Venous Thromboembolism in Pregnancy

Abstract

Venous thromboembolism (VTE) is the leading nonobstetric cause of mater nal morbidity and mortality. The risk for deep venous thrombosis (DVT) commences in the first trimester with a striking proclivity for the left lower extremity. Pulmonary em bolism (PE) is more frequent in the postpartum period. Activated protein-C resistance in creases the risk of VTE 30-to 50-fold in heterozygotes and several hundred-fold in homozygotes. Other inherited and acquired factors also increase the risk.The diagnosis of DVT and PE is even more difficult in pregnancy because of the com mon occurrence of leg edema, leg pain, and dyspnea. VTE requires objective proof: (1) DVT-positive duplex ultrasound or impedance plethysmography and (2) PE-positive non invasive lower extremity study, a high-probability perfusion lung scan (normal excludes PE), or a pulmonary angiogram. Concern over fetal radiation from these diagnostic stud ies is not warranted. Initial treatment of VTE is the same as in the nonpregnant patient. However, warfarin should not be used. In its place, low-molecular-weight heparin or unfractionated heparin should be given for the duration of pregnancy; warfarin should be given for at least 6 weeks postpartum or for ≥3 months. The indications for VTE prophy laxis are discussed. Key Words: deep venous thrombosis, embolism, pulmonary embolism, heparinMaternal mortality during and immediately fol lowing pregnancy, labor, and delivery is, fortunately, quite rare. Venous thromboembolism (VTE) is a leading cause of illness during pregnancy and the purperium and is the leading cause of nonobstetric maternal mortality. 1-4 Much of the data available on VTE until very recently has been flawed by lack of ob jective studies for diagnosis and the absence of pro spective randomized trials concerning management. PATHOPHYSIOLOGYVTE is approximately five times greater in pregnant than nonpregnant women of similar age. The most constant predisposing factor is increased venous stasis. The physiologic changes of pregnancy result in increased venous distensability and capaci tance, which are evident in the first trimester. 56 In the second and third trimesters the gravid uterus causes additional venous stasis. Obstetrical factors that independently contribute to the risk of VTE are cesarean section, advanced maternal age, pro longed bedrest, hemorrhage, sepsis, multiparity, and obesity. Coagulation factors II, VII, and X in crease appreciably by midpregnancy. Fibrin genera tion increases and protein-S decreases. Protein-C levels are unchanged. The fibrinolytic system is in hibited, particularly in the third trimester. 7-12 PREDISPOSING FACTORS INHERITEDActivated protein-C resistance (APCR) is due, in a majority of patients, to a specific point mutation in the gene for coagulation factor V-Leiden in which adenine is substituted for guanine at nucleotide 1691. Although only identified recently, it has al ready been shown to be the most common inherited risk factor for VTE.

Venous Thromboembolism: Past, Present and Future

“…There is an increased risk of DVT throughout pregnancy and of PE in the peripartum period. 30 Travel extending beyond 4 hours is also a risk factor (the "economy class syndrome"). 31 Over the last decade, our knowledge of the importance of inherited risk factors has increased dramatically.…”

“…[37][38][39] The antiphospholipid antibodies associated with the lupus anticoagulant (anticardiolipid antibody syndrome) and ovarian stimulation for in vitro fertilization are acquired risk factors. 30,[40][41][42][43][44][45] The clinical findings of PE are extremely sensitive but extremely non-specific. In PIOPED, only dyspnea, tachypnea, chest pain, and crackles were found in more than half the patients with PE.…”

“…If the patient has clinical evidence of DVT or is pregnant, the noninvasive study should be obtained first. 30 These recommendations are based on large randomized prospective consistent multicenter studies utilizing objective validation criteria-so-called level 1 (grade A) evidence. Patients who are unstable should go directly to pulmonary angiography.…”

“…LMWH is also the preferred agent throughout pregnancy. 30 UFH given either intravenously or SC is also effective. It requires frequent monitoring of the anticoagulant effect and prompt dose adjustments.…”

“…An algorithm for the diagnosis of PE using ventilation/perfusion scanning as the initial imaging study. Adapted from Weg 30. …”