scholarly journals Dysregulation of Hemostatic Biomarkers, Inflammatory Biomarkers, and Alteration of Cellular Indices As Predictors of Adverse Outcomes in Pulmonary Embolism Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2408-2408
Author(s):  
Iman Darwish ◽  
Yevgeniy Brailovsky ◽  
Amir Darki ◽  
Debra Hoppensteadt ◽  
Brett Slajus ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Patient Outcomes ◽  
White Cell ◽  
Inflammatory Biomarkers ◽  
Positive Trend ◽  
Pronounced Increase ◽  
Lymphocyte Ratio ◽  
Cell Counts ◽  
All Cause Mortality ◽  
D Dimer

Background: Pulmonary Embolism (PE) is a condition that affects a multitude of individuals worldwide. The pathophysiology of PE is multifactorial and complex. Measuring levels of biomarkers in PE patient plasma may be predictive of patient outcomes in terms of survival, and such biomarkers could be correlated to other parameters such as white cell counts and their ratios. Adhesion molecules, such as selectins, have been predicted to play a role in the pathophysiology of PE, however their relationship to other cellular parameters is not fully explored. P-selectin is found on platelets, and is involved in the gathering of platelets in thrombotic states. Meanwhile, E and L-selectin contribute to cellular rolling that occurs in states of inflammation. White blood cell counts are routinely obtained from patient blood analysis. Selectins, including Platelet (P), Endothelial (E), and Leukocyte (L) Selectins may possess relationships to the white cell profiles including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), platelet-neutrophil ratio (PNR), lymphocyte-monocyte ratio (LMR), and monocyte-neutrophil ratio (MNR). Selectins can also be correlated to total platelet and white cell counts. Mortality outcomes in PE patients may be associated with altered levels of hemostatic and inflammatory biomarkers such as selectins. Materials and Methods: Blood samples were acquired from 100 patients diagnosed with acute PE between March 2016 and June 2019 at Loyola University Medical Center in Maywood, IL. Enzyme Linked Immunosorbent Assays (ELISA) were used to quantify levels of P, E, and L selectins in the plasma of PE patients. Other coagulation and inflammatory biomarkers, including Tumor Necrosis Factor Alpha (TNFa), D-dimer, Plasminogen Activating Inhibitor-1 (PAI-1), Matrix Metalloprotease-9 (MMP-9), C-Reactive Protein (CRP), micro particles, and alpha-2-antiplasmin were also quantified. Patient chart review was conducted assessing for levels of platelets, neutrophils, lymphocytes, and monocytes. Appropriate cellular ratios were calculated. Patient outcomes in the form of mortality were noted. Spearman non-parametric analysis and Wilcoxon-Mann-Whitney Tests were conducted using Graphpad PRISM software. Results: All of the biomarkers studied exhibited an increase in PE patient plasma, ranging from 2 fold to 34.6 fold increase, with the exception of alpha-2-antiplasmin, E-selectin, and L-selectin, as shown in Table 1. D-dimer, MMP-9, and CRP show the most pronounced increase in PE patients. No statistically significant correlations were noted between P, E, and L-selectins and NLR, PLR, PNR, LMR, or MNR. P-selectin was positively correlated with platelet count (r=.22, p=.032, 95% CI=0.01293 to 0.4084, n=95). L-selectin was not found to be significantly correlated with white count, but a positive trend was still evident (r=.13, p=.22, CI= -0.08329 to 0.3250, n=95). Within the patient pool, 12% of patients were deceased, while 88% survived. L-selectin and all-cause mortality were significantly correlated at an alpha level of .05 (p=.04). Conclusion: These studies demonstrate the marked dysregulation of hemostatic and inflammatory biomarkers associated with alterations of cellular indices. In particular, P and L selectin demonstrated some relationship to platelets and white count. L-selectin levels are significantly correlated to all-cause mortality. Measuring levels of L-selectin in PE patients may provide insight into mortality outcomes for pulmonary embolism patients. Our results are suggestive of the positive predictive value of L-selectin in PE patients. Profiling of various biomarkers, in particular selectins, may be helpful in the risk stratification of PE patients. Adding such a parameter to patient analysis may provide better prognostic information, which may be helpful in their clinical management. Disclosures No relevant conflicts of interest to declare.

scholarly journals Joint analysis of D-dimer, N-terminal pro b-type natriuretic peptide, and cardiac troponin I on predicting acute pulmonary embolism relapse and mortality

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoyu Liu ◽  
Liying Zheng ◽  
Jing Han ◽  
Lu Song ◽  
Hemei Geng ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Survival Rate ◽  
Adverse Events ◽  
Acute Pulmonary Embolism ◽  
Troponin I ◽  
All Cause Mortality ◽  
Long Term Prognosis ◽  
D Dimer

AbstractPrevious studies on the adverse events of acute pulmonary embolism (APE) were mostly limited to single marker, and short follow-up duration, from hospitalization to up to 30 days. We aimed to predict the long-term prognosis of patients with APE by joint assessment of D-dimer, N-Terminal Pro-Brain Natriuretic Peptide (NT-ProBNP), and troponin I (cTnI). Newly diagnosed patients of APE from January 2011 to December 2015 were recruited from three hospitals. Medical information of the patients was collected retrospectively by reviewing medical records. Adverse events (APE recurrence and all-cause mortality) of all enrolled patients were followed up via telephone. D-dimer > 0.50 mg/L, NT-ProBNP > 500 pg/mL, and cTnI > 0.40 ng/mL were defined as the abnormal. Kaplan–Meier curve was used to compare the cumulative survival rate between patients with different numbers of abnormal markers. Cox proportional hazard regression model was used to further test the association between numbers of abnormal markers and long-term prognosis of patients with APE after adjusting for potential confounding. During follow-up, APE recurrence and all-cause mortality happened in 78 (30.1%) patients. The proportion of APE recurrence and death in one abnormal marker, two abnormal markers, and three abnormal markers groups were 7.69%, 28.21%, and 64.10% respectively. Patients with three abnormal markers had the lowest survival rate than those with one or two abnormal markers (Log-rank test, P < 0.001). After adjustment, patients with two or three abnormal markers had a significantly higher risk of the total adverse event compared to those with one abnormal marker. The hazard ratios (95% confidence interval) were 6.27 (3.24, 12.12) and 10.7 (4.1, 28.0), respectively. Separate analyses for APE recurrence and all-cause death found similar results. A joint test of abnormal D-dimer, NT-ProBNP, and cTnI in APE patients could better predict the long-term risk of APE recurrence and all-cause mortality.

Prognostic Value of D-Dimer in Stable Patients with Pulmonary Embolism

2011 ◽  
Vol 17 (6) ◽  
pp. E183-E185 ◽  
Author(s):  
Paul D. Stein ◽  
Muhammad Janjua ◽  
Fadi Matta ◽  
Ahmed Alrifai ◽  
Fadel Jaweesh ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Hospital Mortality ◽  
High Mortality ◽  
Prognostic Value ◽  
Chart Review ◽  
Retrospective Chart Review ◽  
All Cause Mortality ◽  
D Dimer

Prognosis of pulmonary embolism (PE) based on levels ofD-dimer has shown mixed results, and data on in-hospital prognosis of stable patients are sparse. We assessed in-hospital prognosis in 292 stable patients with PE based on retrospective chart review using an arbitrarily selected value ofD-dimer ≥5000 ng/mL as cut-off level. In-hospital mortality from PE was 0% (0 of 222) withD-dimer <5000 ng/mL compared with 2.9% (2 of 70) withD-dimer ≥5000 ng/mL ( P = .06). In-hospital all-cause mortality was 2.3% (5 of 222) withD-dimer <5000 ng/mL compared with 2.9% (2 of 70) withD-dimer ≥5000 ng/mL (NS). Markedly elevated levels ofD-dimer, therefore, did not indicate a high mortality from PE or all-cause mortality during hospitalization.

scholarly journals Predictive Value of Cellular Blood Indices for All-Cause Mortality in Acute Pulmonary Embolism

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2103-2103
Author(s):  
Brett Slajus ◽  
Yevgeniy Brailovsky ◽  
Trung Phan ◽  
Iman Darwish ◽  
Jawed Fareed ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Predictive Value ◽  
Thrombotic Event ◽  
The United States ◽  
Predictive Values ◽  
Blood Indices ◽  
Lymphocyte Ratio ◽  
Chronic Inflammatory Condition ◽  
All Cause Mortality ◽  
Acute Pe

Introduction: Pulmonary embolism (PE) contributes to more than 100,000 annual deaths in the United States and is the third most common cause of cardiovascular death. Short-term all-cause mortality rates differ widely, from 2% among low risk normotensive patients to 95% among those experiencing cardiac arrest. Prognostic models for PE help clinicians facilitate decision making but have suboptimal predictive values. The most widely used tool is the simplified Pulmonary Embolism Severity Index (sPESI) - a scoring system which utilizes 6 clinical variables to predict death. Cellular indices, like platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR), have been shown to be markers of systemic inflammation and are associated with worsened prognosis in acute PE. Other ratios, such as lymphocyte-monocyte ratio (LMR) and platelet-neutrophil ratio (PNR), have not been fully explored. Given the need to further improve sPESI to better manage PE patients, we sought to determine the association of PLR, NLR, LMR, and PNR with all-cause mortality in patients presenting with acute PE. We also evaluated the additive effect of these cellular indices on the predictive value of sPESI. Methods: We retrospectively investigated patients who were consecutively diagnosed and treated between March 2016 and June 2019 at Loyola Medical Center in Maywood, Illinois and Gottlieb Memorial Hospital in Melrose Park, Illinois. Diagnosis of PE was made using CT pulmonary angiography or ventilation perfusion (VQ) scan. Patients were excluded if there was presence of infection, sepsis, ongoing cancer treatment, or a chronic inflammatory condition at the time of PE diagnosis. Clinical characteristics were collected using the electronic medical record system. Differential complete blood count data was collected within 24 hours prior to PE diagnosis. Mann Whitney U and Chi-Square tests were used to determine associations between all-cause mortality and clinical data. ROC curves were constructed to illustrate the sensitivity and specificity of cellular indices to predict all-cause mortality. Optimal ratio cutoffs were determined using Youden J Index. A composite sPESI score was created using cellular blood indices cutoff values. One point was added to the sPESI score for every additional condition met. Results: Among the 228 PE patients, 48 (21%) were non-survivors with median follow up period of 56 days (IQR: 17-182). Elevated PLR and NLR, as well as decreased LMR, were associated with all-cause mortality (all p < 0.01). PNR was not associated with all-cause mortality (p > 0.62). PLR > 256.7 was predictive of mortality (p < 0.01) with sensitivity 54.2% and specificity 85.6%. NLR > 5.5 was predictive of mortality (p < 0.01) with sensitivity 66.7% and specificity 68.3%. LMR < 1.6 was predictive of mortality (p < 0.01) with sensitivity 66.7% and specificity 70.8%. sPESI was predictive of mortality (p < 0.01) with sensitivity 72.9% and specificity 64.0%. A composite model including sPESI, PLR, NLR, and LMR had further improved predictive abilities for all-cause mortality with sensitivity 85.4% and specificity 66.3% as compared to sPESI alone (AUC: 0.82, 95% CI: 0.76-0.89 vs AUC 0.75, 95% CI: 0.68-0.83). Conclusion: This study demonstrated an association between PLR, NLR, and LMR and all-cause mortality in PE patients. Our findings were consistent with past literature and contribute to the argument that these routine laboratory tests can supplement existing risk prediction models. Lymphopenia as well as elevated neutrophil count are associated with pro-inflammatory states during cardiopulmonary events, which may increase risk for thrombotic events. Platelets, a key component of thrombosis, are significantly decreased immediately after a thrombotic event. The composite sPESI model, including PLR, NLR, and LMR exhibited higher sensitivity which allows for improved detection of patients who are at high risk for death. Future studies are required to assess the predictive value of other routine blood tests on all-cause mortality in this patient population to further optimize sPESI and other predictive tools. Disclosures No relevant conflicts of interest to declare.

scholarly journals Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios Predict All-Cause Mortality in Acute Pulmonary Embolism

2020 ◽  
Vol 26 ◽  
pp. 107602961990054 ◽  
Author(s):  
Trung Phan ◽  
Yevgeniy Brailovsky ◽  
Jawed Fareed ◽  
Debra Hoppensteadt ◽  
Omer Iqbal ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Acute Pulmonary Embolism ◽  
Prediction Models ◽  
Area Under The Curve ◽  
Neutrophil To Lymphocyte Ratio ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Useful Components ◽  
Significant Difference ◽  
All Cause Mortality

The aim of this study was to investigate the utility of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to predict all-cause mortality in patients presenting with acute pulmonary embolism (PE). Three hundred consecutive patients with acute PE between March 2016 and December 2018 were retrospectively analyzed. We identified 191 patients who met the study inclusion criteria. Twenty-eight patients died during the study period. There was a significant difference in PLR, but not NLR, between patients with low risk, submassive, and massive risk PE ( P = .02 and P = .58, respectively, by the Kruskal-Wallis test). Elevated NLR and PLR were associated with all-cause mortality ( P < .01 and P < .01, respectively). Neutrophil-to-lymphocyte ratio of 5.46 was associated with all-cause mortality with sensitivity of 75.0% and specificity of 66.9% (area under the curve [AUC]: 0.692 [95% confidence interval, CI]: 0.568-0.816); P < .01). Platelet-to-lymphocyte ratio of 256.6 was associated with all-cause mortality with sensitivity of 53.6% and specificity of 82.2% (AUC: 0.693 [95% CI: 0.580-0.805]; P < .01). Neutrophil-to-lymphocyte ratio and PLR are simple biomarkers that are readily available from routine laboratory values and may be useful components of PE risk prediction models.

scholarly journals Glomerular Filtration Rate as a Prognostic Factor for Long-Term Mortality after Acute Pulmonary Embolism

2019 ◽  
Vol 28 (3) ◽  
pp. 264-272 ◽  
Author(s):  
Valdis Ģībietis ◽  
Dana Kigitoviča ◽  
Barbara Vītola ◽  
Sintija Strautmane ◽  
Andris Skride
Keyword(s):  
Pulmonary Embolism ◽  
Glomerular Filtration Rate ◽  
Filtration Rate ◽  
Acute Pulmonary Embolism ◽  
All Cause Mortality ◽  
Acute Pe ◽  
D Dimer ◽  
Active Cancer ◽  
Long Term Mortality

Background: In-hospital mortality for patients presenting with acute pulmonary embolism (PE) has been reported to be up to 7 times higher for patients with decreased estimated glomerular filtration rate (eGFR). However, few studies have assessed its effect on long-term mortality. Objective: To determine the impact of eGFR and creatinine clearance (CrCl) on long-term all-cause mortality following acute PE in association with other routine laboratory analyses and comorbidities. Patients/Methods: The prospective study enrolled 141 consecutive patients presenting with objectively confirmed acute PE. Demographic, clinical data, comorbidities, and laboratory values were recorded. CrCl and GFR were estimated using the Cockcroft-Gault, MDRD, and chronic kidney disease (CKD)-EPI equations. Patients were followed up at 90 days and 1 year after the event. Results: In univariate analyses, age, active cancer, PE severity index (PESI), CrCl and eGFR, D-dimer value, and high-density lipoprotein level were found to be significantly associated with mortality in 90 days and 1 year. Additionally, body mass index was significant in the 1-year follow-up. CrCl by Cockcroft-Gault (90-day: area under the curve [AUC] 0.763; 1-year: AUC 0.718) demonstrated higher discriminatory power for predicting mortality than eGFR by the MDRD (AUC 0.686; AUC 0.609) and CKD-EPI (AUC 0.697; AUC 0.630) equations. In multivariate analyses, active cancer, CrCl by Cockcroft-Gault (90-day: hazard ratio [HR] 0.948, 95% CI 0.919–0.979; 1-year: HR 0.967, 95% CI 0.943–0.991), eGFR by CKD-EPI (90-day: HR 0.948, 95% CI 0.915–0.983; 1-year: HR 0.971, 95% CI 0.945–0.998) were found to be independent predictors of mortality. eGFR by MDRD, D-dimer, and PESI value were significant prognostic factors for 90-day mortality. Conclusion: Decreased renal function is a prognostic factor for increased all-cause mortality 90 days and 1 year after acute PE.

scholarly journals White cell counts in relation to mortality in a general population of cohort study in the Netherlands: a mediating effect or not?

BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e030949 ◽  
Author(s):  
Itziar Abete ◽  
Yunxia Lu ◽  
Camille Lassale ◽  
Monique Verschuren ◽  
Yvonne van der Schouw ◽  
...  
Keyword(s):  
Cox Regression ◽  
White Cell Count ◽  
Total Mortality ◽  
White Cell ◽  
Mediating Effect ◽  
Cell Counts ◽  
Risk Of Mortality ◽  
All Cause Mortality ◽  
Death Cases ◽  
Cvd Mortality

BackgroundWhite cell count (WCC) is a clinical marker of inflammation. Data are limited regarding the association of total and differential WCC with risk of mortality, and its role related with smoking and body mass index (BMI).MethodsA total of 14 433 participants (4150 men; 10 283 women; average age 47.3±11.8 years) from the Dutch European Prospective Investigation into Cancer and Nutrition-Netherlands cohort were included. The associations between prediagnostic total WCC and its subtypes and risk of all-cause, cancer and cardiovascular disease (CVD) mortality were assessed. The role of WCC related with smoking and BMI on mortality was further explored. Multivariate Cox regression models were performed to estimate the HR and 95% CI.ResultsAfter an average follow-up of 15.8 years, a total of 936 death cases were identified (466 cancer; 179 CVD; 291 other causes). Statistically significant graded associations between total WCC, and counts of lymphocytes, monocytes, neutrophils and eosinophils and risk of total mortality were observed. These associations were more apparent in current smokers. Strong associations for all-cause mortality or cancer mortality were observed in subjects with BMI ≥25 kg/m2, ever smoking and elevated WCC (HR 3.92, 95% CI 2.76 to 5.57; HR 3.93, 95% CI 2.30 to 6.72). WCC partly mediated the associations between smoking or BMI and all-cause mortality.ConclusionsPrediagnostic WCC and its subtypes are associated with all-cause, cancer and CVD mortality risk. It may play a partially mediate role on the association between smoking or obesity and mortality.

scholarly journals Ratios between circulating myeloid cells and lymphocytes are associated with mortality in severe COVID-19 patients

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 351-360
Author(s):  
Hui Ma ◽  
Xiong Chang Lim ◽  
Qihong Yu ◽  
Yi Li ◽  
Yuechuan Li ◽  
...  
Keyword(s):  
Myeloid Cells ◽  
Myeloid Cell ◽  
Laboratory Findings ◽  
Lymphocyte Ratio ◽  
Host Immune Responses ◽  
Cell Counts ◽  
Coagulation Status ◽  
Highly Correlated ◽  
The Impact ◽  
D Dimer

Abstract Recent studies indicate that host immune responses are dysregulated with either myeloid cell compartment or lymphocyte composition being disturbed in COVID-19. This study aimed to assess the impact of SARS-CoV-2 viral infection on the composition of circulating immune cells in severe COVID-19 patients. In this retrospective single-center cohort, 71 out of 87 COVID-19 patients admitted to the intense care unit for oxygen treatment were included in this study. Demographics, clinical features, comorbidities, and laboratory findings were collected on admission. Out of the 71 patients, 5 died from COVID-19. Compared with survived patients, deceased patients showed higher blood cell counts of neutrophils and monocytes but lower cell counts of lymphocytes. Intriguingly, the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and basophil-to-lymphocyte ratio (BLR) were markedly higher in deceased patients compared to survived patients. Furthermore, the lymphocyte counts were negatively correlated with D-dimer levels, while the ratios between myeloid cells and lymphocyte (NLR, MLR, and BLR) were positively correlated with D-dimer levels. Our findings revealed that the ratios between myeloid cells and lymphocytes were highly correlated with coagulation status and patient mortality in severe COVID-19.

Abstract 14049: Correlation of Cellular Indices and D-dimer/fibrinogen Ratio to Gender Differences in 6-minute Walk Test Distance in Patients Presenting With Acute Pulmonary Embolism

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nathalie Antonios ◽  
Dalila Masic ◽  
Katerina Porcaro ◽  
Sorcha Allen ◽  
Alexandru Marginean ◽  
...  
Keyword(s):  
Gender Differences ◽  
Pulmonary Embolism ◽  
Complete Blood Count ◽  
Walking Distance ◽  
Walk Test ◽  
Lymphocyte Ratio ◽  
Inflammatory State ◽  
Test Distance ◽  
Minute Walk ◽  
D Dimer

Introduction: The six-minute walk test (6MWT) is a simple and well-validated test to assess functional status and predict morbidity and mortality in several chronic cardiopulmonary disease states. Neutrophil to Lymphocyte ratio (NLR) reflects a pro inflammatory state. Increased platelet to lymphocyte ratio (PLR) has been associated with increase in thrombus burden. Elevated D-dimer to fibrinogen ratio (D/f) reflects fibrinolysis activation. No study has investigated the correlation of these indices with gender differences in 6MWT in patients presenting with pulmonary embolism (PE). Methods: We retrospectively evaluated all acute PE patients from our Pulmonary Embolism Response Team Registry who completed a 6MWT during their initial hospitalization. Differential complete blood count data along with d-dimer and fibrinogen were collected within 24 hours prior to PE diagnosis. Results: A total of 186 patients underwent baseline 6MWT and lab tests between March 2016 and January 2020. The mean walking distance for males (765 ft) was further than females (519 ft; figure 1). NLR, PLR, and D/f did not correlate with 6MWT in males. In females, NLR, PLR, and D/f had a negative correlation with walking distance (r = -0.20, p <0.05; r = -3.0, p<0.01; and r = -0.15, p<0.05; figure 2) Conclusions: Female patients, in our study, had significantly shorter walking distance after acute presentation in PE. This may reflect higher inflammatory and prothrombotic state. Future studies will need to expand on these findings.

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