Symptomatic acute pulmonary embolism (APE) is a major cause of cardiovascular death and morbidity. While there may be clinically asymptomatic subjects, there are also cases resulting in cardiogenic shock and sudden death. The multidetector computed tomography (MDCT) with very thin sections, and low scanning times, has the highest sensitivity and specificity for detecting APE. Computed tomography allows not only detection of the presence of thrombus but also calculation of the pulmonary arterial computed tomographic obstruction index ratio (PACTOIR), which indicates the degree of thrombus in the vascular bed and yields objective results ( 1 ).

PACTOIR and right ventricular dysfunction, which is con-sidered to be one of the prognostic criteria of pulmonary embolism, are correlated ( 1 – 3 ).

Prognostic indicators are also important in APE since they may change the therapeutic approach. Some clinical severity classifications have been made as prognostic indicators in APE ( 4 , 5 ). There are also publications which indicate that biochemical indicators such as troponins, heart-type fatty acid-binding protein, brain natriuretic peptide or N-terminal-proBNP and right ventricular dysfunction may be prognostic factors ( 6 – 10 ). Neutrophil-Lymphocyte Ratio (NLR) is a readily measurable laboratory marker used to evaluate systemic inflammation.Neutrophils are the first elements of inflammation and they play a major role in thrombotic and inflammatory processes ( 11 ). There are studies which demonstrate that NLR, and APE-related mortality development are correlated and that Platelet-Lymphocyte Ratio (PLR), another inflammatory marker, and the clinical severity classification of APE are also correlated ( 12 , 13 ).

In this study, we investigated the correlation between PACTOIR, which shows vascular thrombus load and is considered a radiological prognostic indicator inAPE,NLR and PLR ratios, which may be laboratory prognostic indicators.

This study has been approved by the Local Ethics Committee of Adnan Menderes University SchoolofMedicine. Computed tomography (CT) scans were examined retrospectively for 240 patients who underwent computed tomographic pulmonary angiography at our hospital's Radiology Unit with the suspicion of pulmonary embolism between January 2014 and March 2016. 118 patients were excluded since they had no vascular filling defect which could be APE, 5 patients were excluded due to poor image quality and 22 patients were excluded due to findings consistent with chronic pulmonary embolism. APE was detected in 95 patients by computed tomographic pulmonary angiography. 18 patients were excluded due to malignancy, 10 patients were excluded due to infectious diseases and 5 patients were excluded due to chronic liver disease. As a result, the study was completed with 62 patients who were diagnosed with APE based on computed tomographic pulmonary angiography and started to receive treatment.

Pulmonary CT angiography was performed with a 64-detector MDCT device (Prime Aqu-ilion, Toshiba Medical Systems, Otawara, Ja-pan). Imaging parameters for pulmonary CT angiography were set as 100 kV, 300 mA, 400 ms rotation time, 0.5mm slice thickness, 0.4mm increments,and 64x0.5mm detector collimation (pitch:0.64). In all patients, APE was diagnosed upon the detection of partial or total intraluminal filling defect in the main pulmonary artery and lobar and segmental bronchi.

Computed tomography slice images in the archive system were evaluated by a radiologist with 14 years of experience. In subjects with detected pulmonary embolism, obstruction rate was calculated separately for each patient based on computed tomographic pulmonary angiography.

PACTOIR calculating method; Pulmonary arteries are subdivided into ten segmental arteries in each lung (three to the upper lobe, two to the middle lobe and lingula, five to the lower lobe). The presence of an embolus in a segmental artery is scored as 1 point, and more proximal emboli are scored a value equal to the number of segmental branches arising from the affected vessel. Each score is multiplied by 1 or 2 according to the estimated degree of vascular occlusion (1=partial occlusion; 2=complete occlusion). A subsegmental embolus is considered an embolus in the corresponding segmental artery, with partial occlusion (scoring 1×1=1). Maximum PACTOIR score is 40. The percentage value is then calculated as: (n×d)/40×100 [n=score of embolus multiplied by the number of dependent segments; d=degree of obstruction]. Neutrophil, platelet, lymphocyte, white blood cell (WBC) and D-dimer values were obtained from the hospital's archive system, from laboratory tests made on the same day as the patients' computed tomography scans. At our hospital, peripheral blood samples are collected in calcium-EDTA tubes and blood counts are calculated by auto-analyzer. PLR and NLR were calculated from complete blood counts. Patients included in the study were divided into 2 groups, low PACTOIR group and high PACTOIR group, according to their median PACTOIR values. Neutrophil, platelet, lymphocyte, WBC, NLR, PLR and D-dimer values were compared between the two groups.

Information about the patients' clinical progression was obtained using the hospital's archive system.

A total of 62 patients comprising 25 males and 37 females were included in the study, with a mean age of 62.84±17.75. Patients' median PACTOIR, NLR and PLR values were 23.58% (5-60) ,4.4 (1.3-29.5), 186.5 (45.8-768), respectively (Table-1).

Based on Kendall’s tau-b correlation test, a positive correlation was found between PACTOIR and NLR, PLR, neutrophil and WBC count (p<0.001); and a negative correlation was found between PACTOIR and lymphocyte count (p=0.05) (Table-2).

The low PACTOIR group (PACTOIR ≤23.5) and high PACTOIR group (PACTOIR >23.5) identified according to median PACTOIR levels were compared for complete blood parameters by Mann-Whitney U test, a statistically significant difference was found between the two groups in WBC, neutrophil, NLR, PLR and D- Dimer levels (p<0.05)(Table-3).

Of the patients included in the study, 5 died of acute pulmonary embolism within 1 month following diagnosis. These patients' median PACTOIR, NLR and PLR values were 38% (25- 45), 14.57 (3.11-26.32), 394.2 (104-768), respectively. Statistical analysis wasn't performed because of small number of died patients. However, all patients who died were in the high PACTOIR group.

APEis the third disease of vascular origin that causes the most deaths after coronary artery disease and stroke ( 14 , 15 ). Following the development of multi-dedector CT systems, CT pulmonary angiography (CTPA) became the preferred imaging system in the diagnosis of APE. The most important features of CTPA include its ability to show embolism with a fast and non-invasive technique and to offer alternative diagnoses ( 16 ). Improvement of multi-dedector CT devices allowed high spatial and temporal resolution. Moreover, with increased arterial opacification quality, both sensitivity and specificity values of CTPA increased, making it the first-line imaging method ( 17 – 20 ). CTPA allows not only detection of presence of thrombus but also calculation of the pulmonary arterial computed tomographic obstruction index ratio (PACTOIR), which indicates the degree of thrombus and yieldsobjective results ( 1 ). Severity of thrombosis is determined by using PACTOIR, calculated with the degree of occlusion in the artery and the number of segmental arteries distal to thrombosis. Identifi-cation of PACTOIR allows objective evaluation in subjects with APE.

Determining this index also gives an idea about prognosis in patients with APE and may help to shape the treatment plan. In a study investigating clinical course in patients with APE whose PACTOIR values were calculated, it was noted that 83% of patients witha PACTOIR of more than 60% died while 98% of patients with a PACTOIR of less than 60% recovered with treatment ( 2 ). In our study, the highest PACTOIR level was 60%. 5/62 patients included in study died of APE. Average PACTOIR value was 38% (25-45) for the patients who died versus 25.5% for all patients in the study. Aggressive treatments such as endarterectomy and thrombolytic therapy are recommended in hemodynamically unstable subjects with APE. However, the treatment to be administered for hemodynamically stable subjects with right ventricular dysfunction has not been clearly identified. Therefore, clinical and laboratory predictive factors can be used for such cases. Risk classifications have been made for the early mortality risk in APE ( 4 , 5 ). Similarly, some biochemical indicators (troponins, heart-type fatty acid-binding protein, BNP or N-terminal-proBNP), right ventricular dysfunction determined by echocardiography and right ventricular extension determined by computed tomography are significant for mortality risk ( 6 – 10 ). There are studies that show that myeloperoxidase enzymes and reactive oxygen species (ROS) were elevated in subjects with APE and that the IL-6 level and mortality are correlated in APE ( 21 , 22 ). These findings support that endothelial damage and inflammation play a role in APE. Afzal et al. ( 23 ) reported that WBC count was increased in APE. It was noted that WBC count was more a prognostic indicator than a diagnostic tool ( 24 ). In recent years, it has been claimed that NLR is a better indicator than WBC in indicating inflammation. Neutrophils are the first elements of inflammation and they play a major role in thrombotic and inflammatory processes. It has been suggested that increased NLR in inflammation might be related to the increased level of steroids in relation to stress and increased apoptosis ( 11 ). Kayrak et al. ( 12 ) noted that NLR might have prognostic value in APE. Platelet activation and chemokine secretion also plays an important role in APE. There are studies which provide information as to PLR and aggregation and inflammatory process in thromboembolic events ( 13 , 25 ). Kundi et al. ( 13 ) demonstrated that PLR and a simplified version of pulmonary embolism severity index (sPESI) and mortality were correlated in APE. In this study, we found that PACTOIR values, which indicate the vascular thrombus load and are considered a potential radiological prognostic indicator in APE, are positively correlated with NLR, PLR, neutrophil and WBC counts which may be laboratory prognostic indicators and negatively correlated with lymphocyte counts. Comparison of low PACTOIR and high PACTOIR groups revealed a statistically significant difference between NLR, PLR, Neutrophil and WBC counts. Kayrak et al. ( 12 ) identified an NLR value of 9.2 as cut-off value for death and reported the hazard ratio for this value to be 3.6. In a similar study, it was reported that the mortality rate increased 10.8 times when the NLR cut-off value for death was taken as 5.7 ( 26 ). In our study, average NLR was found to be 9.81±6.96 in the high PACTOIR group with a high thrombus load versus 4.1±2.59 in the low PACTOIR group. A significant difference was found between the NLR values of both groups. In the study on PLR levels, Kundi et al. ( 13 ) reported that a cut-off value of 149 for PLR was significant for high sPESI scores and that mortality rates were statistically higher beyond this value. In our study, average PLR was foundto be 271±157 in the high PACTOIR group versus 171±86 in low PACTOIR group. These results suggest that NLR and PLR values are correlated with PACTOIR, which indicates the thrombus load in the vascular bed.

Limitations of our study include the fact that it is retrospective; the number of patients is small; there are no patients with a PACTOIR value of more than 60%;, information is not available on other inflammatory markers such as C reactive protein (CRP), fibrinogen and myeloperoxidase; and there are no follow-up NLR and PLR values.

In conclusion, NLR and PLR ratios may give an idea about the thrombus load in patients with clinically suspected APE. Also, outcome of patients with APE could estimated according to these parameters.