Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Open Access

Peer-reviewed

Research Article

Prognostic value of hematological parameters in patients with acute myocardial infarction: Intrahospital outcomes

Abstract

Background

The intensity of the inflammatory response and hemodynamic repercussion in acute myocardial infarction causing the presence in the peripheral circulation of nucleated red blood cells (NRBCs), increases in mean platelet volume (MPV) and neutrophil to lymphocyte ratio (NLR) are associated with a poorer prognosis. The aim of this study was to assess the role of these hematological biomarkers as predictors of all causes of mortality during the hospitalization of patients with acute myocardial infarction.

Methods

Nucleated red blood cells, mean platelet volume and neutrophil to lymphocyte ratio were measured daily during the hospitalization of the patients with acute myocardial infarction. We excluded patients younger than 18 years, on glucocorticoid therapy, with cancer or hematological diseases and those that were readmitted after hospital discharge. We performed a multiple logistic analysis to identify independent predictors of mortality.

Results

We included 466 patients (mean age 64.2 ± 12.8 years, 61.6% male). The prevalence of NRBCs in the sample was 9.1% (42 patients), with levels > 200/μL in 27 patients (5.8%). The mean MPV value was 10.9 ±0,9 and the mean NLR value was 3.71 (2,38; 5,72). In a multivariate analysis of serum NRBCs (HR 2.42, 95% CI: 1.35–4.36, p = 0.003), MPV (HR 2.97, 95% CI: 1.15–7.67, p = 0.024) and NLR (HR 5.02, 95% CI: 1.68–15.0, p = 0.004). The presence in the peripheral blood of NRBCs, increased in mean platelet volume and neutrophil to lymphocyte ratio were associated with higher mortality.

Conclusions

Nucleated red blood cells, mean platelet volume and neutrophil to lymphocyte ratio are independent predictors of intrahospital mortality. Therefore, an important tool in intrahospital clinical surveillance.

Citation: Monteiro Júnior JGdM, Torres DdOC, da Silva MCFC, Martins CMdH, da Silva IK, do Nascimento MEM, et al. (2018) Prognostic value of hematological parameters in patients with acute myocardial infarction: Intrahospital outcomes. PLoS ONE 13(4): e0194897. https://doi.org/10.1371/journal.pone.0194897

Editor: Katriina Aalto-Setala, University of Tampere, FINLAND

Received: January 4, 2018; Accepted: March 12, 2018; Published: April 18, 2018

Copyright: © 2018 Monteiro Júnior et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: The authors received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Abbreviations: AMI, acute myocardial infarction; CRP, C-reactive protein; HR, hazard ratio; IG, Immature granulocytes; KILLIP score, risk of in-hospital death proposed by Killip and. Kimball; MPV, mean platelet volume; NLR, neutrophil to lymphocyte ratio; NRBCs, nucleated red blood cells; PDW, platelet distribution width; PROCAPE, Pernambuco Cardiac Emergency Hospital; RDW, red cell distribution width; ROC, receiver operating characteristic; STEMI, with ST elevation myocardial infarction; Non-STEMI, with non-ST elevation myocardial infarction; TIMI risk, thrombolysis in myocardial infarction risk; TNT, troponin T; WBC, white blood cell count

Introduction

Acute myocardial infarction (AMI) is a frequent emergency in the world, with great potential for morbidity and mortality despite all advances in treatment in the last three decades [1]. It is an essentially inflammatory disease and, depends on the extent of cardiac damage, with hemodynamic repercussion. These inflammatory and hypoxemic processes have been associated with the presence of hematological markers in the peripheral blood owing to the high concentrations of erythropoietin, interleukin-3 and interleukin-6 caused by local or systemic disorders in critical cardiac patients [2].

Researches have shown that there is an increase in myeloid activity in AMI and it has arisen strong interest in hematological parameters, given that they may provide independent information on pathophysiology and risk stratification [3]. Therefore, the study of the complete blood count is of great importance in the acute coronary syndrome with, for examples, red cell distribution width (RDW) is a measure of variations in the volume of red blood cells and it is an essential predictor of severity coronary artery disease among patients with AMI [4,5], white blood cell count (WBC) elevated was found to be a relevant death risk factor during the first 30 days and 6 months following the myocardial infarction [6] and platelet distribution width (PDW) indicates a varied size of platelets and it also serves as a useful prognostic factor for long-term mortality in patients after AMI [7,8]. Mean platelet volume (MPV) is an indicator of platelet size and activation marker [9–15]. In the recent years, numerous papers have been published regarding the value of platelet to lymphocyte ratio (PLR) [16–19], mean platelet volume to lymphocyte ratio (MPVLR) [20,21] and neutrophil to lymphocyte ratio (NLR) [22–36] in predicting short and long-term mortality in patients with ST-elevation (STEMI) and with non-ST elevation (non-STEMI). The lymphocyte count is inversely association with inflammation and, low lymphocyte count is a poorer prognostic marker in patients with AMI [37].

Nucleated red blood cells (NRBCs) are immature erythrocyte cells present in the bone marrow in the process of hematopoiesis. In healthy adult, there aren’t NRBCs in the peripheral blood. Prior studies have shown that severe hypoxemia or inflammation are responsible for the presence of NRBCs in peripheral blood, when hematological and oncological diseases are excluded. Therefore, the presence of NRBCs in the peripheral circulation are associated with poorer prognosis [38–40]. The scientific evidences have demonstrated the value of this variable with importance tool in the intrahospital surveillance.

In this study, despite of the diversity of hematological variables, all components of the hemogram were represented: NRBCs (red blood cells), NLR (white blood cells) and MPV (platelets). Therefore, the aim of this study was to assess the role of these hematological biomarkers as predictors of all causes of mortality during the hospitalization of patients with acute myocardial infarction.

Materials and methods

Subjects and protocol

This study was approved by the Research Ethics Committee in the HOSPITAL COMPLEX HUOC/PROCAPE of the University of Pernambuco under number CAAE: 51802115.7.0000.5192 (Brazil Plataform). All consecutive patients admitted with acute myocardial infarction to the Pernambuco Cardiac Emergency Unit (PROCAPE), a specialized tertiary care cardiovascular teaching hospital with 250 beds, between January 2016 and September 2016 were included in the research. We excluded patients younger than 18 years, on glucocorticoid therapy, with câncer or hematological diseases and those that were readmitted after hospital discharge. All patients included in the study signed a free and informed consent form.

The diagnosis of acute myocardial infarction was given by clinical history, electrocardiography and laboratory abnormality (troponin). After the diagnosis was confirmed, the patient or family member answered about risk factors. He was simply asked if he was taking any medication for high blood pressure, diabetes mellitus, dyslipidemia and depression. Patient with arterial blood pressure measurements above 140/90 mmHg was considered hypertensive and fasting plasma glicose above 126 mg/dL was considered diabetes mellitus. He was also asked about sedentary lifestyle, smoking, kidney disease, and family history of coronary artery disease. Then, this patient would follow the protocol of the institution until discharge but, only suggested in a previous communication to the medical staff of the hospital, the request for a daily blood count.

In the first twenty-four hours of the admission, the patients were classified in the AMI with ST segment elevation (STEMI)) and AMI without ST segment elevation(non-STEMI), and their respective Killip and TIMI Risk risk scores were calculated.

Laboratory tests

Blood samples were obtained daily in the morning until discharge from the hospital. Complete blood count parameters including NRBCs, leukocytes, neutrophils, lymphocyte, platelet, MPV were measured using a Sysmex XE-2100 blood analyzer (Sysmex, Kobe, Japan) [41,42]. The troponin samples, as well as other biochemical measurements and electrolyte levels, were measured using a Roche Cobas Integra 400 analizer with a reference value of 0.014 μg / L.

A positive NRBC was defined as any value above zero, high MPV cut-off level is ≥10.4 fL and NLR was calculet by dividing the neutrophil count with the lymphocyte count with high cut-off level is ≥ 3.7.

Statistical analysis

Contínuos variables were expressed as mean ± standard deviation or median and quartiles, as appropriated analyze. Categorical variables were presented as absolute values and percents. Categorical variables were compared using two-tailed Pearson’s chi-squared (X2) test with the Yates correlation or Fisher’s exact test. The comparison of means, to establish the normality of the distribution, was carried out using the Kolmogov-Smirnov test, followed by Student’s t test for normal distribution variables or Mann-Whitney’s non-parametric test form non-normal distribution variables. The relative mortality risk was calculated for clinical and laboratory variables, with confidence intervals of 95%. Logistic univariate regressions were performed to evaluate predictors of mortality of these variables. A multivariate logistic regression model was used to identify independent predictors of mortality. Variables with p <0.05 on univariate analysis were entered a multivariate analysis. Due to the highly skewed distribution of the NRBC, we chose to perform its analysis as a binary variable based on the presence or absence of NRBC in the peripheral blood.

The level of statistical significance adopted was p < 0.05. Sample size was calculated to assess a mortality Hazard Ratio between patients with AMI and NRBCs, MPV and NLR of according to previous study, assuming an α-error of 5% and a statistical power of 95%. The minimum sample size was 170 patients. Statistical analyses were conducted using the Statistical Program for Social Sciences (SPSS), version 10.0 for Windows.

Results

A total of 549 patients initially screened, of whom 83 were excluded as shown in Fig 1. There were no follow-up losses and the final sample comprised 466 patients (mean age 64.2 ± 12.8 years, 61.6% male) and AMI with STEMI (70%). The demographic, clinical and laboratory characteristics of the study patients are described in Table 1. A total of 27 cardiac surgeries (5.8%), 226 coronary angioplasties (48.5%) were performed during hospitalization of these patients. Among all patients, 32 (6.9%) had used antibiotic therapy. The total mortality of the study was 11.8% (55 patients).

thumbnail
Download:
Fig 1. Flowchart of patients.

https://doi.org/10.1371/journal.pone.0194897.g001

thumbnail
Download:
Table 1. Characteristics of patients with acute myocardial infarction.

https://doi.org/10.1371/journal.pone.0194897.t001

The presence of NRBCs in the sample was 9.1% (42 patients), with levels > 200/μL in 27 patients (5.8%). The mean MPV value was 10.9 ±0,9 and the mean NLR value was 3.71 (2,38; 5,72) (Table 1). The intrahospital mortality is associated with presence of NRBCs in peripherical blood and increases in mean MPV and NLR (Fig 2).

thumbnail
Download:
Fig 2.

a. Nucleated red blood cells, b. Mean platelet volume, c. Neutrophil to lymphocyte ratio and intrahospital mortality.

https://doi.org/10.1371/journal.pone.0194897.g002

The factors associated with intrahospital mortality in this study are the age (HR 2.52, 95% CI: 1.37–6.65, p = 0.003), NRBC (HR 5.65, 95% IC: 3.23–9.88, p<0.001), MPV (HR 4.46, 95% IC: 1.78–11.2, p = 0.001) and NLR (HR 11.3, 95% IC: 4.06–31.2, p = 0.000). The age among the demographic characteristics is significantly associated with mortality (HR 2.52, 95% CI: 1.37–6.65, p = 0.003). However, in this sample there is an inverse association with family history (HR 0.35, 95% CI: 0.19–0.67, p = 0.002) (Table 2).

thumbnail
Download:
Table 2. Factors related to intrahospital mortality among patients with acute myocardial infarction.

https://doi.org/10.1371/journal.pone.0194897.t002

After adjustment, multivariate analysis of the factors associated with intrahospital mortality among patients with acute myocardial infarction as described in Table 3. The survival curve of intrahospital mortality is shown in Fig 3.

thumbnail
Download:
Fig 3. Kaplan-Meyer curve of intrahospital mortality.

https://doi.org/10.1371/journal.pone.0194897.g003

thumbnail
Download:
Table 3. Multivariate analysis of factors related to intrahospital mortality among patients with acute myocardial infarction.

https://doi.org/10.1371/journal.pone.0194897.t003

Discussion

In this study, the main finding was that the daily quantifications of NRBCs, MPV and NLR are important to the prognosis in intrahospital patients with AMI. These variables reflect the severity of systemic impairment and consequently on clinical outcome at each moment, depending on the response to the proposed treatment. It is linked to an increased myeloid activity, inducing the release of hematopoietic stem cells from bone marrow niches and causing the further systemic stimulation of atherosclerotic plaques [3]. However, there are also other co-morbidities that may contribute to the clinical state and consequently the time of intrahospital stay and mortality. Therefore, the intensity of inflammation and hypoxemia of multifactorial origin during the hospitalization of these patients causes this hematopoietic feedback.

The presence of NRBCs in peripheral blood in patients with AMI, as demonstrated in this study, are associated with mortality (HR 2.42, 95% CI: 1.35–4.36, p = 0.003). These findings are in accordance with recent published papers, although in difference populations. Stachon et al. [38] studied this variable in the intensive care unit and their conclusion were this parameter may serve as a daily indicator of patients at high mortality risk and they should not be relocated to a normal ward while remaining NRBC-positive. Desai et al. [39] associated NRBC-positive with a higher mortality rate in patients with surgical sepsis (27% vs 12%, p = 0.007). Kurt et al. [40] associated the NRBCs with arterial oxygen partial tension (prior to the initial detection of NRBCs in the peripheral blood, pO2 levels were significantly lower in patients who died than in surviving patients).

In this same inflammatory and hypoxemic context due to several etiological factors, as observed in the present study, the increased MPV are also associated with mortality in patients with AMI (HR 2.97, 95% CI: 1.15–7.67, p = 0.024). Previous papers share the information that the larger platelets are metabolically and enzymatically more active than small platelets and are reflected by elevation in MPV [12,13]. Therefore, these biological variables that determine important role in the development of intravascular thrombus [11]. Hilal et al. [9] employed the same cut-off value of 10.4 in their paper in which they demonstrated that MPV ≥ 10.4 is a predictor of severe atherosclerosis with sensibility of 39% ans specificity of 90% (ROC curve: 0.631, 95% CI: 0.549–0.708, p = 0.003).

The blood count is performed on admission and daily routinely and carries important prognosis information. Our findings in this study met high association between NLR and intrahospital mortality in patients with AMI (HR 11.3, 95% CI: 4.06–31.2), p = 0.000). Studies have shown that the NLR is a strong predictor of short and long-term mortality in stable and unstable coronary insufficiency [22]. It is relationship with the inflammation, which participates articulately in all stages, from beginning of the lesion to the progression and destabilization of the plaque [35]. There are studies comparing NLR with SYNTAX score which evaluated the severity coronary angiographic, with GRACE, KILLY and TIMI risk scores which evaluated demographic data and variables that determine the intrahospital death in patients with AMI [24,28]. Therefore, NLR may be used as cost-effective predictors of inflammation and AMI complications.

The selection of patients from single center may raise a limitation. However, we sought to increase the sample to minimize possible biases and confounding factors in the study.

Conclusion

The survival rate of patients with acute myocardial infarction decreases after hospital stay due to several complications that may occur during this period. Therefore, objective monitoring tools are needed.

Nucleated red blood cells, mean platelet volume and neutrophil to lymphocyte ratio are independent markers of death, express the degree of systemic inflammation and hypoxemic impairment, which are the major pathophysiological mechanisms of diseases. Therefore, an important tool in intrahospital clinical surveillance. However, more research on these hematological biomarkers and dissemination of knowledge in the daily practice of the multiprofessional hospital team are necessary.

Supporting information

S1 Table. Characteristics of patients with acute myocardial infarction.

https://doi.org/10.1371/journal.pone.0194897.s001

(PDF)

S2 Table. Factors related to intrahospital mortality among patients with acute myocardial infarction.

https://doi.org/10.1371/journal.pone.0194897.s002

(PDF)

S3 Table. Multivariate analysis of factors related to intrahospital mortality among patients with acute myocardial infarction.

https://doi.org/10.1371/journal.pone.0194897.s003

(PDF)

S1 Database.

https://doi.org/10.1371/journal.pone.0194897.s004

(XLS)

References

  1. 1. Anderson JL, Morrow DA. Acute Myocardial Infarction. N Engl J Med. 2017 May 25; 376(21): 2053–2064. pmid:28538121
  2. 2. Monteiro Júnior JGM, Torres DOC, Silva MCFC, Ramos TMB, Alves ML, Filho WJN, et al. Nucleated red blood cells as predictors of all-cause mortality in cardiac intensive care unit patients: a prospective cohort study. Plos One 2015 Dec; 10(12): e0144259. pmid:26713613
  3. 3. Budziannowski J, Pieszko K, Burchardt P, Rzezniczak J, and Hiczkiewicz J. The Role of Hematological Indices in Patients with Acute Coronary Syndrome. Dis Markers. 2017; 2017:3041565. pmid:29109595
  4. 4. Akin F, Köse N, Ayça B, Katkat F, Duran M, Uysal OK, Arinc H. Relation between red cell distribution width and severity of coronary artery disease in patients with acute myocardial infarction. Angiology. 2013 Nov;64(8):592–6. pmid:23070683
  5. 5. Acet H, Ertaş F, Akıl MA, Özyurtlu F, Polat N, Bilik MZ, et al. Relationship Between Hematologic Indices and Global Registry of Acute Coronary Events Risk Score in Patients With ST-Segment Elevation Myocardial Infarction. Clin Appl Thromb Hemost. 2016 Jan; 22(1):60–8. pmid:24816530
  6. 6. Sabatine MS, Morrow DA, Cannon CP, Murphy SA, Demopoulos LA, DiBattise PM, et al. Relationship between baseline white blood cell count and degree of coronary artery disease and mortality in patients with acute coronary syndromes. J Am Coll Cardiol. 2002 Nov 20;40(10):1761–8. pmid:12446059
  7. 7. Bekler A, Ozkan MT, Tenekecioglu E, Gazi E, Yener AU, Temiz A, et al. Increased Platelet Distribution Width is Associated with Severity of Coronary Artery Disease in Patients with Acute Coronary Syndrome. Angiology 2015 Aug; 66(7): 638–43. pmid:25112777
  8. 8. Rechciński T, Jasińska A, Foryś J, Krzemińska-Pakuła M, Wierzbowska-Drabik K, Plewka M, et al. Prognostic value of platelet indices after acute myocardial infarction treated with primary percutaneous coronary intervention. Cardiol J. 2013;20(5):491–8. pmid:24469872
  9. 9. Uysal HB, Dagli B, Akgullu C, Avcil M, Zencir C, Ayhan M, et al. Blood Count Parameteres Can Predict the Severity of Coronary Artery Disease. Korean J Intern Med. 2016; 31: 1093–1100. pmid:27052265
  10. 10. Taskesen T, Sekhon H, Wroblewski I, Goldfarb M, Ahmad MB, Nguyen QT, et al. Usefulness of Mean Platelet Volume to Predict Significant Coronary Artery Disease in Patients With Non-ST-Elevation Acute Coronary Syndromes. Am J Cardiol. 2017 Jan 15;119(2):192–196. pmid:27814786
  11. 11. Larsen SB, Grove EL, Hvas AM, Kristensen SD. Platelet turnover in stable coronary artery disease–influence of thrombopoietin and low-grade inflamation. Plos One 2014; 9(1): e85566. pmid:24465602
  12. 12. Dehghani MR, Taghipour-Sani L, Rezaei Y, Rostani R. Diagnostic importance of admission platelet volume indices in patients with acute chest pain suggesting acute coronary syndrome. Indian Heart J. 2014 Nov-Dec;66(6):622–8. pmid:25634396
  13. 13. Murat SN, Duran M, Kalay N, Gunebakmaz O, Akpek M, Doger C, et al. Relation Between Mean Platelet Volume and Severity of Atherosclerosis in Patients with Acute Coronary Syndromes. Angiology 2013 Feb;64(2):131–6. pmid:22334878
  14. 14. Kalay N, Dogdu O, Koc F, Yarlioglues M, Ardic I, Akpek M, et al. Hematologic parameters and angiographic progression of coronary atherosclerosis. Angiology 2012 Apr; 63 (3): 213–7. pmid:21733954
  15. 15. Klovaite J, Benn M, Yazdanyar S, Nordestgaard BG. High platelet volume and increased risk of myocardial infarction: 39 531 participants from the general population. J Thromb Haemost. 2011 Jan;9(1):49–56. pmid:20942852
  16. 16. Acet H, Ertaş F, Akıl MA, Özyurtlu F, Yıldız A, Polat N, et al. Novel predictors of infarct-related artery patency for ST-segment levation myocardial infarction: Platelet-to-lymphocyte ratio, uric acid, and neutrophil-to-lymphocyte ratio. Anatol J Cardiol. 2015 Aug;15(8):648–56. pmid:25550174
  17. 17. Ayça B, Akin F, Çelik Ö, Yüksel Y, Öztürk D, Tekiner F, et al. Platelet to lymphocyte ratio as a prognostic marker in primary percutaneous coronary intervencion. Platelets 2015; 26(7): 638–44. pmid:25350375
  18. 18. Kurtul A, Yarlioglues M, Murat SN, Ergun G, Duran M, Kasapkara HA et al. Usefulness of the Platelet-to-Lymphocyte Ratio in Predicting Angiographic Reflow After Primary Percutaneous Coronary Intervention in Patients With Acute ST-Segment Elevation Myocardial Infarction. Am J Cardiol. 2014 Aug 1;114(3):342–7. pmid:24948493
  19. 19. Kurtul A, Murat SN, Yarlioglues M, Duran M, Ergun G, Acikgoz SK, et al. Association of Platelet-to-Lymphocyte Ratio with Severity and Complexity of Coronary Artery Disease in Patients with Acute Coronary Syndromes. Am J Cardiol. 2014 Oct 1;114(7):972–8. pmid:25118117
  20. 20. Hudzik B, Szkodziński J, Lekston A, Gierlotka M, Poloński L, Gąsior M. Mean platelet volume-to-lymphocyte ratio: a novel marker of poor short- and long-term prognosis in patients with diabetes mellitus and acute myocardial infarction. Journal of Diabetes and Its Complications. 2016 Aug;30(6):1097–102. pmid:27138871
  21. 21. Kurtul A, Acikgoz SK. Usefulness of Mean Platelet Volume-to-Lymphocyte Ratio for Predicting Angiographic No-Reflow and Short-Term Prognosis After Primary Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction. Am J Cardiol. 2017 Aug 15;120(4):534–541. pmid:28633762
  22. 22. Azab B, Zaher M, Weiserbs KF, Torbey E, Lacossiere K, Gaddam S, et al. Usefulness of neutrophil to lymphocyte ratio in predicting short- and long-term mortality after non-ST elevation myocardial infarction. The American Journal of Cardiology 2010 Aug 15, 106 (4): 470–6. pmid:20691303
  23. 23. Yalcinkaya E, Yuksel C, Celik M, Kabul HK, Barcin C, Gokoglan Y, et al. Relationship between Neutrophil-to-Lymphocyte Ratio and Eletrocardiographyc Ischemia Grade in STEMI. Arq Bras de Cardiol. 2015 Feb; 104(2): 112–9. pmid:25424159
  24. 24. Kurtul S, Sarli B, Baktir AO, Demirbas M, Saglam H, Dogan Y, et al. Neutrophil to Lymphocyte Ratio Predicts SYNTAX Score in Patients With Non-ST Segment Elevation Myocardial Infarction. Int Heart J. 2015; 56(1):18–21. pmid:25742940
  25. 25. Gazi E, Bayram B, Gazi S, Temiz A, Kirilmaz B, Altun B, et al. Prognostic Value of the Neutrophil-Lymphocyte Ratio in Patients with ST-Elevated Acute Myocardial Infarction. Clin Appl Thromb Hemost. 2015 Mar; 21(2):155–9. pmid:23754837
  26. 26. Zhang GY, Chen M, Yu ZM, Wang XD, Wang ZQ. Relation between neutrophil-to-lymphocyte ratio and severity of coronary artery stenosis. Genet. Mol. Res. 2014 Nov 11;13(4):9382–9. pmid:25501149
  27. 27. Verdoia M, Barbieri L, Di Giovine G, Marino P, Suryapranata H, De Luca G, et al. Neutrophil to Lymphocyte Ratio and the Extent of coronary Artery Disease: Results From a Large Cohort Study. Angiology 2016 Jan; 67(1): 75–82. pmid:25818102
  28. 28. Oncel RC, Ucar M, Karakas MS, Akdemir B, Yanikoglu A, Gulcan AR et al. Relation of Neutrophil-to-Lymphocyte Ratio with GRACE Risk Score to In-Hospital Cardiac Events in Patients with ST-Segment Elevated Myocardial Infarction. Clin Appl Thromb Hemost. 2015 May;21(4):383–8. pmid:24078555
  29. 29. Soylu K, Gedikli Ö, Dagasan G, Aydin E, Aksan G, Nar G, et al. Neutrophil-to-lymphocyte ratio predicts coronary artery lesion complexity and mortality after non-ST-segment elevation acute coronary syndrome. Rev Port Cardiol. 2015 Jul-Aug;34(7–8):465–71. pmid:26164277
  30. 30. Bolca O, Güngör B, Özcan KS, Karadeniz FÖ, Sungur A, Köroğlu B, et al. The neutrophil-to-lymphocyte ratio is associated with bare-metal stent restenosis in STEMI patients treated with primary PCI. Coron Artery Dis. 2015 Aug; 26(5): 402–8. pmid:25919903
  31. 31. He J, Li J, Wang Y, Hao P, Hua Q. Neutrophil-to-lymphocyte ratio (NRL) predicts mortality and adverse-outcomes after ST-segment elevation myocardial infarction in Chinese people. Int J Clin Exp Pathol. 2014 Jun 15; 7(7): 4045–56. www.ijcep.com / ISSN: 1936-2625/IJCEP0000818. pmid:25120783
  32. 32. Williams BA, Merhige ME. Association between neutrophil-lymphocyte ratio and impaired myocardial perfusion in patients with known or suspected coronary disease. Heart Lung. 2013 Nov-Dec; 42(6): 436–41. pmid:23981470
  33. 33. Sahin DY, Elbasan Z, Gür M, Yildiz A, Akpinar O, Icen YK, et al. Neutrophil to lymphocyte ratio is associated with the severity of coronary artery disease in patients with ST-segment elevation myocardial infarction. Angiology. 2013 Aug; 64 (6): 423–9. pmid:22802534
  34. 34. Kaya H, Ertaş F, Soydinç MS, et al. Association Between Neutrophil to Lymphocyte Ratio and Severity of Coronary Artery Disease. Clin Appl Thromb Hemost. 2014 Mar; 20(2): 221. pmid:23925399
  35. 35. Choi YH, Hong YJ, Ahn Y, Park IH, Jeong MH. Relationship between Neutrophil-to-Lymphocyte Ratio and Plaque Components in Patients with Coronary Artery Disease: Virtual Histology Intravascular Ultrasound Analysis. J Korean Med Sci. 2014 Jul;29(7):950–6. pmid:25045227
  36. 36. Hartopo AB, Puspitawati I, Setianto BY. On-admission High Neutrophil to Lymphocyte Ratio as Predictor of In-hospital Adverse Cardiac Event in ST-elevation Myocardial Infarction. Acta Med Indones. 2015 Jan;47(1):3–10. pmid:25948761
  37. 37. Núñez J, Núñez E, Bodí V, Sanchis J, Mainar L, Miñana G et al. Low lymphocyte count in acute phase of ST-segment elevation myocardial infarction predicts long-term recurrent myovardial infarction. Coronary Artery Disease 2010 Jan; 21:1–7. pmid:20050312
  38. 38. Stachon A, Sebbers E, Holland-Letz T, Kempf R, Herinf S, Krieg M. Nucleated red blood cells in the blood of medical intensive care patients indicate increased mortality risk: a prospective cohort study. Critical Care 2007 Jun; 11: R62. pmid:17550592
  39. 39. Desai S, Jones SL, Turner KL, Hall J, Moore LJ. Nucleated red blood cells are associated with a higher mortality rate in patients with surgical sepsis. Surgical Infections 2012; 13 (6): 360–5. pmid:23237100
  40. 40. Kuert S, Holland-Letz T, Friese J, Stachon A. Association of nucleated red blood cells in blood and arterial oxygen partial tension. Clin Chem Lab Med 2011; 49 (2): 257–63. pmid:21118046
  41. 41. Nakul-Aquaronne D, Sudaka-Sammarcelli I, Ferrero-Vacher C, Starck B, Bayle J. Evaluation of the Sysmex Xe-2100 hematology analyzer in hospital use. Journal of Clinical Laboratory Analysis 2003; 17(4): 113–23. pmid:12784259.
  42. 42. Pipitone S, Pavesi F, Testa B, Bardi M, Peri GB, Gennari D, et al. Evaluation of automated nucleated red blood cells counting on Sysmex XE5000 and Siemens ADVIA 2120. Clin Chem Lab Med 2012 Oct 1; 50(10):1857–9. pmid:23089720