Sage Journals: Discover world-class research

Abstract

This study aimed to investigate the significance of the prethrombotic state (PTS) and 4 plasma markers in predicting perisurgical adverse cardiac events in patients with coronary heart disease (CHD) undergoing abdominal surgery. Perioperative adverse effects were recorded in 128 consecutive patients with CHD undergoing elective abdominal surgery. Plasma d-dimer, P-selectin, von Willebrand factor (VWF), and thrombus precursor protein were measured before and after the surgery. Patients with abnormal values in one or more of the 4 PTS markers were identified as having PTS, and data were analyzed by univariate and multivariate logistic regression. Abnormal presurgery levels of the 4 markers were found more frequently in those with adverse perioperative cardiac events than in those without. Multivariate analysis showed the odds ratios for adverse cardiac events to be 64.3 (PTS, P < .001), 25.7 (VWF, P = .003), and 23.5 (P-selectin, P = .04). Preoperative PTS is an independent risk factor for perioperative events in patients with CHD undergoing noncardiac surgery.

Keywords

coronary heart disease noncardiac surgery adverse cardiac events prethrombotic state

Introduction

The prethrombotic state (PTS), also known as the hypercoagulable state, refers to a pathological condition characterized by an imbalance in coagulation and anticoagulation factors.¹ Previous studies have shown that patients with coronary heart disease (CHD) usually develop PTS^2,3 and that perioperative adverse cardiac events are closely related to abnormalities in coagulation function (especially the PTS). However, little attention has been paid to this relationship in clinical practice, and to date, few clinical studies have investigated the correlation between PTS and perioperative adverse cardiac events. The present study aimed to investigate the significance of 4 plasma markers of PTS (d-dimer, thrombus precursor protein [TpP], P-selectin, and von Willebrand factor [VWF]) in predicting adverse cardiac events in clinical practice.

Materials and Methods

Selection of Patients

The present study was approved by the ethics committee of the First Affiliated Hospital of Xinjiang Medical University and informed consent was obtained from each patient before the study. A total of 128 consecutive patients with CHD (stable angina or old myocardial infarction) who received abdominal surgery in our hospital were recruited from October 2010 to August 2011.

Inclusion Criteria

Inclusion criteria included the following: age 61 to 75 years; elective abdominal surgery with moderate to high risk (general abdominal surgery, urinary surgery or gynecological surgery) and a surgery time of 90 to 180 minutes; CHD diagnosed according to the World Health Organization criteria for CHD; stable angina or old myocardial infarction (6 months); cardiac function completely evaluated preoperatively as New York Heart Association class I-II; prothrombin time, presurgery activated partial thromboplastin time, thrombin time, fibrinogen, and platelet count in the normal range; and informed consent was obtained before surgery

Exclusion Criteria

Exclusion criteria were the following: emergency surgery or low-risk surgery; concomitant severe infection; dysfunction of liver, spleen, kidney, or lung; malignancies; concomitant congenital heart disease, cardiomyopathy, rheumatic heart disease, pulmonary heart disease, severe heart failure, or severe arrhythmia; unstable angina or myocardial infarction within the previous 6 months; hematological disease; intraoperative blood loss exceeding 20% of blood volume; inability (psychiatric disorders, consciousness disturbance, mental retardation) to cooperate with clinicians; and blood-borne infectious diseases (hepatitis B, hepatitis C, syphilis, and AIDS).

Data Collection

Levels of d-dimer, P-selectin (CD62-P), TpP, VWF, and cardiac troponin I (cTnI) were measured preoperatively on the day of surgery (T1), and 24 (T2), 48 (T3), and 72 (T4) hours after surgery because adverse cardiac events are frequently found within 3 days after surgery. Electrocardiography was performed 30 minutes, 24 hours, 48 hours, and 72 hours after the surgery. Blood pressure, heart rate, saturation of peripheral oxygen (SPO₂), intraoperative blood loss, volume of supplemental fluid administered, urine volume, and changes in the ST segment were measured during the surgery, and patients were followed up for 30 days.

Primary variables were the 4 markers for determination of PTS, d-dimer, P-selectin, VWF, and TpP. The PTS was defined when any one of them was abnormal. Secondary variables were electrocardiogram changes and cTnI. In addition, we measured intraoperative blood pressure, heart rate, SPO₂, blood loss, volume of supplemental fluid administered, and urine volume.

Sample Collection and Measurement

The EDTA-K2 anticoagulated whole blood (2.0 mL) was collected for the measurement of P-selectin. Sodium citrate (1:9) anticoagulated whole blood (5 mL) was collected for the measurement of plasma d-dimer, VWF, and TpP. Heparin anticoagulated whole blood (4.0 mL) was collected for the measurement of cTnI. Flow cytometry was performed to measure P-selectin within 2 hours after sample collection, using an Epics XL flow cytometer (Beckman Coulter, cytomics Fc500, USA). Turbidimetric immunoassay was performed to detect d-dimer within 4 hours after sample collection, using an ACL-Advance Coagulation Analyzer (AuTop, USA) (Instrumentation Laboratory International, Enzyme Bio-Radxmark, Bio-Rad, USA). Enzyme-linked immunosorbent assay was performed to measure TpP and VWF. P-selectin antibody, and kits for TpP and VWF determination were purchased from B&D Systems (Becton-Dickinson, Atlanta). The normal ranges for d-dimer, P-selectin, TpP, and VWF were 0 to 278 ng/mL, 0.2% to 1.4%, <5.5 mg/L, and 60% to 150%, respectively. Abnormal values for these parameters were defined as any value above the normal range.

End Point Events: Adverse Cardiac Events

Adverse cardiac events included myocardial ischemia, myocardial infarction, arrhythmia, congestive heart failure, cardiac death, and so on. The criteria for the diagnosis of individual adverse cardiac events were (1) myocardial ischemia: horizontal or down-sloping ST-segment depression of ≥1 mm or elevation of ≥ 2 mm at 80 milliseconds after the J point; (2) myocardial infarction: precordial pain continued for 30 minutes, and Q wave, depression, or arched elevation of ST segment and cTnI >3.1 g/L; (3) arrhythmia: evident symptoms of atrial fibrillation, paroxysmal supraventricular tachycardia, or premature ventricular contraction affecting hemodynamics or requiring pharmacotherapy; (4) congestive heart failure: shortness of breath, jugular vein distention, gallop rhythm, and pulmonary edema on chest x-ray; (5) cardiac death: death from cardiac events including myocardial infarction, heart failure, arrhythmia, and so on. These events were used as a single cumulative end point.

Statistical Analysis

Continuous data are presented as median with interquartile range; categorical data are presented as count (percentage). Differences between those with and without adverse cardiac events for continuous and categorical data were tested with the nonparametric Mann-Whitney test and Fisher exact test, respectively. Changes in d-dimer, TpP, P-selectin, and VWF during the 3 days from preoperation to postoperation were tested with the Friedman test, and changes between each 2 time points were tested with the Wilcoxon signed ranks test with the Bonferroni correction for type I error. Logistic regression analyses were performed to evaluate the risk factors for adverse cardiac events. Variables with P value <.1 in the univariate logistic regression analysis were then entered stepwise into the multivariate analysis by the forward conditional method. To avoid serious colinearity in the multivariate analysis, 2 multivariate analyses were performed, 1 that included 3 markers of PTS (d-dimer, P-selectin, and VWF) but not the PTS itself, and 1 included PTS instead of the 3 markers. The odds ratio (OR) for TpP could not be calculated in the univariate analysis because the number of patients in the nonadverse cardiac event group with abnormal preoperative values was zero. Therefore, it was not included in the multivariate analysis. All statistical assessments were 2-sided. P value <.05 was considered to be statistically significant. Statistical analyses were performed using SPSS 15.0 statistics software (SPSS Inc, Chicago, Illinois).

Results

Participants

During the period from October 2010 to August 2011, 138 patients fitting the inclusion and exclusion criteria were prospectively enrolled in the study. The follow-up period was 30 days; 10 patients who were lost to follow-up were excluded from the analysis. The remaining 128 patients included 96 (75.0%) males and 32 (25.0%) females, with a median age of 64. In all, 29 (22.7%) of these patients experienced 1 or more adverse cardiac events during or after the surgery.

Association Between Patient Characteristics and Adverse Cardiac Events

The patient group that experienced adverse cardiac events was older (67.0 vs 64.0 years, P = .022) and had a higher percentage of individuals with nonHan Chinese ethnicity (51.7% vs 29.3%, P = .044) than the group without adverse cardiac events. Patients who had adverse cardiac events also had a higher body mass index (24.2 vs 22.7 kg/m², P < .001) were more likely to be obese (27.6% vs 7.1%, P = .006) and were more likely to have a history of diabetes mellitus (37.9% vs 8.1%, P < .001) and a history of coronary stenting or coronary artery bypass graft surgery (48.3% vs 16.2%, P = .001). In addition, the duration of surgery in those with adverse cardiac events was significantly longer than in those without adverse cardiac events (150 vs 120 minutes, P < .001; Table 1).

Table 1.

Summary of Characteristics of Patients With and Without Adverse Cardiac Events.^a

		Adverse Cardiac Events (n = 29)	No Adverse Cardiac Events (n = 99)	P Value
Age, years		67.0 (65.0, 71.0)	64.0 (61.0, 73.0)	.022^b
Gender	Male	18 (62.1%)	78 (78.8%)	.088
Gender	Female	11 (37.9%)	21 (21.2%)
Race	Han	14 (48.3%)	70 (70.7%)	.044^b
Race	Other	15 (51.7%)	29 (29.3%)
NYHA grade	I	23 (79.3%)	81 (81.8%)	.789
NYHA grade	II	6 (20.7%)	18 (18.2%)
ASA grade	II	21 (72.4%)	84 (84.8%)	.167
ASA grade	III	8 (27.6%)	15 (15.2%)
BMI, kg/m²		24.2 (23.1, 30.2)	22.7 (22.1, 25.1)	<.001^b
Obesity, BMI >30 kg/m²		8 (27.6%)	7 (7.1%)	.006^b
Smoking		17 (58.6%)	58 (58.6%)	1.000
Hypertension		11 (37.9%)	37 (37.4%)	1.000
Diabetes mellitus		11 (37.9%)	8 (8.1%)	<.001^b
History of coronary stenting or CABG		14 (48.3%)	16 (16.2%)	.001^b
Hemoglobin, g/L		114.0 (110.0, 124.0)	123.0 (112.0, 132.0)	.055
Platelet count, 10⁹/mL		154.0 (145.0, 165.0)	154.0 (143.0, 167.0)	.376
LVEF, %		57.7 (56.6, 61.5)	57.5 (55.6, 60.1)	.436
Surgery time, minutes		150.0 (120.0, 165.0)	120.0 (120.0, 135.0)	<.001^b
Bleeding, mL		340.0 (290.0, 357.0)	345.0 (310.0, 360.0)	.875
Preoperative d-dimer, n/mL		569.0 (262.0, 938.0)	220.0 (165.0, 344.0)	<.001^b
Preoperative abnormal d-dimer		20 (69.0%)	30 (30.3%)	<.001^b
Preoperative TpP, mg/L		2.4 (2.4, 3.1)	2.7 (2.4, 2.9)	.861
Preoperative abnormal TpP		3 (10.3%)	0 (0.0%)	.011^b
Preoperative P-selectin, %		1.1 (0.5, 1.9)	0.4 (0.4, 0.5)	<.001^b
Preoperative abnormal P-selectin		10 (34.5%)	1 (1.0%)	<.001^b
Preoperative VWF, %		156.1 (138.5, 167.4)	106.5 (101.4, 132.1)	<.001^b
Preoperative abnormal VWF		19 (65.5%)	11 (11.1%)	<.001^b
Prethrombotic state		25 (86.2%)	37 (37.4%)	<.001^b

Abbreviations: NYHA grade, The New York Heart Association Functional Classification; ASA grade, American Society of Anesthesiologists physical status classification system; LVEF, left ventricular ejection fraction; TpP, thrombus precursor protein; VWF, von Willebrand factor; CABG, coronary artery bypass graft surgery; BMI, body mass index.

^aThe normal ranges of d-dimer, TpP, P-selectin, and VWF were 0 to 278 ng/mL, <5.5 mg/L, 0.2 to 1.4%, and 60% to 150%, respectively; the prethrombotic state was defined as any abnormal values observed in the 4 markers of d-dimer, TpP, P-selectin, and VWF at preoperation.

^bIndicates a significant difference between the patients with and without adverse cardiac events. Continuous data were presented as median (25th percentile, 75th percentile); categorical data were presented as count (percentage).

Association Between PTS and Adverse Cardiac Events

The preoperative levels of the d-dimer, P-selectin, and VWF were higher in the patients with adverse cardiac events than in those without adverse cardiac events, 569.0 versus 220.0 n/mL for d-dimer (P < .001), 1.1% versus 0.4% for P-selectin (P < .001), and 156.1% versus 106.5% for VWF (P < .001). And the percentages of patients with abnormal values for 1 of the 4 markers, that is, in d-dimer, P-selectin, TpP, or VWF, were also significantly higher in those with adverse cardiac events than in those without adverse cardiac events, 69.0% versus 30.3% for d-dimer, 10.3% versus 0% for TpP, 34.5% versus 1.0% for P-selectin, and 65.5% versus 11.1% for VWF (all P <.001). In addition, a significantly higher percentage of patients with the PTS was observed in those who had adverse cardiac events than in those without adverse cardiac events (86.2% vs 37.4%, P < .001; Table 1).

Risk Factors For Adverse Cardiac Events

In the univariate analysis, race, obesity, diabetes mellitus, heart disease, surgery time, and abnormal preoperation d-dimer, P-selectin, and VWF levels were significantly associated with adverse cardiac events. Although more patients with cardiac events than without cardiac events had abnormal TpP, an OR for TpP could not be obtained.

In multivariate model I, 6 variables were included (gender, diabetes mellitus, surgery time, and preoperation d-dimer, P-selectin, and VWF). After controlling for the other 5 variables, females had significantly higher risk of incurring adverse cardiac events than males (OR = 38.75, P < .001); patients with a history of diabetes mellitus were more likely to incur adverse cardiac events than those without diabetes mellitus history (OR = 236.76, P < .001); the risk of occurrence of adverse cardiac events was increased every minute by increase in the surgery time (OR = 1.06, P = .030); and those with abnormal preoperative values of P-selectin (OR = 23.52, P = .040) or VWF (OR = 25.71, P = .003) were more likely to have adverse cardiac events.

In multivariate model II, 5 variables were included (gender, obesity, diabetes mellitus, surgery time, and PTS). After controlling for the other 4 variables, females had a significantly higher risk of incurring adverse cardiac events than males (OR = 40.68, P = .002); patients with the history of diabetes mellitus were more likely to incur adverse cardiac events (OR = 402.80, P < .001); the risk of occurrence of adverse cardiac events was increased every minute by increase in the surgery time (OR = 1.09, P < .001); and those with PTS were more likely to experience adverse cardiac events (OR = 64.32, P < .001; Table 2).

Table 2.

Summary Risk Factors for Adverse Cardiac Events.^a

		Univariate Models		Multivariate Model I		Multivariate Model II
		Odds Ratio (95% CI)	P Value	Odds Ratio (95% CI)	P Value	Odds Ratio (95% CI)	P Value
Age, years		1.06 (0.98, 1.15)	.134
Gender	Female	2.27 (0.93, 5.54)	.072	38.75 (2.60, 577.48)	.008^b	40.68 (4.07, 406.87)	.002^b
Gender	Male	Reference		Reference		Reference
Race	Other	2.59 (1.11, 6.03)	.028^b
Race	Han	Reference
NYHA grade	I	1.17 (0.42, 3.30)	.761
NYHA grade	II	Reference
ASA grade	II	2.13 (0.80, 5.70)	.131
ASA grade	III	Reference
Obesity, BMI >30 kg/m²		5.01 (1.63, 15.34)	.005^b			7.43 (0.75, 73.87)	.087
Smoking		1.001 (0.43, 2.32)	.997
Hypertension		1.02 (0.44, 2.40)	.957
Diabetes mellitus		6.95 (2.45, 19.70)	<.001^b	236.76 (15.32, 3,660.11)	<.001^b	402.80 (21.61, 7,507.91)	<.001^b
Heart disease		4.84 (1.96, 11.95)	.001^b
Hemoglobin, g/L		0.97 (0.94, 1.01)	.139
Platelet count, 109/mL		1.01 (0.99, 1.03)	.408
LVEF, %		1.03 (0.90, 1.18)	.666
Surgery time, minutes		1.04 (1.02, 1.06)	<.001^b	1.06 (1.01, 1.12)	.030^b	1.09 (1.04, 1.15)	<.001^b
Bleeding, mL		0.999 (0.989, 1.008)	.810
Preoperative abnormal d-dimer		5.11 (2.09, 12.52)	<.001^b	5.49 (0.90, 33.43)	.065
Preoperative abnormal TpP		NA
Preoperative abnormal P-selectin		51.58 (6.23, 426.94)	<.001^b	23.52 (1.16, 477.38)	.040^b
Preoperative abnormal VWF		15.20 (5.65, 40.89)	<.001^b	25.71 (3.11, 212.84)	.003^b
Prethrombotic state (PTS)		10.47 (3.38, 32.46)	<.001^b			64.32 (6.36, 650.04)	<.001^b

Abbreviations: NYHA grade, The New York Heart Association Functional Classification; ASA grade, American Society of Anesthesiologists physical status classification system; LVEF, left ventricular ejection fraction; TpP, thrombus precursor protein; VWF, von Willebrand factor; BMI, body mass index; CI, confidence interval; NA, not available.

^aThe normal ranges of d-dimer, TpP, P-selectin, and VWF were 0 to 278 ng/mL, <5.5 mg/L, 0.2% to 1.4%, and 60% to 150%, respectively; the prethrombotic state was defined as any abnormal values observed in the 4 markers of d-dimer, TpP, P-selectin, and VWF at preoperation. NA indicates the OR was not available due to zero count. Model I: preoperation abnormal d-dimer, P-selectin, VWF, and the other variables with P value <.1 in the univariate analysis (gender, race, obesity, diabetes mellitus, heart disease, and surgery time) were stepwise entered into the model. Model II: prethrombotic state and the other variables with P value <.1 in the univariate analysis (gender, race, obesity, diabetes mellitus, heart disease, and surgery time) were stepwise entered into the model.

^bIndicates the corresponding variable had significant impact on the occurrence of adverse cardiac events.

Trends of PTS-Related Markers in the Perioperative Period

d -Dimer

In the adverse cardiac event group, d-dimer level was significantly increased from 569.0 ng/mL presurgically to 1252.0, 1352.0, and 1367.0 ng/mL in 24, 48, and 72 hours after the operation, respectively. In addition, d-dimer levels in those with adverse cardiac events were significantly higher than in those without adverse cardiac events in the 4 time points of the perioperative period.

TpP

In adverse cardiac event group, TpP levels were significantly increased from 2.37 mg/L preoperatively to 3.19 mg/L 24 hours after the operation and were significantly higher than the 2.59 mg/L in those without adverse cardiac events. In those without adverse cardiac events, no significant change was observed in TpP in the 4 time points of the perioperative period.

P-selectin

A significant increase in P-selectin with time was observed in both the groups (P < .001), and a higher slope for this increase was seen in the adverse cardiac event group. In the adverse event group, P-selectin levels were significantly increased from 1.1% at preoperation to 1.8%, 2.1%, and 2.4% in 24, 48, and 72 hours after the operation, respectively. P-selectin levels in those with adverse cardiac events were significantly higher than in those without adverse cardiac events in the 4 time points of the perioperative period (P < .001).

VWF

A smooth increase in VWF with time was also observed in both the groups. The VWF levels in those with adverse cardiac events were significantly higher than in those without adverse cardiac events at each of the 4 time points of perioperative period (P < .001; Figure 1).

Figure 1.

Summary for the trends of d-dimer (A), thrombus precursor protein (B), P-selectin (C), and von Willebrand factor (D) in the perioperative period. Data were presented as median (25th percentile, 75th percentile). *Indicates a significant difference when compared to preoperation. ^†Indicates a significant difference when compared to 24 hours postoperation. ^‡Indicates a significant difference when compared to 48 hours postoperation. ^§Indicates a significant difference between the patients with and without adverse cardiac events.

Discussion

A number of studies have shown that PTS plays a crucial role in the development of atherosclerosis and ischemic heart disease.^2,3 In the present study, preoperative TpP, P-selectin, d-dimer, and VWF were used as markers for PTS and their elevation was used to determine its presence. Using this criterion, our results showed 48.4% of patients to have PTS (most had increased levels of d-dimer, the marker of fibrin degradation). However, preoperative tests showed normal coagulation in these patients. These data suggest that PTS is common in patients with CHD and that routine laboratory tests of coagulation cannot be used to determine its presence. In clinical practice, clinicians usually pay attention to perioperative screening for bleeding tendency and often neglect consideration of PTS, an abnormal coagulation state. But patients with PTS are susceptible to thrombosis and theoretically to adverse cardiac events. And in patients with CHD receiving noncardiac surgery, adverse cardiac events are the main cause of perioperative death.⁴ Therefore, it is imperative to explore the correlation between PTS and adverse cardiac events.

Plasma d-dimer is a fibrin degradation product that has been used as a marker for thrombosis and secondary fibrinolysis and whose elevation suggests PTS. In addition, the degradation product of plasma d-dimer is a specific substance activating platelets.⁵ P-selectin is the most specific marker for activation and release of platelets, plays a pivotal role in the initiation and amplification of thrombosis,⁶ and is also used to determine PTS in patients with CHD. A large-scale study has reported that patients with P-selectin elevation have increased risk of adverse cardiac events compared to those with normal P-selectin levels,⁷ a result consistent with our findings. The TpP refers to the soluble fibrin polymer and is the direct precursor of insoluble fibrin in the thrombi. The TpP level reflects the activity of circulating thrombin, which is a sensitive indicator before thrombosis and has been used as a marker for imminent thrombosis. Studies have demonstrated that TpP has high sensitivity and specificity in the determination of PTS.⁸ Thus, TpP has an advantage in the early diagnosis of myocardial infarction. Our results consistently indicated an elevation of perioperative TpP level. The VWF, a marker of endothelial damage or dysfunction, is a carrier for procoagulant factor VIII and increases platelet adhesion to damaged tissue.⁹

Presurgery elevation of d-dimer was the most frequently found of the 4 markers and was seen in 39.1% of the patients (n = 50). Elevations of VWF and P-selectin were the second and the third most frequently found and were noted in 23.4% and 8.6% of patients, respectively. Only 2.3% of the patients had a presurgery elevation in TpP (n = 3). Although studies show that TpP, P-selectin, VWF, and d-dimer can be used as markers for PTS, these markers did not simultaneously become elevated in patients with CHD due to the difference in the times of formation of the 4 markers. P-selectin, d-dimer, VWF, and TpP levels reflect the coagulation state of the platelet coagulation–fibrinolysis system, and these markers may interact with each other leading to a vicious circle and subsequent PTS. Elevations of P-selectin, d-dimer, and VWF have value as predictors of adverse cardiac events, but P-selectin, d-dimer, or VWF alone have low sensitivity and specificity. Thus, the use of 3 markers, or these markers in combination with other risk factors, is required to increase the ability to predict adverse cardiac events, a result consistent with the findings in a recent study of Korkeila et al.¹⁰ Our results also showed that the levels of TpP, P-selectin, d-dimer, and VWF increased to different extents in the 3 days after surgery, an increase that may be attributed to the initiation of coagulation due to surgical and tissue injury.

The incidence of adverse cardiac events in our study was dramatically higher than that previously reported in patients with CHD receiving noncardiac surgery (1%-5%). In addition, 86.2% of the patients developed adverse cardiac events had PTS, which was significantly higher than 37.4% in nonadverse cardiac event participants (P < .001). This suggests PTS is highly correlated with adverse cardiac events and that the markers for PTS are positively associated with adverse cardiac events. Thus, we speculate that PTS in patients with coronary atherosclerosis may be an important precipitating cause of adverse cardiac events.

To date, in the American College of Cardiology/American heart Association Guideline (2007) for patients with CHD receiving noncardiac surgery¹¹ and in the European Guideline (2009),¹² PTS is not addressed. Our results showed that PTS is an independent risk factor for adverse cardiac events and is closely related to perioperative adverse cardiac events. Multivariate logistic regression analysis showed PTS to have an OR of 64.32 (P < .001) for adverse cardiac events. Thus, PTS may be an important trigger factor and should be considered in the preoperative evaluation.

This study has several limitations. It was a single, not a multicenter study. The PTS is a pathological condition involving many factors, and we made no investigation of its etiology. And there are many markers for PTS, but in this study we focused only on the 4 representative markers. In our multivariate analysis, in addition to PTS, female gender and diabetes were robust and independent predictors of perioperative cardiac events. One unanswered question is the respective sensitivity and selectivity of the 3 predictors and what improvement in prediction of risk could be obtained by using them together.

In conclusion, preoperative PTS is an independent risk factor for perioperative events in patients with CHD undergoing noncardiac surgery, and its clinical use in preoperative evaluation might enable better regulation of postoperative coagulation state and decrease the incidence of perioperative adverse cardiac effects. Our findings may provide evidence supporting the use of evaluation of risk factors in prediction of perioperative adverse cardiac events and for regulation of the perioperative coagulation state.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: key mandatory plan of project of supporting Xinxiang with science and technology (No: 200991126).

References

Mannucci

Giangrande

. Detection of the prethrombotic state due to procoagulant imbalance. Eur J Haematol. 1992;48(2):65–69.

Smid

Dielis

Winkers

. Thrombin generation in patients with a first acute myocardial infarction. J Thromb Haemost. 2011;9(3):450–456.

Merlini

Bauer

Oltrona

. Persistent activation of coagulation mechanism in unstable angina and myocardial infarction. Circulation. 1994;90(1):61–68.

Mangano

Goldman

. Preoperative assessment of patients with known or suspected coronary disease. N Eng J Med. 1995;333(26):1750–1756.

Wada

Sakuragawa

. Are fibrin-related markers useful for the diagnosis of thrombosis? Semin Thromb Hemost. 2008;34(1):33–38.

Chelliah

Lucking

Tattersall

. P-selectin antagonism reduces thrombus formation in humans. J Thromb Haemost. 2009;7(11):1915–1919.

Ridker

Buring

Rifai

. Soluble P-selectin and the risk of future cardiovascular events. Circulation. 2001;103(4):491–495.

Kozlova

. The prognostic value of thrombus precursor in the assessment of the probability for venous thrombosis recurrence after the completion of anticoagulatory therapy with warfarin. Kin Med (Mosk). 2006;84(12):51–53.

Ruggeri

, Ware J. von Willebrand factor. FASEB J. 1993;7(2):308–316.

10.

Korkeila

Mustonen

Koistinen

. Clinical and laboratory risk factors of thrombotic complications after pacemaker implantation: a prospective study. Europace. 2010;12(6):817–824.

11.

Fleisher

Beckman

Brown

. ACC/AHA 2007 Guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery. J Am Coll Cardiol. 2007;50(17):1707–1732.

12.

Poldermans

Bax

Boersma

. Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery. Eur Heart J. 2009;30(22):2769–2812.

Prethrombotic State and Cardiac Events in Patients With Coronary Heart Disease During Noncardiac Surgery