Study of the Significance of Thromboelastography Changes in Patients with Dyslipidemia.

Purpose: To investigate the changes in thromboelastography (TEG) in patients with dyslipidemia to study its effect on the blood coagulation status.
Methods: 131 patients hospitalized in Fujian Provincial Jinshan Hospital from January 2018 to December 2020 were selected, and 64 cases in the hyperlipidemia (HL) group and 67 cases in the non-HL group were set according to whether their blood lipids were abnormal. By measuring the changes of each parameter of TEG in patients, the relevant parameters R value, K value, α angle, and MA value were calculated. And routine blood coagulation (PT, APTT, INR, FIB, and TT) and routine blood (platelet count) tests were performed on all study subjects to analyze the changes of each index of the coagulation function and each parameter of TED in both groups and explore the clinical value of TEG on HL diseases.
Results: Compared with the non-HL group, R and K values decreased, and angle and MA values increased in the HL group (P < 0.05). PT, APTT, and INR values decreased, and FIB values increased in the HL group compared with the nonhyperlipidemic group (P < 0.05). The TT levels were similar in the non-HL group and the HL group (P > 0.05). Compared with the non-HL group, PLT values decreased, and PDW and MPV values increased in the HL group (P < 0.05). R value was positively correlated with APTT, r= 0.373, P=0.002. K value was negatively correlated with PLT, r= -0.399, P=0.002. α angle and MA values were positively correlated with PLT, r= 0.319/0.475, P=0.010/P < 0.001. The rest of the indexes did not correlate with each parameter of TEG significant correlation.
Conclusion: TEG can predict the hypercoagulability and hypocoagulability of blood by the changes of R value, K value, α angle, and MA to evaluate the effect of hyperlipidemia on the coagulation status, which is important for guiding the adjustment of lipid-lowering, antithrombotic, and anticoagulation programs in patients with atherosclerosis combined with hyperlipidemia or postsurgery combined with hyperlipidemia.

1. Preface

Dyslipidemia refers to the abnormalities of lipid mass and quality in plasma, which actually manifests as lipoprotein abnormalities, and the process of lipoprotein metabolism is complex [1]. Modern medical disease establishment data [2, 3] show that the number of cardiovascular and cerebrovascular disease deaths caused by hyperlipidemia is about 3600 cases per day worldwide, and the number of cardiovascular and cerebrovascular diseases caused by hyperlipidemia in China is increasing at a rate of 12% per year. In hyperlipidemia (HL), it can damage systemic arterial endothelial cells and lead to their dysfunction, and some studies [4, 5] have confirmed that HL is an independent risk factor for atherosclerosis and coronary heart disease. In addition, HL can also cause systemic or local blood circulation disorders and cause the risk of associated arterial thrombosis, which shows that early detection of dyslipidemia and monitoring its level changes is an important basis for effective implementation of atherosclerotic cardiovascular disease (ASCVD) prevention and treatment measures. Conventional hemagglutination is a part of the overall coagulation process and is a microscopic reflection of some of the coagulation factor activity and is also used to determine coagulation function conventional assays that cannot assess the entire dynamic changes in blood coagulation [6]. In contrast, the thromboelastograph (TEG) has a significant role in real-time monitoring of the time and rate of clot formation, the hardness and stability of clot formation, and objectively evaluating the aggregation function of platelets, which is more prominent in clinical treatment [7, 8]. TEG dynamically reflects the whole process of coagulation cascade reaction by rapidly assessing the physical properties of clots and can detect both the bleeding status and thrombus and prethrombotic status, and it is now widely used in various clinical departments [9]. The parameters of TEG hematocrit clot formation time (K), hematocrit clot formation rate (α-Angle), and maximum clot strength or hardness (MA) have different clinical significance. Based on the changes in the parameters, the changes in the function of the hemostatic, coagulation, and anticoagulation systems of patients with HL can be initially determined, and the coagulation status of patients can be detected to provide a theoretical basis for clinically targeted anticoagulation and antithrombotic treatment [10-12]. The aim of this study was to observe the changes in various parameters of TEG in patients with HL and analyze the relationship between them and their blood coagulation status.

2. Data and Methods

2.1. Study Population and Grouping

131 patients hospitalized in Fujian Provincial Jinshan Hospital from January 2018 to December 2020 were selected for inclusion criteria: patients with proposed hernia surgery, benign thyroid nodules, breast hyperplasia or benign nodules, and who underwent lipid and TEG examinations in the internal medicine clinic; had not taken lipid-lowering drugs within 1 month before enrollment; were older than 20 years; and all patients in the HL group met the diagnostic criteria for hyperlipidemia. Exclusion criteria were hypertension, coronary heart disease, diabetes, stroke, acute or chronic infectious diseases, malignant tumors, autoimmune system diseases, and hematologic diseases; patients with severe hepatic or renal insufficiency; women who were pregnant or planning to become pregnant or lactating; and patients who were judged to be unsuitable for participation in this study. According to the patients' lipid levels, they were divided into 64 cases in the HL group and 67 cases in the non-HL group. There was no statistically significant difference between the two groups in terms of gender ratio and age (all P > 0.05), which could be studied in a controlled manner.

2.2. Data Collection

General information (gender, age), biochemical indices (GLU: glucose, CR: creatinine, UA: uric acid, WBC: white blood cells, RBC: red blood cells, and HB: hemoglobin) and lipid index levels (TG: triglycerides, TC: total cholesterol, HDL-C: high-density lipoprotein cholesterol, and LDL-C: low-density lipoprotein cholesterol) were collected by reviewing the medical records of the two groups. These data were also counted and compared.

2.3. Diagnostic Criteria for HL

Refer to the diagnostic criteria in the “Guidelines for the prevention and treatment of dyslipidemia in Chinese adults” developed by the Chinese Journal of Circulation in 2016 [12], triglycerides (TG) ≥ 1.7 mmol/L and/or total cholesterol (TC) ≥ 5.2 mmol/L.

2.4. Measurement of Coagulation Indexes

The ACLTOP 300CTS fully automated blood coagulation assay analyzer (Beckman, USA) was used for testing. The detection indexes were PT (plasma prothrombin time), TT (prothrombin time), APTT (activated partial thromboplastin time), FIB (fibrinogen), and INR (international normalized ratio).

2.5. Platelet Index Detection

The automatic blood cell morphology analyzer was used for detection. The detection indexes were the blood platelet (PLT), platelet distribution width (PDW), and mean platelet volume (MPV), respectively.

2.6. Determination of TEG Index Testing

TEG-5000 and its original supporting reagents were purchased from HAEMONETICS Corporation, USA. All study subjects collected 2 ml of venous blood in the early morning on an empty stomach, mixed with 3.8% sodium citrate and venous blood 1:9, using the whole blood recalcitrance method; aspirated 1 ml was added to the kaolin cup after 30 min of rewarming at room temperature and mixed slowly 6 times, placed at room temperature for 5 min and then prepared for use, loaded the disposable test cup into the testing rack of the instrument, added calcium chloride to the cup, and then added the above mentioned components slowly according to the proportion. Kaolin samples were added to the cup, and the test was performed according to the corresponding procedure. All specimens were tested within 2 h after blood collection.

2.7. Lipid Determination

All subjects had 5 ml of venous blood drawn, including 3 ml of blood without the added anticoagulant, and serum was collected for the lipid assay after centrifugation at 4000 r/min for 15 min. Serum TC, TG, HDL-C, and LDL-C levels were measured by the Roche cobas c701/702 automatic biochemical analyzer (Roche, Switzerland), TC by the cholesterol oxidase method, TG by the enzyme colorimetric method, and HDL-C and LDL-C by the phase enzyme colorimetric method.

2.8. Statistical Methods

The SPSS 25 software package was used for analysis, the measurement data were expressed as (Mean ± SD), t-test was used to compare the means between the groups, the statistical data were expressed as n (%), and the chi-square test was used for comparison between the groups. Pearson or spearman software was used to analyze the correlation between the parameters of TEG and coagulation indexes, and the difference was statistically significant at P < 0.05.

3. Results

3.1. Comparison of General Conditions

There was no statistically significant difference in age and gender between the non-HL group and the HL group (P > 0.05) (Table 1).

Table 1

General information of patients.

General	HL group (n= 64)	Non-HL group (n= 67)	Statistical quantity	P value
Age (years)	53.06 ± 11.68	50.24 ± 14.26	1.235	0.219
Sex (number of cases) male/female	34/30	35/32	0.010	0.919
GLU (mmol/L)	5.16 ± 0.49	5.23 ± 0.53	0.784	0.435
CR (μmol/L)	66.09 ± 13.10	68.57 ± 10.87	1.181	0.240
UA (μmol/L)	312.86 ± 70.16	298.43 ± 56.14	1.303	0.195
WBC (×109/L)	5.97 ± 1.32	5.79 ± 1.06	0.862	0.390
RBC (×1012/L)	4.62 ± 0.48	4.71 ± 0.50	1.050	0.296
HB (g/L)	140.41 ± 12.71	136.13 ± 14.77	1.774	0.078
TG (mmol/L)	1.94 ± 1.81	1.40 ± 0.89	2.182	0.031
TC (mmol/L)	5.03 ± 0.83	4.37 ± 0.41	5.810	＜0.001
HDL-C (mmol/L)	1.28 ± 0.45	1.60 ± 0.41	4.258	＜0.001
LDL-C (mmol/L)	3.52 ± 0.82	2.12 ± 0.31	13.036	＜0.001

3.2. Comparison of Various Parameters of TEG

Compared with the non-HL group, the HL group had lower R and K values and higher angle and MA values, which were statistically significant (P < 0.05) (Figure 1).

Figure 1

Comparison of various parameters of TEG. Note: indicates P < 0.05.

3.3. Comparison of Coagulation Test Indexes

Compared with the non-HL group, the PT, APTT, and INR values decreased, and the FIB values increased in the HL group, which was statistically significant (P < 0.05). The TT values in the non-HL group were similar to those in the HL group, which were not statistically significant (P > 0.05) (Figure 2).

Figure 2

Comparison of coagulation test indexes. Note: indicates P < 0.05.

3.4. Comparison of Platelet Indexes

Compared with the non-HL group, PLT values decreased, and PDW and MPV values increased in the HL group, which was statistically significant (P < 0.05) (Figure 3).

Figure 3

Comparison of platelet indexes. Note: indicates P < 0.05.

3.5. Correlation Analysis of Each Parameter of TEG and Coagulation Indexes in the HL Group

The correlation analysis among the conventional coagulation indexes, platelet indexes, and each parameter of TEG in the HL group patients was performed by using Pearson or speaeman software to analyze the correlation between the two of them. The results showed that R value was positively correlated with APTT, r= 0.373, P=0.002, which was statistically significant. K value was negatively correlated with PLT, r= −0.399, P=0.002, which was statistically significant. Α-angle and MA values were positively correlated with PLT, r= 0.319/0.475, P=0.010/P < 0.001, which was statistically significant. The rest of the indexes did not correlate with each parameter of TEG significant correlation (Table 2).

Table 2

Correlation analysis of each parameter of TEG and coagulation indexes in the HL group.

Indicators/parameters	R		K		α		MA
	r	P	r	P	r	P	r	P
PT	0.195	0.124	0.072	0.572	−0.030	0.814	−0.088	0.491
APTT	0.373	0.002∗	0.034	0.791	−0.035	0.784	0.010	0.939
FIB	−0.217	0.085	−0.182	0.150	0.212	0.092	0.127	0.319
INR	0.196	0.120	0.066	0.607	−0.023	0.858	−0.074	0.563
TT	−0.113	0.373	0.014	0.913	−0.024	0.849	−0.028	0.827
PLT	0.200	0.113	−0.388	0.002∗	0.319	0.010∗	0.475	＜0.001∗
PDW	−0.192	0.130	−0.081	0.524	0.082	0.520	0.136	0.283
MPV	−0.132	0.299	−0.086	0.506	0.089	0.486	0.168	0.184

Note. indicates that the two indicators are correlated.

4. Discussion

HL is a condition of elevated lipid levels due to abnormal fat metabolism, often accompanied by changes in blood rheology and has now become a common clinical condition, which can cause blood viscosity and is an important risk factor for complications of cardiovascular and cerebrovascular diseases [13, 14]. One study [15] confirmed that TG increases blood viscosity, promotes the production of coagulation factor VII, and is a high risk factor for venous thrombosis. High concentrations of TC can increase the deposition of TC in platelets, which in turn enhances platelet sensitivity and makes platelets more susceptible to activation and aggregation. Previous studies [16] suggest that hyperlipidemia has a more pronounced effect on the coagulation status, and timely and effective detection of coagulation in these patients can help early symptomatic management and improve patient prognosis.

Routine coagulation functions such as PT and APTT mainly target a certain stage and segment of the coagulation process and do not reflect the whole thrombosis process well. It has limited accuracy in determining hemostatic function and predicting bleeding risk in patients with important diseases and does not allow obtaining clot strength and clot stability, as these tests are detected at the beginning of the fibrin polymerization process when only about 5% of thrombin is produced and cannot evaluate the relationship between platelets and fibrinogen due to the inability to evaluate the relevant platelet function, fibrinolysis, and hypercoagulable state [17, 18]. The mechanism of TEG is based on the entire coagulation process from clotting to fibrinolysis, reflecting the interaction between the elements, with the end result being the formation of a blood clot whose physical properties determine whether the patient has normal coagulation [19]. The TEG integrates the contribution of plasma components and cellular fractions and their concentrations to coagulation during the coagulation process, and therefore, whether the changes in K, Angle, and MA values of the TEG are indicative of the state of coagulation caused by HL.

The R value reflects the combined effect of factors participating in coagulation, including endogenous, exogenous, and common coagulation pathways, and a decrease in R value represents hypercoagulation. Both K and α angle reflect the rate of clot formation, the size of which depends on the levels of coagulation factors, platelets, and fibrinogen; MA reflects the strength of the clot after formation [20, 21]. In this study, 64 patients with HL and 67 patients with non-HL, the results of the study concluded that the R value, K value, PLT value, PT, APTT, and INR value decreased, and the angle value, MA value, FIB value, PDW, and MPV value increased in HL patients. Decreased PT and APTT values indicate that HL patients are more active in endogenous and exogenous coagulation pathways than non-HL patients, all of which leads to the conclusion that HL patients have more hypercoagulable blood than non-HL patients. In addition, correlation analysis showed that K values were negatively correlated with PLT values, and α angle and MA values were positively correlated with PLT values. The most commonly used method for clinical evaluation of platelet aggregation function is TEG, which can reflect not only the abnormalities in various parts of the coagulation process in patients but also the changes in platelet function before and after the application of antiplatelet aggregation drugs in patients and evaluate whether patients are sensitive or resistant to the drugs [22]. Based on the results of this study, it can be hypothesized that the coagulation system is relatively active in HL patients, with more prothrombin and fibrin content than in nonhyperlipidemic patients.

In summary, TEG can infer the HL and HL status of blood by the changes of the K value, angle, and MA values, suggesting the effect of HL on the coagulation status, which is important for guiding the adjustment of lipid-lowering, antithrombotic, and anticoagulation regimens in patients with atherosclerosis combined with HL or postsurgical combined with HL.