTE during pregnancy include a prior history of estrogen-related or unprovoked VTE, being a carrier of severe inherited thrombophilia (homozygotes for factor V Leiden or factor II G20210A variants, double heterozygotes, or persons with antithrombin, protein C, or protein S deficiencies), and the presence of antiphospholipid (aPL) antibodies. 11 Women with systemic lupus erythematosus, diabetes, sickle cell disease, and heart disease also have a high risk for VTE during pregnancy. 12 Other risk factors predisposing to thrombosis include black ethnicity, smoking, operative procedures, conception after assisted reproductive techniques, high body mass index, antepartum immobilization, severe preeclampsia, advanced age and parity, and a family history of VTE. 13 A prospective cohort study of 1,297,037 pregnancies and related puerperium identified the following risk factors for thrombosis: hospitalization, infection, hyperemesis, multiple pregnancies, preeclampsia, obesity, cesarean section, major postpartum hemorrhage, intrauterine growth restriction, and fetal death. 14 Risk factors identified in an Agency for Healthcare Research and Quality study include: age 35 or older, black ethnicity, lupus, sickle cell disease, heart disease, postpartum infection, and transfusion. 15 The combination of more than one risk factor increases the risk for VTE. All these factors have to be considered when deciding on prophylactic or therapeutic anticoagulation therapy in pregnancy. In addition, the risks of anticoagulation, including bruising, bleeding, and other side effects (eg, reduced bone mineral density with therapeutic-dose unfractionated heparin), allergic reactions, and rarely thrombocytopenia, must be considered.



A 31-year-old woman G1P0 at 10 weeks’ gestation with no personal or family history of thrombosis presents with acute onset of shortness of breath and left-sided chest pain that awoke her the morning of presentation. Her vital signs are significant for a heart rate of 106 beats/min, respiration rate of 22 breaths/min, blood pressure of 105/76 mm Hg, and pulse oximetry of 98% on room air. The patient denies previous exposure to oral contraceptives. She does not smoke. She reports that she had noticed left calf pain and swelling, which worsened with walking after a 4-hour drive 2 days prior.

  • What is the approach to diagnosis of thromboembolism in pregnant patients?


Although a clinical diagnosis of DVT in pregnancy is unreliable, a history and physical examination are necessary to exclude other diagnoses and to assess the likelihood of thrombosis. Unfortunately, studies of the accuracy of history and physical examination for detecting DVT and PE have not included pregnant patients. In most pregnant patients with clinically suspected DVT, the diagnosis is not confirmed. Other causes of leg pain and swelling are not uncommon during pregnancy and include cellulitis, ruptured Baker’s cyst, or muscular pain.

A cross-sectional study described the derivation of the LEFt clinical decision rule, which relies on 3 variables in pregnant women with suspected DVT: left leg presentation (L), ≥ 2 cm calf circumference difference (E for edema), and first trimester presentation (Ft). If none of these variables is present, the negative predictive value is 100%. 16 A validation study suggested that a negative LEFt rule accurately identifies pregnant women in whom the risk for confirmed DVT


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