Current approach to classify risk factors is considering that venous thromboembolism results from both interaction between patient-related risk factor and setting-related risk factors [9–11] (Table 4.2). The first, are considered to be permanent, whereas the second, temporary. Risk factor evidence including age, past history of deep venous thrombosis, major trauma, lower limb fractures, spinal cord injury, left ventricular dysfunction, cancer, chronic obstructive pulmonary disease, and infection can interact predisposing hospitalization and deep venous thrombosis. Interestingly, the predictive weighs for these factors are unequal and venous thromboembolism could occur in patients without any identifiable predisposing factor [10] in up to 30 % of PE patients. In women, oral contraception use, even in reduced dose of estrogen, represent still an increased risk [12]. Pregnancy and postpartum period are related with venous thromboembolism and is an important cause of maternal morbidity and mortality. The risk is highest by the last trimester of pregnancy and 6 weeks after delivery [12–14]. Due to nonspecific presentation, PE could be a challenging ruling-out disorder. However, a prompt stratification and expedite diagnosis are fundamental to offer an early directed treatment. Being aware of patient’s particular profile together with risk factors could help physician choosing a most appropriate stratification and diagnostic approach.

Current European Cardiology Society guidelines on PE classified the risk factors regarding the odds ratios are as follows: Strong risk factors (odds ratio >10): Fracture of lower limb previous 3 months, hip or knee replacement, major trauma, myocardial infarction (within previous 3 months), previous venous thromboembolism, and spinal cord injury. Moderate risk factors (odds ratio 2–9): arthroscopic knee surgery, auto–immune diseases, blood transfusion, central venous lines, chemotherapy, congestive heart or respiratory failure, erythropoiesis-stimulating agents, hormone replacement therapy (depends on formulation), in vitro fertilization, cancer (highest risk in metastatic disease), oral contraceptive therapy, paralytic stroke, postpartum period, and thrombophilia. Weak risk factors (odds ratio <2): Bed rest >3 days, diabetes mellitus, hypertension, immobility due to sitting (e.g., prolonged car or air travel), increasing age, laparoscopic surgery (e.g., cholecystectomy), obesity, pregnancy, and varicose veins [7]. An interesting observation is that stronger risk factors with odds ratio ranging from <2 to >10 were all involved with inflammation, coagulation cascade, and platelet activation.

From our point of view, risk factors could be classified on molecular bases [15]. A reorganization of the risk factors, taking into account the molecular evidence, is shown in Table 4.3. Inflammation involves several conditions in health and disease related historically with deep venous thrombosis and PE. Secondary thrombophilia includes factors associated with the coagulation cascade and platelet activation to a greater or lesser degree; as well as other mechanisms observed in different clinical situations. Molecular thrombophilia was separated in acquired and hereditary. Finally, independent of the risk factors, stasis or infections are the triggers for acute thromboembolic event.

Different calculation rules have been validated in predicting probability (low, moderate, or high-clinical probability, PE likely or unlikely) (Table 4.4), and adverse outcome [16, 17] (Table 4.5). These scores account both for the clinical severity of an acute event and the patient’s comorbidity. The Pulmonary Embolism Severity Index (PESI) has been widely validated. One of its major strength is ruling out an adverse outcome as evidenced by the high negative predictive value of the classes II and I. On the other hand, a weak of the original PESI score is the many unequally weighed variables that can become a quite multipart calculate, reducing eventually its workability in an emergency setting. A simplified version (sPESI) assesses only six equally weighed variables and accurately identifies patients with PE who are at low risk of death and other complications [18]. Those patients with moderate or high pretest probability should continue their assessment with an imaging modality.

Considering that dyspnea plus near-syncope or syncope or dyspnea associated to ischemic-like chest pain in PE patients has been associated with >50 % of pulmonary arterial obstruction in pulmonary angiography and with severe right ventricular dysfunction, respectively, we considered that both conditions could be added to proposed PSI score, maintaining pulse, systolic blood pressure, respiratory rate, and oxygen saturation. This simple tool could be used in emergency department by physicians with or without experience. Our proposal required clinical validation.

In the stratification approach, this accessible tool provides important findings to identify severe right ventricular pressure overload and ventricular ischemia. An electrocardiogram never will be normal in submassive or massive PE. The traditional right axis deviation is not always present, specifically during the early state of the acute event. In Fig. 4.1 a normal preoperative ECG, then in-hospital patient had a massive PE complicated with patent foramen ovale and paradoxical embolism to right coronary artery. In Fig. 4.2, there is not a right axis deviation expected in massive PE; however there is almost 60° axis deviation compared with the first electrocardiogram; also other electrocardiogram findings described in massive PE are observed; lead standard DI, aVL, chest leads V2, V3, and V4 ST depression, aVR-ST elevation [19] and chest lead V1 with qR and ST elevation: ST elevation in standard inferior leads are secondary to right coronary paradoxical embolism.

In the setting of PE patients, on admission aVR-ST elevation was present in 34.3 % (n = 136). Presence of aVR-ST elevation was associated with more severe clinical presentation (dyspnea at rest 44.9 % vs. 29.2 %; p = 0.002, hypotension 17.0 % vs. 6.5 %; p = 0.001, syncope 16.2 % vs. 6.5 %; p = 0.002), higher median troponin T levels (0.035 [0.01–0.2] vs. 0.01 [0.01–0.02]; p 0.001), more frequent right ventricular dysfunction (74.5 % vs. 46.6 %; p 0.001), and central located thrombi (50.8 vs. 29.2; p 0.001). Thrombolysis was used more frequently (29.1 % vs. 7.5 %; p 0.001) and in-hospital-mortality was increased (10.3 % vs. 5.4 %; p = 0.07) when compared to patients without that sign. Mortality in intermediate-risk PE patients with aVR-ST elevation was 8.9 % compared to 0 % in those without (p = 0.04). In contrast, the presence of other classical electrocardiogram pattern of PE did not further increase mortality in intermediate-risk patients. Finally, ST elevation in lead aVR is associated with a more severe course of PE, especially in patients with intermediate-risk. Therefore, aVR-ST elevation might be useful in risk stratification of PE [20].