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 Table of Contents  
Year : 2020  |  Volume : 45  |  Issue : 1  |  Page : 23-27

Initially presented acute coronary syndrome: does D-dimer imply any clinical significance?

1 Departments of Cardiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
2 Departments of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Date of Submission22-Sep-2019
Date of Acceptance26-Oct-2019
Date of Web Publication10-Sep-2020

Correspondence Address:
Yasmin N El-Sakhawy
Assisstant Professor Clinical Pathology Department, Ain Shams University, Egypt
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ejh.ejh_40_19

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Background D-Dimer is an enzymatic degradation product that is formed as a result of breakdown of cross-linked fibrin clots by plasmin. The plasma level of D-dimer is vital for evaluating the patient’s fibrinolytic status. D-dimer testing was proven to be beneficial marker in the identification of deep vein thrombosis of the lower limbs and pulmonary embolism [16]. The relationship between the level of D-dimer levels & acute coronary syndrome is uncertain and conflicting.
Aim The aim of this study was to assess D-dimer levels in patients presented to the emergency room (ER) with acute chest pain.
Subjects and methods The first group involved those diagnosed with acute coronary syndrome (ACS); which included unstable angina pectoris [UA], non-ST elevated myocardial infarction [NSTEMI], ST-elevated myocardial infarction [STEMI]); the control group involved those diagnosed with non-cardiac chest pain. The serum levels of D-dimer, creatine kinase-MB (CK-MB) and troponin I (TPI) were assessed in the two groups.
Results Levels of D-dimer, CK-MB and TPI was higher in the patient group. There were also higher D-dimer, CK-MB and TPI levels in the STEMI and NSTEMI patient subgroups as compared with the control group. Merely the D-dimer level was higher in the UA subgroup as compared with the control group.
Conclusion D-dimer levels assessment seemed to be useful in the ER for identifying ACS patients and to predict mortality hazards in patients presenting with acute chest pain.

Keywords: acute coronary syndrome, chest pain, D dimer, emergency room

How to cite this article:
Mansour HM, El-Sakhawy YN. Initially presented acute coronary syndrome: does D-dimer imply any clinical significance?. Egypt J Haematol 2020;45:23-7

How to cite this URL:
Mansour HM, El-Sakhawy YN. Initially presented acute coronary syndrome: does D-dimer imply any clinical significance?. Egypt J Haematol [serial online] 2020 [cited 2020 Dec 3];45:23-7. Available from: http://www.ehj.eg.net/text.asp?2020/45/1/23/294782

  Introduction Top

Failure to diagnose patients who have acute coronary syndromes (ACSs), either acute myocardial infarction (MI) or unstable angina pectoris (USAP), who present to the emergency department remains a serious public health issue [1]. The analysis of ischemic chest pain in the emergency room is dependent on history, biomarkers, and ECG results [2]. Serial ECG and serum enzyme measurements are very important for the diagnosis of MI and USAP but have inadequate diagnostic value in the initial stages of these syndromes. Cardiac enzyme levels may take several hours to increase after pain begins, and the ECG has imperfect sensitivity for the initial diagnosis of MI [3],[4].

ACS happens when an unstable plaque ruptures and activates coagulation at the site, obstructing blood flow and producing ischemic damage to the heart. Thrombogenesis is the last step whereby exposed tissue factor causes the initiation of coagulation and the freshly made clot fills the coronary artery lumen. Numerous biochemical markers of thrombus formation including fibrinogen, prothrombin fragment, thrombin–antithrombin complex, and fibropeptide A have been linked with an augmented threat of MI [5]. D-dimer is the main degradation product of cross-linked fibrin and, consequently, helps as a direct indicator of continuing coagulation with fibrinolysis [6]. D-dimer has also been associated well with consequent coronary artery events [7].

The aim of the current study was to explore the indicative potential of the serum D-dimer level for ACS in patients presented to the emergency department experiencing chest pain.

  Patients and methods Top

Patient population and study design

Following approval from the Ethical Committee Presidency of Faculty of Medicine University of Ainshams, Cairo, Egypt, this study was done out on patients admitted to the Emergency Department of Ain shams University Hospital between March 2016 and April 2018, because of sudden-onset chest pain.

Exclusion criteria included, first, patients presenting with chest pain who had a diagnosis and treatment started within the previous 7 days; second, patients who had experienced coronary artery bypass grafting, angioplasty, or open-heart surgery within the prior 6 months; third, patients admitted with other causes known to elevate D-dimer level (e.g. upper gastrointestinal bleeding, acute intestinal ischemia, ischemic and hemorrhagic stroke, deep vein thrombosis, sepsis, and malignancy); and fourth, patients admitted more than 12 h after chest pain onset.

A standard study was done, and patient agreement forms were filled in by all patients. Routine blood samples, cardiac enzymes measurements, D-dimer measurements, and an ECG were assessed for all patients.

All patients were assessed by a cardiology specialist. Those experiencing chest pain and established as having ACS were recognized as the patient group, and those established with noncardiac chest pain were recognized as the control group. Patients who were determined to be non-ischemic in the control group were scheduled for an exercise stress test. Only patients in whom the test results were negative were included in the control group.

ACS includes USAP, non-ST elevated MI (NSTEMI), and ST elevated MI (STEMI) [8]. Patients with typical resting chest pain lasting more than 20 min, in whom chest pain had begun as a novel complain within the preceding 2 months and in whom the strength of the pain had augmented, together with no rise in myocardial enzymes, were defined as the USAP subgroup. Those patients with typical chest pain lasting more than 30 min, in whom cardiac enzymes were elevated following ST segment depression and T-wave inversion, were included in the NSTEMI subgroup. Patients who had ST segment elevation in two or more ECG contagious leads (≥1 mm), together with elevated levels of myocardial enzymes and troponin I (TPI), were incorporated in the STEMI subgroup.

Laboratory investigations

Five milliliters of venous blood was withdrawn under aseptic condition from patients and control groups on admission to Emergency Department. Three milliliters of venous blood was collected in a blank gel tube for measurement of cardiac enzymes. Two milliliters of venous blood was collected from the patients on a trisodium citrate vacutainer (one part of citrated sodium: 0.109 mmol/l with nine parts of venous blood) for measuring D-dimer levels.

Serum was separated by centrifugation at 3000 g for 15 min. CK-total was assayed spectrophotometrically on the synchron CX9 autoanalyzer (Beckman Instruments Inc., USA), which measures CK-total activity by an enzymatic rate method. Creatine kinase-MB (CK-MB) was assayed spectrophotometrically on the synchron CX9 autoanalyzer (Beckman Instruments Inc.) by the immune-inhibition technique. Cardiac troponic I (cTn-I) was assayed using Architect I 1000 from Abbott Diagnostics System (USA). The used method is a two-step assay based on chemiluminescent microparticle immunoassay.

Platelet-poor plasma was obtained by centrifugation at 3000g in room temperature. Quantitative determination of D-dimer was done using the INNOVANCE D-dimer assay, an automated, particle-enhanced, immunoturbidimetric assay for the cross-linked fibrin degradation products (D-dimers) in human plasma on Sysmex CA-1500 (Siemens Diagnostics, Germany). The results were expressed in mg/l FEU.

Statistical analysis

Data were collected, revised, and entered into the statistical package for the social sciences (IBM SPSS) version 21(SPSS 21; IBM, Armonk, New York, USA). Qualitative data were presented as numbers and percentages, whereas quantitative data were entered into Kolmogorov–Smirnov test of normality, and parametric distribution data were presented as mean, SD, and range. To compare parametric quantitative variables between the two groups, Student’s t-test was applied. For within-group evaluations, single-direction Kruskal–Wallis variance analysis and the Mann–Whitney U-test as a various evaluation methods were assessed. The comparison between the two groups with qualitative data was done using χ2-test. A one-way analysis of variance was used when comparing between more than two means. Post-hoc test was used for multiple comparisons between the different variables. The association between two variables among normally distributed data was done by Pearson’s correlation and by Spearman’s correlation among nonparametric data. The cutoff levels determined for D-dimer, CK-MB, and TPI were 0.5 mg/l, 24 U/l and 1.00 ng/ml, respectively. The sensitivity and specificity of these cardiac markers for identifying ACS were measured. For between-group comparisons, a P value less than 0.01 was reflected to be statistically significant; for all other comparisons, a P value less than 0.05 was reflected to be statistically significant.

  Results Top

Of a total of 600 patients with sudden-onset chest pain who were admitted to the Emergency Department of Ain Shams University Hospital, 480 were included in this study according to inclusion and exclusion criteria. Of these, 300 (62.5%) patients were included in the patient group and 180 (37.5%) consisted the control group. Regarding the patient group, 59.3% (n=178) were male and 40.7% (n=122) were female. The mean±SD age was 61.82±11.2 years (range: 34–90 years), and the mean±SD admission time was 4.66±2.07 h (range: 1–12 h). Of the control group, 67.0% (n=59; 120) were male and 33.0% (n=60) were female, with a mean±SD age of 60.40±9.48 years. No significant difference was found between the control and patient groups in terms of mean age and sex distribution. When the patient group was classified according to the ACS subtypes, 28% (n=84) represented the USAP subgroup, 35.3% (n=106) represented the NSTEMI subgroup, and 36.7% (n=110) represented the STEMI subgroup.

Laboratory data

Levels of CK-MB, TPI, and D-dimer for both groups are represented in [Table 1]. When the control and patients groups were compared according to their ACS subtype, there was a statistically significant difference in the levels of CK-MB, TPI, and D-dimer (P<0.001) between the STEMI and NSTEMI subgroups and the control group ([Table 2]). There was a statistically significant difference between the USAP subgroup and the control group for D- dimer levels only (P<0.001). When the STEMI and NSTEMI subgroups were compared, there were no substantial differences in the levels of CK-MB, TPI, and D-dimer ([Table 2] and [Table 3]).
Table 1 The level of cardiac biomarkers and D-dimer in patient and control groups

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Table 2 Levels of cardiac markers and D-dimer in subgroups of patients group and control group

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Table 3 Sensitivity and specificity of D-dimer, creatine kinase-MB, and troponin I levels to identify acute coronary syndrome in patients admitted to the emergency department with acute chest pain

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The cutoff values of D-dimer, CK-MB, and TPI were 0.5 mg/l, 24 U/l, and 1.0 ng/ml, respectively.

Regarding the relation between mortality level of cases and D-dimer levels, 10 (3.3%) patients from the ACS patient group died; six of the dead patients had STEMI and four had NSTEMI. A substantial difference was observed between mean serum D-dimer concentrations in living and dead patients (2.01±1.91 and 6.51±3.80 µg/ml, respectively; P=0.005). No significant difference was observed between mean serum CK-MB and TPI concentrations in living and dead patients.

  Discussion Top

Chest pain is a very common cause for presentation to the emergency room, and the rapid evaluation and diagnosis of the cause of acute chest pain is essential and often problematic for emergency physicians [9]. In some patients having a pre-existing cardiac abnormality, such as left ventricular hypertrophy or prior MI, the first ECG is uncertain and cannot be used to reach a diagnosis [10]. In many studies, 5% of patients who were discharged from the emergency department because of normal ECG finding were later identified as having ACS [11],[12]. Therefore, there is a need for reliable cardiac biomarkers that can be used to recognize these unrecognized patients with ACS before they are prematurely discharged from the Emergency Department.

TPI and CK-MB are normally used in the assessment of ACS, but their levels are not raised during the initial few hours following symptom onset, and their effectiveness in the early diagnosis of chest pain is uncertain. Being involved in an earlier stage in the pathophysiological process of MI and USAP, D-dimer is considered one of the more beneficial biomarkers in ACS. D-Dimer levels do rise before cardiac injury biomarkers (including myoglobin) in acute ischemic events [13].

D-dimer is an enzymatic degradation product that is formed as a result of breakdown of cross-linked fibrin clots by plasmin. The plasma level of D-dimer is vital for evaluating the patient’s fibrinolytic status [12]. D-Dimer testing was proven to be beneficial marker in the identification of deep vein thrombosis of the lower limbs and pulmonary embolism [14]. However, regarding the relationship between the level of D-dimer levels and ACS, published data are conflicting. For example, small studies showed that D-dimer levels are greater in patients with MI than in patients with other subtypes of ACS [15],[16]. In contrast, another study found normal D-dimer levels in patients with MI compared with healthy people [17]. In a study of 300 patients presented to the emergency department with acute chest pain, Bayes-Genis et al. [13] revealed that D-dimer levels in acute MI and USAP were significantly elevated secondary to MI. Similarly, in the current study, serum D-dimer levels were considerably higher in patients presented to the emergency department with chest pain with a later diagnosis of ACS, in comparison with the levels in those admitted with noncardiac chest pain.

CK-MB, myoglobulin, and TPI are commonly used as biomarkers of ACS, but these biomarkers directly indicate the injury to myocardium and do not indicate coronary thrombosis. Markers that reveal the obstructive events in the coronary arteries would be more beneficial than those imitating the damage to myocardium [18]. Raised D-dimer levels could reveal a generalized prothrombotic state and, possibly, focal vessel-wall-related fibrin formation and degradation associated with unstable atherosclerotic plaque activity [19]. D-Dimer and plasmin–plasmin inhibitor complex levels in the acute phase of ACS were considerably higher than those in the recovery phase, proposing intracoronary thrombosis [20]. Specifically, D-dimer levels were elevated in the peripheral blood of patients with USAP, without overlap with levels in patients with stable angina [21]. In another study, D-dimer levels were greater in patients presented to the emergency department with normal ECG and USAP [22]. Moreover, in the current study, only the D-dimer level was considerably greater in patients with USAP when compared with the control group, whereas there were no significant differences in the CK- MB and TPI levels. For this reason, Bayes-Genis et al. [13] proposed that serum D-dimer levels should be studied, in addition to other cardiac markers, in patients presenting to the emergency department with acute chest pain and normal ECG findings.In addition, Reihani and colleagues stated that noticeable upsurges in circulating D-dimer were suggestive of thrombotic complications in patients with MI, suggesting that D-dimer, besides being a useful marker for initial diagnosis, is similarly a hazardous element for the development of MI complications [23]. Moreover, Oldgren and colleagues found that on long-term follow-up (median: 29 months) for patients with USAP, higher baseline levels of D-dimer at diagnosis are related to increased mortality in these patients [24]. Of the 10 patients in this study who died during the period of the study, six had STEMI, four had NSTEMI, and none had USAP. Levels of D-dimer levels were considerably higher in patients who died compared with those who lived, and there were no statistical differences in CK-MB and TPI levels between survivors and nonsurvivors. These findings propose that D-dimer levels are more appreciated than CK-MB and TPI levels in expecting mortality, although it should be noticed that the patient numbers in the present study were low.

  Conclusion Top

In conclusion, plasma D-dimer levels seem to be valuable in diagnosing ACS and might assist in the prediction of mortality, in patients presenting to the emergency department with acute chest pain.

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Conflicts of interest

There are no conflicts of interest.

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  [Table 1], [Table 2], [Table 3]


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