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The role of thromboelastogram (TEG) and routine coagulation indexes in evaluating the severity of acute pancreatitis in the early stage of onset
1Department of Critical Care Medicine, The Affiliated Hospital of Zunyi Medical University, 563000 Zunyi, Guizhou, China
*Corresponding Author(s):sandy33619@163.com (Wenmei Liang)
| History | Submitted: 06 September 2022 | Accepted: 01 December 2022 | Published: 08 May 2023 |
| Copyright: | ©2023 The Author(s). Published by MRE Press. |
To study the role of thromboelastogram (TEG) and routine coagulation indexes in evaluating the severity of acute pancreatitis (AP) in the early stage of onset. A total of 123 patients with acute pancreatitis treated at our hospital from January 2018 to January 2021 were divided into three groups according to their disease severity. We analyzed the correlation and prognostic significance of TEG, routine coagulation indexes and blood platelet (PLT) count with disease severity. The clot reaction time (R-value), clot generation time (K-value), maximum width value (MA-value) and clot generation rate (α-angle) between the three groups were significantly different (p < 0.05). The level of prothrombin time (PT), D-dimer (D-D) and fibrinogen (FIB) and PLT count of the mild group were significantly different from the moderate and severe group as well as between the moderate and severe group (p < 0.05). Spearman correlation analysis showed that α-angle, MA-value, PT, D-D, activated partial thromboplastin time (APTT) and FIB were positively correlated, while platelet count, R-value and K-value were negatively correlated with the severity of AP. According to the follow-up results, 110 patients were divided into the survival (n = 95) or the death (n = 15) group. The R- and K-values in the survival group were significantly higher than those in the death group, while the α angle, MA-value, PT, APTT, D-D and FIB in the death group were significantly lower than those in the death group (p < 0.05). The severity and prognosis of patients with AP were directly related to the degree of coagulation disorder, and TEG combined with routine coagulation indexes demonstrated high evaluation significance for determining the severity and prognosis of AP patients.
Cite this article
Wenmei Liang, Tonghua Liu, Minmin Gong. The role of thromboelastogram (TEG) and routine coagulation indexes in evaluating the severity of acute pancreatitis in the early stage of onset. Signa Vitae. 2023; 19(3): 132-136. doi: 10.22514/sv.2023.029
1. Objects and methods
1.1 Basic information
This study was a retrospective review of adult patients with AP who underwent treatment at the Affiliated Hospital of Zunyi Medical University Hospital from January 2018 to January 2021. To assess the severity of AP, the “Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus” was consulted [1]. The diagnostic criteria for AP were as follows: (1) the pancreatitis was characterized by abdominal pain (persistent or radiating to the back); (2) serum amylase or lipase was elevated at least three times the upper limit of normal (ULN); (3) computed tomography (CT), magnetic resonance imaging (MRI) or transabdominal ultrasonography showing typical AP imaging results. At least two of the above three features were required to be present for diagnosing AP.
The study inclusion criteria were: (1) having at least two of the above three diagnostic criteria, (2) the presence of symptoms of acute abdominal pain, fever, nausea and vomiting, and (3) patients or family members provided signed informed consent. The exclusion criteria were: (1) patients with a history of thrombotic and hemorrhagic diseases, (2) the presence of hepatic and renal insufficiency as well as cardiovascular or cerebrovascular diseases, (3) patients with combined immune system, hematological and infectious diseases, (4) end-stage malignant diseases, (5) recent use of non-steroidal anti-inflammatory drugs or anticoagulants, (6) psychiatric diseases or medical history, (7) incomplete clinical data, and (8) poor compliance to treatment.
1.2 TEG and routine coagulation indexes testing
Briefly, 5 mL of fasting venous blood was collected from patients within 12 hours after admission to our hospital. The Haemonetics TEG 5000 Thrombelastograph Analyzer (Haemonetics Corp, Braintree, MA, USA) was used for TEG testing. Each TEG index, including clot reaction time (R-value), clot generation time (K-value), clot generation rate (α-angle) and maximum width value (MA-value), was recorded in detail. For routine coagulation index testing, the levels of prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer (D-D) and plasma fibrinogen (FIB) were investigated using the fully automatic CS2000 Hemagglutination Analyzer (SYSM EX, Kobe, Japan) and matching reagents. Their blood platelet (PLT) count was determined using the MEDONIC CA620 Blood Cell Analyzer (Boule, Domnarvsgatan 4, SE-163 53 Spånga, Sweden).
1.3 Observation indexes
The TEG, routine coagulation indexes and blood PLT count of patients in each group were compared. Then, the correlation between TEG, routine coagulation indexes, blood PLT count and disease severity was analyzed, and their significance on the prognosis of AP patients was evaluated.
1.4 Statistical analysis
The SPSS (v22.0, International Business Machines Corporation, Chicago, IL, USA) statistical software was used for data analysis. Continuous data are described as (n (%)) according to the χ2 test, and measurement data are expressed as x̄ ± s. The t-test was used to compare differences between groups, and analysis of variance (ANOVA) was used to analyze the differences between multiple groups. The correlation between TEG, routine coagulation indexes and disease severity was analyzed using Spearman’s correlation analysis. p < 0.05 was used to indicate statistical differences.
2. Results
2.1 Baseline characteristics of AP patients
A total of 123 AP patients admitted to our hospital from January 2018 to January 2021 were selected and divided into 3 groups: mild (n = 45), moderate (n = 42) and severe (n = 36) according to their disease severity. Our analysis showed that the clinical data of the three groups were homogeneous (p > 0.05) (Table 1).
| Variables | Case | Gender (male/female) | Age (yr) | Body mass index (kg/m2) |
| Mild group | 45 | 25/20 | 54.00 ± 6.21 | 20.50 ± 1.12 |
| Moderate group | 42 | 23/19 | 54.50 ± 6.19 | 20.50 ± 1.10 |
| Severe group | 36 | 20/16 | 54.50 ± 6.17 | 21.00 ± 1.08 |
| F value | 0.005 | 0.093 | 2.623 | |
| p value | 0.940 | 0.911 | 0.077 |
2.2 Comparison of TEG parameters between different groups of patients
Comparative analysis of the R-value, K-value, α-angle and MA-value between the three groups (p < 0.05) showed that patients in the severe group had the lowest R-value and K-value but the highest α-angle and MA-value, while those from the mild group had the highest R-value and K-value but lowest α-angle and MA-value (Table 2).
| Variables | Case | R-value (min) | K-value (min) | Α-angle (°) | MA-value (mm) |
| Mild group | 45 | 6.89 ± 0.78 | 1.99 ± 0.45 | 65.30 ± 5.74 | 66.98 ± 7.02 |
| Moderate group | 42 | 5.10 ± 0.95 | 1.39 ± 0.74 | 69.35 ± 6.85 | 69.47 ± 8.85 |
| Severe group | 36 | 4.32 ± 1.02 | 0.87 ± 0.70 | 72.38 ± 7.54 | 73.99 ± 8.12 |
| F value | 86.062 | 31.387 | 11.468 | 7.755 | |
| p value | 0.000 | 0.000 | 0.000 | 0.001 | |
| R-value: clot reaction time; K-value: clot generation time; A-angle: clot generation rate; MA-value: maximum width value. |
2.3 Comparison of routine coagulation indexes and blood PLT counts between different groups of patients
The levels of PT, APTT, D-D, FIB and PLT counts were also compared between the three groups (p < 0.05). The results revealed that all routine coagulation indexes were highest in the severe group except for PLT count, which was the lowest. Comparatively, opposite results were obtained for the mild group. In addition, the level of APTT in the mild and moderate groups was not statistically significant (p > 0.05), while the levels of PT, D-D, FIB and PLT were significantly different between the two groups (p < 0.05). All indexes compared between the mild and severe group or the moderate and severe group were statistically significant (p < 0.05) (Table 3).
| Variables | Case | PT (s) | APTT (s) | D-D (mg/L) | FIB (g/L) | PLT (×109/L) |
| Mild group | 45 | 13.85 ± 1.14 | 28.92 ± 5.10 | 1.50 ± 0.71 | 2.43 ± 1.08 | 100.20 ± 35.60 |
| Moderate group | 42 | 14.30 ± 1.11 | 30.05 ± 6.62 | 1.78 ± 0.69 | 4.05 ± 1.01 | 78.89 ± 25.33 |
| Severe group | 36 | 16.85 ± 1.20 | 52.30 ± 5.84 | 3.69 ± 0.70 | 5.89 ± 1.05 | 50.10 ± 23.20 |
| F value | 76.502 | 193.058 | 111.351 | 109.138 | 29.864 | |
| p value | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | |
| t mild vs. moderate | 1.863 | 0.895 | 1.863 | 7.213 | 3.196 | |
| p mild vs. moderate | 0.022 | 0.124 | 0.022 | 0.000 | 0.000 | |
| t mild vs. severe | 11.497 | 19.219 | 13.881 | 14.505 | 7.291 | |
| p mild vs. severe | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | |
| t moderate vs. severe | 9.743 | 15.617 | 12.106 | 7.876 | 5.201 | |
| p moderate vs. severe | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | |
| PT: prothrombin time; APTT: activated partial thromboplastin time; D-D: D-dimer; FIB: fibrinogen; PLT: blood platelet. |
2.4 Analysis of the correlation between TEG, routine coagulation indexes and disease severity
Spearman analysis was used to assess the correlation between each index and disease severity. Our results showed that the α-angle, MA-value, PT, APTT and the levels of D-D and FIB were positively correlated with the severity of AP (r = 0.798, 0.813, 0.805, 0.885, 0.815 and 0.820, respectively, p< 0.001). However, PLT counts, R-value and K-value were negatively correlated with AP severity (r = -0.817, -0.824 and -0.830, respectively, p < 0.001) (Table 4).
| Indexes | Severity of AP | |
| r | p value | |
| a-angle | 0.798 | 0.033 |
| MA-value | 0.813 | 0.020 |
| PT | 0.805 | 0.025 |
| APTT | 0.885 | 0.008 |
| D-D | 0.815 | 0.018 |
| FIB | 0.820 | 0.014 |
| PLT | −0.817 | 0.017 |
| R-value | −0.824 | 0.012 |
| K-value | −0.830 | 0.010 |
| AP: acute pancreatitis; α-angle: clot generation rate; MA-value: maximum width value; PT: prothrombin time; APTT: activated partial thromboplastin time; D-D: D-dimer; FIB: fibrinogen; PLT: blood platelet; R-value: clot reaction time; K-value: clot generation time. |
2.5 Association of TEG and routine coagulation indexes with the survival of AP patients
In this study, during the 1-year follow-up visits, 2 patients were lost to follow-up, and 1 died due to other diseases. Thus, a total of 110 patients were successfully followed, demonstrating a follow-up rate of 89.43%. According to the follow-up results, the 110 patients were divided into a survival group (n = 95) or a death group (n = 15). Patients in the survival group had significantly higher R- and K-values but significantly lower α-angle, MA-value, PT, APTT and levels of D-D and FIB than those in the death group (p < 0.05) (Table 5).
| Variables | Case | R-value (min) | K-value (min) | a-angle (°) | MA-value (mm) | PT (s) | APTT (s) | D-D (mg/L) | FIB (g/L) |
| Survival group | 95 | 5.88 ± 1.04 | 1.92 ± 0.56 | 65.88 ± 3.04 | 63.65 ± 8.52 | 12.85 ± 2.59 | 31.89 ± 7.02 | 1.59 ± 0.90 | 3.44 ± 1.35 |
| Death group | 15 | 3.24 ± 0.85 | 1.56 ± 0.81 | 76.08 ± 9.25 | 77.53 ± 8.49 | 16.77 ± 5.52 | 54.10 ± 10.01 | 4.92 ± 0.90 | 6.06 ± 1.40 |
| t value | 9.340 | 2.166 | 8.393 | 5.866 | 4.51 | 10.694 | 13.317 | 6.951 | |
| p value | 0.000 | 0.033 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | |
| R-value: clot reaction time; K-value: clot generation time; α-angle: clot generation rate; MA-value: maximum width value; PT: prothrombin time; APTT: activated partial thromboplastin time; D-D: D-dimer; FIB: fibrinogen. |
2.6 Analysis of the value of TEG and routine coagulation indexes for disease severity and prognosis assessment
Further analysis comparing the R-value, K-value, α-angle, MA-value, PT, APTT, D-D and FIB using individual assays demonstrated higher sensitivity and specificity when the indexes were combined in determining the severity of AP and patients’ prognoses (p < 0.05) (Table 6).
| Indexes | Severity of AP | Prognosis | |||||
| 95% CI | Sensitivity (%) | Specificity (%) | 95% CI | Sensitivity (%) | 95% CI | Specificity (%) | |
| A-angle (°) | 0.733∼0.840 | 74.21 | 68.23 | 0.735∼0.841 | 75.20 | 0.740∼0.812 | 69.20 |
| MA-value (mm) | 0.735∼0.868 | 75.02 | 69.33 | 0.738∼0.852 | 74.66 | 0.745∼0.849 | 70.11 |
| R-value (min) | 0.768∼0.855 | 72.01 | 70.51 | 0.769∼0.856 | 73.36 | 0.773∼0.849 | 71.20 |
| K-value (min) | 0.552∼0.678 | 62.52 | 61.30 | 0.458∼0.632 | 52.52 | 0.439∼0.648 | 60.33 |
| PT (s) | 0.798∼0.886 | 69.62 | 70.20 | 0.754∼0.888 | 69.98 | 0.750∼0.892 | 70.21 |
| APTT (s) | 0.810∼0.932 | 75.65 | 71.20 | 0.818∼0.935 | 76.20 | 0.828∼0.920 | 71.35 |
| D-D (mg/L) | 0.795∼0.889 | 71.21 | 72.20 | 0.854∼0.954 | 74.52 | 0.861∼0.943 | 70.21 |
| FIB (g/L) | 0.820∼0.963 | 76.85 | 70.33 | 0.865∼0.987 | 75.50 | 0.871∼0.979 | 71.54 |
| Combined | 0.885∼0.996 | 91.20 | 88.95 | 0.875∼0.994 | 91.23 | 0.886∼0.988 | 88.86 |
| AP: acute pancreatitis; A-angle: clot generation rate; MA-value: maximum width value; R-value: clot reaction time; K-value: clot generation time; PT: prothrombin time; APTT: activated partial thromboplastin time; D-D: D-dimer; FIB: fibrinogen; CI: Confidence intervals. |
3. Discussion
AP is a relatively common clinical disorder of the digestive system associated with cholelithiasis, biliary infection and pancreatic duct obstruction [2]. It is an inflammatory disease in which pancreatin is activated in the pancreas by multiple etiologies, causing a local or systemic reaction in the pancreatic tissues [3]. In clinics, a greater variation in the status of AP patients is usually observed, as most mild AP patients can be cured after active treatments. However, patients with severe AP often suffer from acute morbidity and rapid disease progression and are highly susceptible to multiple organ failure; thus, they have a mortality rate of up to 30% [4]. Therefore, early assessment of the condition and disease severity are important to provide a reliable basis for developing a targeted treatment strategy and improving patients’ prognoses.
In the early stages of AP, the pancreas releases a large amount of cytokines and inflammatory mediators, which can activate the coagulation pathway and initiate the exogenous and endogenous coagulation pathways, leading to disorders of coagulation function in patients [5]. Previous studies showed that the severity of AP and the development of complications were closely associated with the degree of dysfunction in the coagulation system [6, 7]. PT, APTT, FIB, D-D and other biomarkers can be used as indicators to assess routine coagulation function in clinics to effectively reflect the coagulation function of patients in the initial coagulation stage. APTT and PT have the advantages of no blood cell involvement in the detection process and do not involve the influence of PLT aggregation and adhesion on coagulation function. Comparatively, FIB can reflect the change in quantity but not in its function. D-D is a marker of secondary fibrinolysis, and its alterations in organisms suggest the possible formation of microcirculatory thrombosis secondary to the alteration of fibrinolysis [8, 9]. In this study, we found differences in the levels of PT, APTT, D-D and FIB as well as blood PLT counts between patients with different severity of AP. This finding indicates that a more severe patient condition would result in higher levels of coagulation indicators, thus, urging the need for a timely targeted treatment plan. However, reports have shown that the assessment of the severity and prognosis of AP using coagulation indexes alone could have some clinical limitations [8].
In the thromboelastogram, R-value can effectively reflect the activity of clotting factors, while K-value and α-angle can effectively reflect the rate of clot formation, and MA-value and G-value can reflect the maximum intensity of clot formation [10, 11]. In this present study, the data showed statistical differences in R-values, K-values, α-angle and MA-values between the three groups of patients with different severity of AP. In addition, thromboelastography parameters were significantly different in patients with mild, moderate and severe AP. Previous studies also reported that the coagulation function of AP patients was disordered and directly related to the severity of the disease [12]. Additionally, we hypothesize that the underlying mechanism might be due to significantly higher levels of PLT and fibrinogen in the plasma of patients with severe AP, resulting in stronger and more stable blood clots and a faster clot formation rate [8, 9]. In addition, the results of our study also showed that α-angle, MA-value, PT, APTT, D-D and FIB were positively correlated with AP disease severity (p < 0.001), while PLT, R-value, and K-value were negatively correlated with AP disease severity (p < 0.001). The results also suggested that TEG and routine coagulation indexes have a certain relationship with AP disease severity, which might be important in assessing the severity of a patient’s disease.
The results of this study showed that the R- and K-values of patients in the survival group were significantly higher than those in the death group, while the α-angle and MA-value were significantly lower than those in the death group. The data suggested that the degree of TEG indexes disorders in AP patients significantly correlated with the prognosis of the disease, similar to the study of ChengFan et al. [13].
4. Conclusions
In this study, we found that α-angle, MA-value, PT, APTT, D-D, FIB level and blood PLT counts were positively correlated with AP disease severity, while R-value and K-value were negatively correlated with AP disease severity. Therefore, TEG combined with routine coagulation indexes might be important in assessing AP severity and patients’ prognosis. In the future, we aim to further explore the underlying mechanism of the coagulation system in pancreatitis-associated lung injury.
Availability of Data and Materials
Not applicable.
Author contributions
WL—designed the research study. TL—performed the research and analyzed the data. MG—wrote the manuscript. All authors read and approved the final manuscript.
Ethics approval and consent to participate
Ethical approval was obtained from the Ethics Committee of the Affiliated Hospital of Zunyi Medical University (Approval no. KLL-2022-698). Written informed consent was obtained from a legally authorized representative(s) for anonymized patient information to be published in this article.
Acknowledgment
We thank the peer reviewers for their valuable suggestions.
Funding
This work was supported by Science and Technology Fund Project of Guizhou Provincial Health Commission (Grant No. gzwkj2023-114).
Conflict of interest
The authors declare no conflict of interest.
