Since Wells Clinical Prediction Rule is somewhat not that objective, more objective regulations are further established in recent years, such as Geneva, Charlotte and Miniati rules, which contribute to a more effective and simpler diagnosis of PE for clinicians. The diagnosis is established on the clinical symptoms resulting from Haemodynamic stability or Clinical probability assessment instability (14) (Figure 1).

D-dimer is a soluble degradation production generated from cross linked fibrin based on the fibrinolytic system, with negative prediction value higher than positive prediction value (1). Surgery, tumor, pregnancy, hospitalization and advanced age might result in the elevated D-dimer (18). The quantitative enzyme-linked immunoabsorbent assay (ELISA) showed that the thromboembolic risk was 0.14% in patients with a normal D-dimer concentration within 3 months of not taking anticoagulation therapy (19). Therefore, the positive D-dimer is of little significance in diagnosis of PE after pulmonary lobectomy, while the negative D-dimer plays an important role in acute PE exclusion hence no need of further workups for PE diagnosis. Of course, the blood test be useful as first level exam, especially for low/medium probability of clinical testing of patients is of great significance.

Been widely used in clinic, the chest multi slice CT pulmonary angiography (SCTPA) shows direct signs of pulmonary arterial low-density filling defect, partly or completely surrounded by the opaque blood flow or total filling defect with the distal end of blood vessel being absent. The SCTPA has advantages such as specificity of high spatial/temporal resolution and arterial opaqueness, non-invasiveness, convenience and rapid result acquisition. A large prospective research demonstrated that the sensitivity of SCTPA was 83%, specificity was 95% (20) and sensitivity to the emboli in pulmonary artery was 97% (21). Meanwhile, SCTPA displays abnormalities such as lung infection, pulmonary atelectasis, pneumonedema and pleural effusion, and assists making differential diagnosis of PE. So that in clinical practice, SCTPA has been a preferred method for pulmonary angiography in patients with suspicious PE. The combined pulmonary CT angiography and CT venography of lower extremity improves sensitivity and specificity (83%-90%, 95%-97%, respectively) (20), however, it should be avoided due to its little clinical significance and high dose of radiation (22). Dual-source CT (DSCT), first used in 2006, is fast, accurate and safe in diagnosing PE. DSCT enjoys a higher time resolution, better spatial resolution and less radiation quantity compared with single-source CT (SSCT) (2), and it is still developing along with new technology and improved capacity (23). False negative values by CT in PE patients with high clinical PE probability are reported, however this situation is rare and these patients have small risk of venous thrombosis within 3 months after lobectomy. At present, it is still controversial on whether to perform further examinations and on perform what kind of examination on these patients (1).

Pulmonary ventilation--perfusion scanning remains an effective way for diagnosing patients with contraindications of CT examination such as allergic to contrast agents, with renal failure or pregnancy, in severe conditions or child-bearing age. PE is excluded if pulmonary perfusion defects distributed in lung segments do not match the ventilation imaging, and the normal negative predictive value of ventilation-perfusion scanning is 97% (24). Nevertheless, the ventilation-perfusion scanning is only applicable in diagnosis of 30%-50% suspicious PE patients. A randomized contrastive study of CT and ventilation-perfusion scanning showed that the occurrence rates of VTE were 0.4% and 1.0% in patients excluded from PE by examinations within 3 months, respectively (25). Meanwhile, many diseases affect both ventilation and blood flow, thus the ventilation-perfusion scanning has to be interpreted according to the clinical status. At present, the ventilation- perfusion scanning is only used in patients with renal failure or allergy to contrast medium and pregnant women.

Echocardiography allows bedside operation and is used in evaluation of right ventricular function, which has 96% of sensitivity and 83% of specificity in diagnosis of PE combining with clinical symptoms and electrocardiogram (ECG). Thrombus in the pulmonary trunk is detected in PE patients with hemodynamic instability by transesophageal ultrasonography (26). Echocardiography is the best option for PE patients at high risk (27), it is mainly used in risk stratification though its significance in diagnosis of non-high risk PE is little, and its negative results may not exclude the possiblity of PE.

Since 90% of PE are caused by deep vein thrombosis (DVT) of lower extremities, ultrasonography on the lower extremity has replaced venography in diagnosis of deep venous thrombosis to a great extent. Based on proximal deep venous thrombosis, if the sensitivity is over 90% and the specificity is about 95%, 10% patients would not need for further lung scanning.

Magnetic resonance angiography (MRA) refers to a novel diagnostic technique that can be used in patients with contraindications of iodine contrast agent or ionizing radiation. A prospective Phase III study (29) showed sensitivity and specificity of being 78% and 99% respectively when excluding technique improper (25%). The sensitivity can be increased to 92% in combination with magnetic resonance venography (MRV), whereas the proportion of improper technique also increases to 52%. Compared with SCTPA, MRA takes a longer time, poorer acceptability for patients, also it fails in excluding other cardiovascular and lung diseases apart from PE, besides it is not available for patients with implanted pacemaker and other equipments. MRA is complex, so MRA is only suggested in patients with contraindications to standard workups in conventional medical centers.

The catheter pulmonary angiography is the gold standard in diagnosing PE, with sensitivity at 98% and specificity at 95%-98%. The direct signs are the pulmonary filling defects or complete obstruction of pulmonary artery branches, according to which, small thrombosis of 1-2 mm in length are visible in segmental pulmonary artery (30). Nevertheless, the catheter pulmonary angiography is usually used before skin embolus resection since it is invasive and expensive, and it might lead to complications such as increased local bleeding associated with thrombolytic therapy (TT) and even death in severe patients.

Hypoxia and hypocapnia are common in PE patients, among whom most are with moderate hypoxia. Hypoxemia can be corrected usually by oxygen inhalation through nasal catheter but seldom mechanical ventilation. If mechanical ventilation is required, particular attention are paid to avoid the side effects of hemodynamics, especially in those with high risk PE because mechanical ventilation-induced intrathoracic positive-pressure may decrease venous reflux and progress RV failure (RVF). The acute RVF and the RVF-induced low cardiac output are the main cause for death. Trails show that RVF might be worsened by the strong hyperolemic therapy through excessive stretching of ventricular walls and/or reflex constriction suppression (31). Appropriate liquid infusion may increase the low cardiac indexes and cardiac indexes of PE patients with normal blood pressure (32). Thereby, the appropriate supportive treatment and administration of vasoactive drugs are of great importance to PE patients with RVF.

Strong treatments are necessary for high risk patients, including medication and mechanical thrombolysis. Notably, thrombolysis treatment rapidly resolves thrombus embolism and effectively improves the hemodynamic parameters; furthermore, by thrombolysis treatment performed within 48 hours of the presence of symptoms, the greatest benefit is achievable, and it remains beneficial even to patients with symptoms for 6-14 days (33). immediate thrombolysis treatment is recommended for severe PE patients who are definitely indicated with RVF by echocardiography and thus can not undergo CT examination for confirming diagnosis. Thrombolytic drugs such as streptokinase (SK), urokinase (UK) and rtPA significantly increase the risk of bleeding especially when there are bleeding-related relative risk factors or complications. Since non-invasive imaging technique has been successively used in diagnosing PE in the last decade, the life-threatening bleeding is not common now. Therefore, thrombolysis treatment is performed in all high risk PE patients unless there are absolute contraindications. Pulmonay lobectomy within 3 weeks is a contraindication for thrombolysis, however, all contraindications are comparative since high risk PE patients are encountering immediate life-threatening danger. Molina et al. (34) reported that a 9.6-day interval between the thrombolysis drugs and surgery was relatively safe. Kameyama et al performed thrombolysis treatment in high risk PE patients undergone ineffective anticoagulant treatments, with thrombosis in lobes or lung segments and hemodynamic instability after pulmonay lobectomy (27). Notably, one case was performed 3.5 hours later after surgery and all patients were successfully discharged after active management. The r-tPA thrombolysis with a very short plasma half-life was suggested in such patients because it decreases bleeding.

For patients with absolute contraindications of thrombolysis and unimproved hemodynamic status by thrombolysis, embolectomy is the optimal treatment. Literatures suggested immediate embolectomy after confirming of central PE (35). At present, the indication of pulmonary arterial embolectomy has spread to patients with RVF but without severe shock, with the early mortality rate reported at 6-8% (36). If pulmonary arterial embolectomy also fails to take effect immediately, intraductal embolectomy or repulping surgery of thrombolysis are considered.

Non-high risk PE patients usually have favorable shortterm prognosis. But the mixed data from 6 trials showed no clinical benefits from thrombolysis treatment to this group of patients (37), under this circumstance, anticoagulation therapy should be performed immediately. The rapid anticoagulation is performed only through parenteral anticoagulants such as venous unfractionated heparin (UFH), subcutaneous injection of low-molecular-weight heparin (LMWH) and fondaparinux X a. For patients with high clinical PE probability, anticoagulation therapy is given even before confirming diagnosis (38). Moreover, parenteral anticoagulants usually need to be administered together with the oral vitamin K antagonists (VKAs). A meta analysis showed no significant difference in recurrence rate of VTE, massive hemorrhage and mortality rate between non-high risk PE patients treated with low-molecularweight heparin and those with unfractionated heparin (39). For PE patients with probability of massive hemorrhage or severe renal failure, UFH is suggested as the initial anticoagulation drug, and the partial thromboplastin time (PTT) needs to be detected. Furthermore, the platelet value also needs to be detected due to the risk of heparin-induced thrombocytopenia. For most acute non-high risk PE patients without severe renal failure, LMWH or fondaparinux is a preferred treatment and it’s no need to monitor the dose of subcutaneous injection according to the body weight. No matter UFH, LMWH or fondaparinux, the anticoagulation treatment is supposed for taking at least 5 days. In addition, VKAs are to be used as early as possible and had better combining with anticoagulation treatment. The parenteral anticoagulants are stopped when international normalized ratio (INR) staying at 2.0-3.0 for 2 days. Kilic (40) suggested LMWH for intermediate risk groups so as to avoid complications associated with thrombolytic therapy such as bleeding and secondary pyothorax. Nevertheless, the second urgent thrombolysis is usually required during thrombolytic therapy for intermediate risk patients, though to whom the optimal treatment is still controversial.

A recent systematic review including 11 nonrandomized studies demonstrated that proper outpatient follow-ups allowed effective and safe home treatments in low risk patients. However, it is controversial and the patients should be strictly selected.

There is still no literature definitely on whether thrombolytic therapy is necessary for patients with PE in the single subsegmental lung on SCTPA. At present, thrombolytic therapy is performed merely according to habits of doctors, clinical suspicion and other examinations. Therefore, it is important to study in these patients, whether the risk of fatal PE is greater than that of anticoagulant complications (12).