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RESEARCH ARTICLE
Year : 2017  |  Volume : 2  |  Issue : 4  |  Page : 7-10

Hemostasis and clotting markers and its significances in unstable angina pectoris patients complicated with diabetes mellitus


1 Department of Cardiology, Hainan People's Provincial Hospital, Haikou, 570311, China
2 Institute of Cardiovascular Disease, Tongji Medical College, Huazhong University of Science and Techology, Hankou, 430022, China

Date of Web Publication12-Mar-2018

Correspondence Address:
Jian-lin Ma
Department of Cardiology, Hainan People's Provincial Hospital, Haikou 570311
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cp.cp_2_17

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  Abstract 

Background: Recent studies have confirmed that patients with unstable angina pectoris (UAP) complicated with diabetes mellitus(DM) have obvious per-thrombosis state. However, it is not clear that the changes of the hemostasis and clotting markers are very clear. Therefore, this paper is to determine the hemostasis and clotting markers in patients with UAP complicated with DM and those without DM and compared with the control group. Methods: Forty patients with UAP, forty patients with UAP complicated with DM, and forty healthy participants were included in the study as UAP group, complication group, and control group, respectively. Levels of platelet membrane glycoprotein(GP), Von Willebrand (vWF), plasminogen, antithrombin III(ATIII), factor VIII-related antigen(VIII: Ag), platelet membrane glycoprotein-140(GMP-140), protein C(PC), factor II activity(FIIa), tissue plasminogen activity(t-PA), PA inhibitor(PAI), D-dimer, and thromboxane B2(TXB2) were measured in all groups. Results: Compared with a control group and UAP group, there were significant changes of GP, vWF, ATIII, VIII: Ag, GMP-140, PC, FIIa, t-PA, PAI, D-dimer, and TXB2 in complication group (P<0.05, or P <0.01). Compared with control group, there were significant changes of GP, vWF, ATIII, VIII: Ag, GMP-140, PC, FIIa, t-PA, PAI, D-dimer, and TXB2in UAP group (P <0.05, or P <0.01). Conclusions: There are significant changes of hemostasis and clotting markers in patients with UAP, especially in those complicated with DM, which may be an important reason for the poor prognosis of these patients.

Keywords: Diabetes mellitus, hemostasis and clotting markers, unstable angina pectoris


How to cite this article:
Ma Jl, Zhou Y, Zhang Jm, Ma Ln, Li H, Ma X, Wang L. Hemostasis and clotting markers and its significances in unstable angina pectoris patients complicated with diabetes mellitus. Cardiol Plus 2017;2:7-10

How to cite this URL:
Ma Jl, Zhou Y, Zhang Jm, Ma Ln, Li H, Ma X, Wang L. Hemostasis and clotting markers and its significances in unstable angina pectoris patients complicated with diabetes mellitus. Cardiol Plus [serial online] 2017 [cited 2018 Sep 24];2:7-10. Available from: http://www.cardiologyplus.org/text.asp?2017/2/4/7/227168




  Introduction Top


Recent studies have showed that there are obvious per-thrombosis state (PTS) in patients with UAP especially in those complicated with diabetes mellitus (DM). The factors such as insulin resistance, tissue hypoxia, nerve endocrine disorders contribute to the marked changes of markers of PTS in patients with UAP complicated with DM. However, it is not clear that the changes of the hemostasis and clotting markers are very clear. To research the changes of hemostasis and clotting markers in patients with UAP complicated with DM, this paper is to determine the hemostasis and clotting markers in patients with UAP complicated with DM and those without DM and compared with the control group and analyzed its clinical significance.


  Methods Top


From July 2014 to September 2016, forty patients with unstable angina pectoris (UAP) forty patients with UAP complicated with DM, and forty healthy participants were included in the study as UAP group, complication group, and control group, respectively. According to the principle of medical ethics, all patients were given with nitrate medications, beta-blockers, aspirin, clopidogrel, and statins. If angina pectoris events occur, they were treated with nitroglycerin, beta-blockers, and low molecular heparin. UAP group consisted of 29 males and 11 females, with an average age of 60.8 ± 9.6. Complication group consisted of 28 males and 12 females, with an average age of 60.3 ± 9.1. Control group consisted of 27 males and 13 females, with an average age of 60.5 ± 9.2.

All patients with coronary artery disease (CAD) were admitted to the hospital for 7 days and underwent selective coronary angiography. CAD is defined as at least one epicardial coronary artery with a narrow >50% diameter (visual method). Angiography results: In UAP group, there were 13 cases of single-vessel lesions, 27 cases of multivessel diseases (8 cases of double vessel diseases, 11 cases of 3 vessel diseases, and 8 cases of 3 vessels with left main vessel diseases), among them 11 cases with diffuse lesions. In complication group, there were 8 cases of single-vessel lesions, 32 cases of multivessel lesions (8 cases of double vessel diseases, 11 cases of 3 vessel diseases, and 13 cases of 3 vessels with left main vessel diseases), among them 31 cases with diffuse lesions.

A volume of 10 ml of blood specimens was taken from the peripheral venous in all of the study participants in the morning with empty stomach. If there were angina pectoris attacks, second specimens should be taken within 12 h (the results of second specimens were included in the statistics).

Patients with serious liver and kidney disease or acute infection, cerebrovascular disease, hematological disease, and myocardial infarction were excluded from the study.

Experimental protocol

According to the principle of medical ethics, all patients were given with nitrate medications, beta blockers, aspirin, and clopidogrel; 10 ml of blood specimens was taken from the peripheral venous in the morning with empty stomach, if there were angina pectoris attacks, the specimens should be taken within 12 h. The blood was centrifuged for 10 min at the rate of 3000 rpm, and then the plasma (or serum) was separated and stored at −70.

The serum Von Willebrand (vWF), plasminogen (Plg), antithrombin III (ATIII), and VIII-related antigen (VIII: Ag) were measured by immune turbidity method with Shanghai sun Biological Technology Company Kit.

The plasma GMP-140, protein C (PC), factor II activity (FIIa), tissue Plg activity (t-PA), Plg activity inhibitor (PAI), and D-dimer were measured by the method of double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) chromogenic substrate. The plasma was measured by the method of immune nephelometry. The plasma thromboxane B2 (TXB2) was measured by ELISA.

Platelet membrane glycoproteins (GP) Ib, IIb, and IIIa were measured by competitive ELISA, expressed in terms of the number of GP molecular in each platelet (molecular/between blood platelet count). This study was approved by the Hospital Medical Ethics Committee.

Statistical analysis

Statistical data were analyzed by the Statistical Package for Social Sciences, version 23.0 (SPSS, Chicago, IL, USA). Continuous variables were expressed as mean ± standard deviation (SD). The measurement data between groups and within groups were statistically analyzed with F test and q test, and numeration data with chi square test respectively. A value P < 0.05 was considered statistically significant.


  Results Top


Comparison of basic data among the three groups

There were more cases of coronary artery lesion, diffuse disease, heart function Grade III in complication group than UAP group (all P < 0.01), and level of blood glucose (BG) in complication group was also higher than that in the UAP group (P < 0.01). There was no significant difference in sex, age, smoking, systolic blood pressure, diastolic blood pressure, scerum creatine(SCr), blood uric acid (UA), total cholesterol (TC), and triglyceride (TG) between complication group and UAP group (all P > 0.05) [Table 1].
Table 1: Comparison of basic data among the three groups (X±S)

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Comparison of glycoprotein Ib, glycoprotein IIb, and glycoprotein IIIa among the three groups

Compared with UAP group and control group, there were significant changes of GPIb, GPIIb, and GPIIIa in complication group (P< 0.05 or P < 0.01). Compared with control group, there were significant changes of GPIb, GPIIb, and GPIIIa in UA group (all P < 0.05) [Table 2].
Table 2: Comparison of glycoproteins Ib, glycoproteins IIb, glycoproteins IIIa among the three groups (molecular [×104]/BPC, X±S)

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Comparison of hemostasis and clotting markers among the three groups

Compared with the data in UAP group and control group, there were significant changes of vWF, VIII: Ag, ATIII, GMP-140, PC, FIIa, fibrinogen (Fbg), t-PA, PAI-1, D-Dimer, and TXB2 in complication group (all P< 0.01). Compared with the data in control group, there were significant changes of vWF, VIII: Ag, ATIII, GMP-140, PC, FIIa, Fbg, t-PA, PAI-1, D-Dimer, and TXB2 in UA group (P< 0.05 or P < 0.01), but levels of plasma Plg were no significant differences among the three groups (all P > 0.05) [Table 3].
Table 3: Comparison of per-thrombosis state molecular markers among the three groups (X±S)

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  Discussion Top


Modern studies at home and abroad have confirmed that patients with unstable angina have obvious PTS, which shows the imbalance of coagulation and anticoagulant system in vivo and the body is in favor of thrombosis. Among them, the pathological mechanism in patients with pectoris angina events is based on CAD and PTS, microthrombosis in coronary artery, leading to myocardial ischemia and hypoxia, then the impact of the dynamic process of thrombosis. In this process, DM is an important risk factor for patients with unstable angina pectoris.

The result showed that levels of sex, age, smoking, blood pressure, serum creatinine, blood uric acid, TC, and TG between complication group and UAP group were no significant differences (all P > 0.05), but levels of BG in complication group were significantly higher than UAP group (P< 0.01). In this article, the results of coronary angiography showed that coronary vascular lesion and diffuse disease in complication group were significantly higher than UAP group, and the cases of cardiac function Grade III in complication group were also significantly higher than UAP group. The complication group of CAD is relatively severe and poor heart function, which may be associated with diabetes in patients with insulin resistance, nerve endocrine abnormalities, and glucose metabolic disorder caused by increasing the degree of coronary artery lesions.

The study has shown that there are obvious changes of hemostasis and clotting markers in patients with UAP, especially in those complicated with DM. The study found that the number of GPIb, GPIIb, and GPIIIa in patients with UAP complicated with DM was significantly higher than those in patients without DM, indicate that there was a significant platelet activation in those complicated with DM. Activated platelets can act as adhesion molecules on receptor sites and mean that the GPIIb/IIIa complex acts as a FIB receptor in combination with FIB, linking platelets to the underlying endothelium to form platelet thrombus.[1]

This study has found that levels of GMP-140 in the patients with UAP complicated with DM are obviously increased, which shows that the activity of thrombocyte is increased. GMP-140 is released in platelet granules that can modulate the interaction between platelet and vascular endothelial cells and leukocyte, which causes the change of platelet membrane phospholipids and arachidonic acid metabolisms and then produces TXA2. Meanwhile, the secretion of PGI2 is reduced, leading to platelet activation and coagulation.[1],[2],[3]

The study has confirmed that levels of vWF, factor VIII related antigen, and FIIa in patients with UAP complicated with DM are significantly increased, but the levels of ATIII are significantly decreased. As the bearer of factor VIII and vWF, together with the procoagulant part of the low molecular weight VIII factor, forms the complex involved in the coagulation process.[1] Thrombin is mainly through the catalytic conversion of Fbg into fibrin monomers, promote blood coagulation, thus accelerating the formation of PTS.[4],[5] The formation of PTS can be accelerated by decreases of ATIII, the mechanism may be related to ATIII excessive consumption, vascular endothelial dysfunction, and lipid peroxidation injury.[6],[7]

It has revealed that t-PA activity was decreased, whereas PAI-1 activity was increased markedly in patients with UAP complicated with DM, indicating fibrinolytic dysfunction, the mechanism may be related to catecholamine and rennin–angiotensin system to stimulate PAI synthesis.[8],[9]

The result of this study shows that there were no significant differences of Plg among UAP group, complicated group, and control group or those complicated with DM compared with the control group. The mechanism may be that there is a dynamic balance between the production and consumption of Plg in the pathological state.


  Conclusions Top


There are significant changes of hemostasis and clotting markers such as GP, vWF, Plg, ATIII, VIII: Ag, GMP-140, PC, FIIa, t-PA, PAI, D-dimer, and TXB2 in patients with UAP, especially in those complicated with DM, which may be an important reason for the poor prognosis of these patients.

Financial support and sponsorship

This work was supported by Science and Technology Planning Project of Hainan Province (20158328).

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Boesch P, Weber-Lotfi F, Ibrahim N, Tarasenko V, Cosset A, Paulus F, et al. DNA repair in organelles: Pathways, organization, regulation, relevance in disease and aging. Biochim Biophys Acta 2011;1813:186-200.  Back to cited text no. 2
    
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Smirnova IV, Bokarev IN. The activity of willebrand factor – Glycoproteins IIb/IIIa complex in patients with coronary and low extremity arterial atherothrombosis and type 2 diabetes mellitus. Klin Med (Mosk) 2007;85:34-9.  Back to cited text no. 5
    
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Sabatine MS, Braunwald E. Will diabetes save the platelet blockers? Circulation 2001;104:2759-61.  Back to cited text no. 6
    
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Chistiakov DA, Sobenin IA, Bobryshev YV, Orekhov AN. Mitochondrial dysfunction and mitochondrial DNA mutations in atherosclerotic complications in diabetes. World J Cardiol 2012;4:148-56.  Back to cited text no. 7
    
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Pottier P, Fouassier M, Hardouin JB, Volteau C, Planchon B. D-dimers, thrombin-antithrombin complexes, and risk factors for thromboembolism in hospitalized patient. Clin Appl Thromb Hemost 2009;15:666-75.  Back to cited text no. 8
    
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Heitzer T, Schlinzig T, Krohn K, Meinertz T, Münzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 2001;104:2673-8.  Back to cited text no. 9
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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