Fibrinogen/Albumin Ratio in Patients with Pulmonary Embolism

Objective: Pulmonary embolism is associated with a high mortality rate when it is not diagnosed emergently. Our aim was to investigate the relationship between the fibrinogen/albumin ratio and pulmonary embolism. Material and Method: Patients who were suspected to have pulmonary embolism and who underwent routine blood testing to initiate the diagnostic process were included in this prospective study. Their fibrinogen and albumin values were evaluated. Results: A total of 130 patients were included in the study. Pulmonary embolism was detected in 71 (54%) of the patients. Of those, 7 (9.9%) were subsegmental, 50 (70.4%) were segmental, and 14 (19.7%) were massive pulmonary. The fibrinogen/albumin ratio of the subjects in the control group was 99.1 (75.2–167.9), whereas the fibrinogen/albumin ratio in the pulmonary embolism group was 151 (125.1–220.5), significantly higher than the control value (P < 0.001). When ROC analysis was performed in the pulmonary embolism group, the fibrinogen/ albumin ratio was found to be a significant predictive factor (AUC: 0.724; 95% CI = 0.635–0.814; P < 0.001). When the fibrinogen/albumin ratio was 119.3, the sensitivity was 77.5%, and specificity was 61.0%. Conclusion: Fibrinogen levels and fibrinogen


INTRODUCTION
Pulmonary embolism (PE) is a general problem of deep vein thrombosis (1).Generally, part of the thrombus from the leg clogs the main pulmonary arteries or smaller pulmonary arteries (2).PE is associated with a high mortality rate when it is not diagnosed emergently.Treatment should be started immediately upon diagnosis.Differential diagnosis includes myocardial infarction, pneumonia, pericardial effusion, and aortic dissection (3,4).Fibrinogen is a plasma protein synthesized in the liver that converts into fibrin during coagulation.It increases in infections, tissue damage, pregnancy, collagen tissue diseases, and many cancers.Fibrinogen levels are decreased in cases of haemolytic diseases, severe blood loss, phosphorus poisoning, disseminated intravascular coagulation, blood transfusion, and burns.The main function of fibrinogen is to provide coagulation (5).Albumin, another protein synthesized in the liver, has a half-life of 21 days.It maintains osmotic pressure with its colloid structure.Serum albumin levels decrease in cases of liver diseases (cirrhosis), kidney diseases (renal excretion), malnutrition, burns, and infections (especially sepsis).It is a negative acute phase reactant (6).This study was aimed to figure out the differences in fibrinogen, albumin, and the fibrinogen/albumin ratio (FAR) values between patients with and without PE, to identify a potential diagnostic marker to assist emergency physicians with diagnosis and decrease unnecessary pulmonary computed tomography angiography.

MATERIAL AND METHODS
The study was approved by Ethical Board (Meeting Decision No. 2018/1434).This prospective study was conducted with patients who were admitted to our university hospital emergency department with the suspicion of PE between July 1, 2018 and February 1, 2019.Patients with suspected pulmonary embolism who were consulted with chest diseases and had computed tomography pulmonary angiography (CTPA) were included in the study.One hundred thirty patients demographic data were collected.The age, gender, biochemistry, arterial blood gas, haemogram test results, and coagulation results of the patients were recorded.Patients who were under the age of 18 were excluded from the study.

Biochemical Markers
Coagulation tubes were centrifuged at 4000 rpm for 5 min.Fibrinogen was measured using a Siemens BCS XP haemostasis system (Siemens Healthcare Diagnostics, Los Angeles, CA, USA).Albumin was measured spectrophotometrically using an Abbott Architect Plus spectrophotometer (Abbott Park, IL, USA).Haemogram was analyzed using automatic blood counter (Beckman-Coulter Co, Miami, Florida).Statistics Categorical variables were defined as the mean ± standard deviation or frequency and percentage.Student's t-test was used to compare normally distributed variables.Normal distribution was evaluated with the Kolmogorov-Smirnov test (P < 0.05).Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic sensitivity and specificity of the FAR.Groups with non-normal distribution were evaluated using the Mann-Whitney U test.A P-value < 0.05 was considered significant.

RESULTS
The data of a total of 130 patients who were suitable for the working conditions were examined.The patients who evaluated within the scope of the study, 71 were included in the study group (PE), and 59 were placed in the control group (no PE).The mean ages of the PE group and the control group were 68.  1.
The albumin values of the subjects in the control group were 3.2 ± 0.7 g/dL, and the albumin values of the patients in the PE group were 3.1 ± 0.6 g/dL.In the statistical evaluation between the groups, no significant difference was found in terms of albumin levels (P = 0.302).Fibrinogen levels were significantly higher in the PE group (520.6 ± 191 mg/dL) than in the control group (379.5 ± 187.6 mg/dL; P < 0.001).The FAR of the subjects in the control group was 99.1 (75.2-167.9),whereas the FAR in the PE group was 151 (125.1-220.5),significantly higher than the control value (P < 0.001).When ROC analysis was performed in the PE group, the FAR was found to be a significant predictive factor (AUC: 0.724; 95% CI = 0.635-0.814;P < 0.001).When the FAR was 119.3, the sensitivity was 77.5%, and specificity was 61.0% (Figure 1).Twenty-seven patients (38%) were followed-up in the service and Forty-four patients (62%) were placed in the intensive care unit (ICU).Nine patients died in the first 3 days of treatment, 11 patients died within 7 days, and 14 patients died within 30 days.Six patients were referred to a different hospital because there was no intensive care unit, and their outcomes are unknown.Mortality rate with known outcomes in the PE group was 21%.et al., fibrinogen levels and FAR were evaluated in 68 patients with ST-elevation myocardial infarction (STEMI).Significantly higher fibrinogen and FAR were detected in STEMI patients (11).In a study by Demir et al, the FAR was significantly higher in the patient group whose Syntax Score was moderatehigh compared to the group with low Syntax Score (12).In a study Kuyumcu et al., the FAR levels were significantly lower in normal ascending aortic diameter group compared with ascending aortic aneurysm group (p<0.001)(13).

DISCUSSION
Qiaodong et al. evaluated the FAR in 151 hepatocellular carcinoma patients.Patients underwent liver resection and were followed to evaluate survival.Patients with a high FAR had poorer survival and a higher recurrence rate (14).In a study conducted by Sun et al., the FAR was compared between 455 control patients and 455 patients newly diagnosed with colorectal cancer.The FAR was significantly higher in patients with colorectal cancer (15).In a study by Wei-Ming et al., 160 patients with rheumatoid arthritis and 159 control patients were enrolled.The FAR was compared between groups, and was found to be significantly higher in rheumatoid arthritis patients (16).
In terms of fibrinogen levels, when patients with and without PE were evaluated, a significant difference (P < 0.001) and a significant difference in FAR (P < 0.001) were found.No statistical correlation was found between the size of PE and FAR.

CONCLUSION
The FAR can be helpful in the diagnosis of PE.Based on the FAR value, physicians may recommend treatment for PE or referral to an ICU.