Review ArticleDiagnosis of deep vein thrombosis and pulmonary embolism in pregnancy
Introduction
Venous thromboembolism (VTE) is one disease with two manifestations: pulmonary embolism (PE) and deep venous thrombosis (DVT). PE is often accompanied by, or preceded by, the development of DVT [1]. PE is a major cause of maternal morbidity and mortality [2], [3], [4], [5], [6] with an overall incidence of 0.5 to 1 per 1000 pregnancies [7], [8]; this represents a three- to fourfold increase in the risk compared with age-matched nonpregnant women [7], [9], [10]. Because missing the diagnosis of VTE has the potential to result in fatal PE [11], and the misdiagnosis of VTE subjects the pregnant woman to an unnecessary risk of anticoagulation, accurate diagnosis of both PE and DVT during pregnancy is important.
The diagnosis of DVT or PE on clinical grounds alone is unreliable [12], and requires an initial high index of suspicion, followed by objective testing of symptomatic patients [13], [14], [15]. Unlike the nonpregnant population where an abundance of safe and accurate algorithms are available, there are no well-designed large clinical studies evaluating the accuracy of objective tests for the diagnosis of DVT or PE in pregnant patients. There are problems with diagnostic testing for DVT and PE during pregnancy. (1) Both clinicians and expectant mothers are reluctant to expose the fetus to ionizing radiation, from tests such as contrast venography (reference standard for DVT), pulmonary angiography (reference standard for PE) and ventilation-perfusion scanning (pivotal test for PE) and (2) physiologic and anatomic changes in the veins of the lower extremities during pregnancy may alter the diagnostic accuracy of objective investigations for DVT. These problems are amplified by the fact that nonthrombotic causes of symptoms such as leg swelling and shortness of breath [16], which mimic DVT or PE, are common during pregnancy, reducing the specificity of symptoms and lowering the prevalence of DVT and PE in symptomatic pregnant patients.
Therefore, recommendations for the diagnosis of DVT or PE during pregnancy are largely empirical and based on extrapolations from studies performed in nonpregnant patients. Large well-designed studies evaluating safe and accurate diagnostic strategies for VTE during pregnancy are still urgently needed because of the potential adverse outcomes, which could result from misdiagnosis.
Section snippets
Pathophysiology of VTE in pregnancy
During pregnancy, physiological changes occur in the coagulation system, which have the potential to result in a net prothrombotic state [17], [18], [19], [20], [21]. There are increased levels of coagulation factors, such as fibrinogen and factor VIII [20], and decreased levels of coagulation inhibitors, such as protein S [21]. These changes occur throughout pregnancy and persist for up to 6 weeks postpartum [18].
In addition to changes in the coagulation system, physiological alterations
Clinical pretest probability
The diagnosis of DVT begins with initial clinical assessment, followed by objective diagnostic testing. Suspicion of DVT is triggered when a patient presents with a swollen leg, associated with calf pain. The pretest probability of a DVT is further increased if associated risk factors are present such as a previous history of VTE, recent surgery or trauma or prolonged immobilization (>3 days), and malignancy [29], [30]. In nonpregnant patients, evaluation of pretest probability (PTP) (either
Diagnosis of PE
The ventilation-perfusion (VQ) scan [14], [15] remains the cornerstone for the diagnosis of PE. Patients who present with suspected PE and undergo VQ scanning can be classified into one of three categories: normal (no perfusion defects in all views), high probability (a segmental or greater perfusion defect with normal ventilation), or nondiagnostic (one or more perfusion defects associated with a corresponding ventilation deficit, or a subsegmental ventilation-perfusion defect) [14]. Because
Diagnosis of PE in pregnancy
Symptoms, which are suspicious of PE, such as dyspnea, tachycardia, and chest pain, occur frequently during pregnancy [16]. Deciding if these symptoms represent the presence of PE may be difficult. Because missing the diagnosis of PE carries significant maternal mortality [2], [3], [4], [5], [6], the threshold for initiating investigation for suspected PE should be low. On the other hand, performing investigations for PE would mean subjecting the developing fetus to ionizing radiation; this can
Conclusions
The accurate diagnosis of VTE in pregnant women, like in the general population, requires initial suspicion, followed by objective testing. However, many of the studies evaluating the role of D-dimer testing and clinical pretest assessment models for the diagnosis of VTE have not included pregnant women.
Because accurate diagnosis of VTE in pregnant women is important to reduce maternal morbidity and mortality, prospective studies investigating safe and accurate approaches to DVT and PE
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JSG is a recipient of a Career Investigator Award from the Heart and Stroke Foundation of Ontario and a Research Chair from the Canadian Institute of Health Research-AstraZeneca.