Associations of longitudinal D-Dimer and Factor II on early trauma survival risk

Abstract Background Trauma-induced coagulopathy (TIC) is a disorder that occurs in one-third of severely injured trauma patients, manifesting as increased bleeding and a 4X risk of mortality. Understanding the mechanisms driving TIC, clinical risk factors are essential to mitigating this coagulopathic bleeding and is therefore essential for saving lives. In this retrospective, single hospital study of 891 trauma patients, we investigate and quantify how two prominently described phenotypes of TIC, consumptive coagulopathy and hyperfibrinolysis, affect survival odds in the first 25 h, when deaths from TIC are most prevalent. Methods We employ a joint survival model to estimate the longitudinal trajectories of the protein Factor II (% activity) and the log of the protein fragment D-Dimer ($$\upmu$$ μ g/ml), representative biomarkers of consumptive coagulopathy and hyperfibrinolysis respectively, and tie them together with patient outcomes. Joint models have recently gained popularity in medical studies due to the necessity to simultaneously track continuously measured biomarkers as a disease evolves, as well as to associate them with patient outcomes. In this work, we estimate and analyze our joint model using Bayesian methods to obtain uncertainties and distributions over associations and trajectories. Results We find that a unit increase in log D-Dimer increases the risk of mortality by 2.22 [1.57, 3.28] fold while a unit increase in Factor II only marginally decreases the risk of mortality by 0.94 [0.91,0.96] fold. This suggests that, while managing consumptive coagulopathy and hyperfibrinolysis both seem to affect survival odds, the effect of hyperfibrinolysis is much greater and more sensitive. Furthermore, we find that the longitudinal trajectories, controlling for many fixed covariates, trend differently for different patients. Thus, a more personalized approach is necessary when considering treatment and risk prediction under these phenotypes. Conclusion This study reinforces the finding that hyperfibrinolysis is linked with poor patient outcomes regardless of factor consumption levels. Furthermore, it quantifies the degree to which measured D-Dimer levels correlate with increased risk. The single hospital, retrospective nature can be understood to specify the results to this particular hospital’s patients and protocol in treating trauma patients. Expanding to a multi-hospital setting would result in better estimates about the underlying nature of consumptive coagulopathy and hyperfibrinolysis with survival, regardless of protocol. Individual trajectories obtained with these estimates can be used to provide personalized dynamic risk prediction when making decisions regarding management of blood factors.

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Glycated Hemoglobin as a Marker for Predicting Outcomes of Patients With Stroke (Ischemic and Hemorrhagic): A Systematic Review and Meta-Analysis

Frontiers in Neurology ◽

10.3389/fneur.2021.642899 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yaya Bao ◽

Dadong Gu

Keyword(s):

Functional Outcome ◽

Hemorrhagic Stroke ◽

Glycated Hemoglobin ◽

Meta Analysis ◽

Poor Functional Outcome ◽

Risk Of Mortality ◽

Increased Risk ◽

Unit Increase ◽

Symptomatic Intracranial Hemorrhage ◽

The Relationship

Background: Glycated hemoglobin (HbA1c) has emerged as a useful biochemical marker reflecting the average glycemic control over the last 3 months, and the values are not affected by short-term transient changes in blood glucose levels. However, its prognostic value in the acute neurological conditions such as stroke is still not well-established. The present meta-analysis was conducted to assess the relationship of HbA1c with outcomes such as mortality, early neurological complications, and functional dependence in stroke patients.Methods: A systematic search was conducted for the PubMed, Scopus, and Google Scholar databases. Studies, either retrospective or prospective in design that examined the relationship between HbA1c with outcomes of interest and presented the strength of association in the form of adjusted odds ratio/hazard ratios were included in the review. Statistical analysis was done using STATA version 13.0.Results: A total of 22 studies (15 studies on acute ischemic stroke and seven studies on hemorrhagic stroke) were included in the meta-analysis. For patients with acute ischemic stroke, each unit increase in HbA1c was found to be associated with an increased risk of mortality within 1 year, increased risk of poor functional outcome at 3 months, and an increased risk of symptomatic intracranial hemorrhage (sICH) within 24 h of admission. In those with HbA1c ≥ 6.5%, there was an increased risk of mortality within 1 year of admission, increased risk of poor functional outcomes at 3 and 12 months as well as an increased risk of symptomatic intracranial hemorrhage (sICH) within 24 h of admission. In patients with hemorrhagic stroke, each unit increase in HbA1c was found to be associated with increased risk of poor functional outcome within the first 3 months from the time of admission for stroke. In those with HbA1c ≥ 6.5%, there was an increased risk of poor functional outcome at 12 months.Conclusions: The findings indicate that glycated hemoglobin (HbA1c) could serve as a useful marker to predict the outcomes in patients with stroke and aid in the implementation of adequate preventive management strategies at the earliest.

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Temporal Changes in Fibrinolysis following Injury

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0039-1701016 ◽

2020 ◽

Vol 46 (02) ◽

pp. 189-198 ◽

Cited By ~ 2

Author(s):

Hunter B. Moore ◽

Ernest E. Moore

Keyword(s):

Fibrinolytic Activity ◽

Tissue Injury ◽

Plasminogen Activator Inhibitor ◽

Trauma Patients ◽

Plasminogen Activator Inhibitor 1 ◽

Therapeutic Implications ◽

Risk Of Mortality ◽

Increased Risk ◽

The Individual ◽

Global Transition

AbstractTrauma patients present to the emergency department with a spectrum of fibrinolytic activity. This wide variance in fibrinolysis activity is a complex multifactorial process impacted by the degree of hemorrhagic shock and the amount of tissue injury the individual sustains. The fibrinolytic activity of the trauma patient at presentation to the hospital has prognostic and therapeutic implications. Those patients with high fibrinolytic activity (hyperfibrinolysis) are at risk of mortality from hemorrhage, whereas those patients with low fibrinolytic activity (shutdown or hypofibrinolysis) are at an increased risk of delayed mortality from traumatic brain injury or organ failure. These phenotypes of fibrinolysis acutely following injury change with resuscitation, and the majority of trauma patients will transition to a fibrinolytic resistant state several hours after injury. The mechanism for this near-global transition to this acquired fibrinolysis appears to be related to the generation of plasminogen activator inhibitor-1 in the liver. Those patients who do not recover from this fibrinolytic state 24 hours after injury have a poor prognosis. The purpose of this article is to review the different states of fibrinolytic activity following injury and how they change over time following resuscitation and in the intensive care unit.

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D-dimer levels on admission and all-cause mortality risk in COVID-19 patients: a meta-analysis

Epidemiology and Infection ◽

10.1017/s0950268820002022 ◽

2020 ◽

Vol 148 ◽

Author(s):

Daniel Martin Simadibrata ◽

Anna Mira Lubis

Keyword(s):

Sensitivity Analysis ◽

Mortality Risk ◽

Meta Analysis ◽

Prognostic Role ◽

Chinese Studies ◽

Risk Of Mortality ◽

Increased Risk ◽

All Cause Mortality ◽

D Dimer ◽

Overall Mortality

Abstract D-dimer level on admission is a promising biomarker to predict mortality in patients with COVID-19. In this study, we reviewed the association between on-admission D-dimer levels and all-cause mortality risk in COVID-19 patients. Peer-reviewed studies and preprints reporting categorised D-dimer levels on admission and all-cause mortality until 24 May 2020 were searched for using the following keywords: ‘COVID-19’, ‘D-dimer’ and ‘Mortality’. A meta-analysis was performed to determine the pooled risk ratio (RR) for all-cause mortality. In total, 2911 COVID-19 patients from nine studies were included in this meta-analysis. Regardless of the different D-dimer cut-off values used, the pooled RR for all-cause mortality in patients with elevated vs. normal on-admission D-dimer level was 4.77 (95% confidence interval (CI) 3.02–7.54). Sensitivity analysis did not significantly affect the overall mortality risk. Analysis restricted to studies with 0.5 μg/ml as the cut-off value resulted in a pooled RR for mortality of 4.60 (95% CI 2.72–7.79). Subgroup analysis showed that the pooled all-cause mortality risk was higher in Chinese vs. non-Chinese studies (RR 5.87; 95% CI 2.67–12.89 and RR 3.35; 95% CI 1.66–6.73; P = 0.29). On-admission D-dimer levels showed a promising prognostic role in predicting all-cause mortality in COVID-19 patients, elevated D-dimer levels were associated with increased risk of mortality.

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Elevated D-Dimer Levels are Associated with Increased Risk of Mortality in COVID-19: A Systematic Review and Meta-Analysis

10.1101/2020.04.29.20085407 ◽

2020 ◽

Cited By ~ 3

Author(s):

Siddharth Shah ◽

Kuldeep Shah ◽

Siddharth B Patel ◽

Forum S Patel ◽

Mohammed Osman ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Severe Disease ◽

Case Fatality ◽

Inclusion Criteria ◽

Risk Of Mortality ◽

Increased Risk ◽

Novel Coronavirus ◽

D Dimer

AbstractIntroductionThe 2019 novel Coronavirus (2019-nCoV), now declared a pandemic has an overall case fatality of 2–3% but it is as high as 50% in critically ill patients. D-dimer is an important prognostic tool, often elevated in patients with severe COVID-19 infection and in those who suffered death. In this systematic review, we aimed to investigate the prognostic role of D-dimer in COVID-19 infected patients.MethodsWe searched PubMed, Medline, Embase, Ovid, and Cochrane for studies reporting admission D-dimer levels in COVID-19 patients and its effect on mortality.Results18 studies (16 retrospective and 2 prospective) with a total of 3,682 patients met the inclusion criteria. The pooled mean difference (MD) suggested significantly elevated D-dimer levels in patients who died versus those survived (MD 6.13 mg/L, 95% CI 4.16 − 8.11, p <0.001). Similarly, the pooled mean D-dimer levels were significantly elevated in patients with severe COVID-19 infection (MD 0.54 mg/L, 95% CI 0.28 − 0.8, p< 0.001). In addition, the risk of mortality was four-fold higher in patients with positive D-dimer vs negative D-dimer (RR 4.11, 95% CI 2.48 − 6.84, p< 0.001) and the risk of developing the severe disease was two-fold higher in patients with positive D-dimer levels vs negative D-dimer (RR 2.04, 95% CI 1.34 − 3.11, p < 0.001).ConclusionOur meta-analysis demonstrates that patients with COVID-19 presenting with elevated D-dimer levels have an increased risk of severe disease and mortality.

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The Role of Neutrophil Extracellular Traps in Cancer-Associated Arterial Thrombosis

Blood ◽

10.1182/blood-2018-99-116104 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2508-2508

Author(s):

Ella Grilz ◽

Lisa-Marie Mauracher ◽

Oliver Königsbrügge ◽

Florian Posch ◽

Irene Lang ◽

...

Keyword(s):

Overall Survival ◽

Neutrophil Extracellular Traps ◽

Categorical Variables ◽

Study Cohort ◽

Patients With Cancer ◽

Extracellular Traps ◽

Kaplan Meier ◽

Risk Of Mortality ◽

Increased Risk ◽

Unit Increase

Abstract Introduction: Prior studies have indicated that Neutrophil extracellular traps (NETs) trigger arterial thromboembolism (ATE) and play a role in the pathogenesis of cancer-associated venous thrombosis. We investigated the association between NET biomarkers (citrullinated histone H3 [H3Cit], cell-free DNA [cfDNA], and nucleosomes) and the risk of ATE in patients with cancer. Methods: In this prospective cohort study, H3Cit, cfDNA and nucleosome levels were determined at study inclusion, and patients with newly diagnosed cancer or progressive disease after remission were followed for 2 years for objectively confirmed, symptomatic ATE and death. Fine&Gray competing-risk regression was used to model risk of ATE. Overall survival (OS) was analyzed with Kaplan-Meier estimators. Results: Nine-hundred and fifty-eight patients with cancer (median age: 61 years; 46.8% female; Table 1) were recruited. ATE occurred in 22 patients; the cumulative 6-, 12-, and 24-month risks of ATE were 1.1%, 1.8%, and 2.3%, respectively. The subdistribution hazard ratios (SHR) for ATE of H3Cit, cfDNA, and nucleosomes per unit increase were 1.0 (95% confidence interval [CI]: 1.0-1.0, p=.882), 1.0 (1.0-1.0, p=.639), and 1.1 (1.0-1.2, p=.246) respectively. The 6-, 12-, and 24-month ATE probability was 1.3%, 1.7%, and 2.6% in patients with a H3Cit level ≤ 75thpercentile, and 0.8%, 1.3%, and 1.7% in patients above this cut-off (SHR=0.7, 0.2-2.0, p=.460). The 6-, 12-, 24-month overall survival of the study cohort was 87.0% (95%CI: 84.6-89.0), 73.6% (70.6-76.3), and 57.6% (54.3-60.8), respectively. The hazard ratio (HR) for mortality of H3Cit, cfDNA, and nucleosomes per unit increase were 1.0 (1.0-1.0, p<.001), 1.0 (1.0-1.0, p<.001), and 1.0 (1.0-1.1, p=.181) respectively. For better illustration we defined two groups of patients with elevated or non-elevated NET biomarkers. Therefore, we set an empiric cut-off at the 75thpercentile of the study cohort. Elevated H3Cit (HR=1.7, 1.3-2.1, p<.001), and cfDNA levels (HR=1.4, 1.1-1.7, p=.008) were associated with an increased risk of mortality after adjusting for age, and sex (Figure 1A&B). No association was found between higher nucleosome levels and the risk of all-cause mortality in patients with cancer (HR=1.2, 1.0-1.5, p=.088, Figure 1C). Conclusion: There was no significant association between H3Cit, cfDNA, and nucleosomes and ATE occurrence in patients with cancer. However, elevated levels of H3Cit, and cfDNA, were independently associated with an increased risk of mortality in patients with cancer. Table 1. Baseline characteristics of the total study population. Continuous data is reported as medians with first and third quartiles. Categorical variables are given as absolute frequencies and percentages. Data on body mass index, and cancer stage are missing in 2, and 76 patients, respectively. aPatients with brain and hematologic cancer Figure 1. Kaplan-Meier estimated for overall survival probability of patients with cancer according to baseline H3Cit, cfDNA, and nucleosome levels. MoM = Multiple-of-the-mean (i.e. Nucleosome results were compared to pooled plasma from 5 young male healthy controls to obtain a multiple-of-the-median) Disclosures No relevant conflicts of interest to declare.

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Incidence, morbidity, and mortality of traumatic superior mesenteric artery injuries compared to other visceral arteries

Vascular ◽

10.1177/1708538119893827 ◽

2019 ◽

Vol 28 (2) ◽

pp. 142-151

Author(s):

Shelley Maithel ◽

Areg Grigorian ◽

Roy M Fujitani ◽

Nii-Kabu Kabutey ◽

Brian M Sheehan ◽

...

Keyword(s):

Superior Mesenteric Artery ◽

Mesenteric Artery ◽

Inferior Mesenteric Artery ◽

Celiac Artery ◽

Visceral Artery ◽

Trauma Patients ◽

Mechanism Of Injury ◽

Artery Injury ◽

Risk Of Mortality ◽

Increased Risk

Objectives Celiac artery, superior mesenteric artery, and inferior mesenteric artery injuries are often grouped together as major visceral artery injuries with an incidence of <1%. The mortality rates range from 38–75% for celiac artery injuries and 25–68% for superior mesenteric artery injuries. No large series have investigated the mortality rate of inferior mesenteric artery injuries. We hypothesize that from all the major visceral artery injuries, superior mesenteric artery injury leads to the highest risk of mortality in adult trauma patients. Methods The Trauma Quality Improvement Program (2010–2016) was queried for patients with injury to the celiac artery, superior mesenteric artery, or inferior mesenteric artery. A multivariable logistic regression model was used for analysis. Separate subset analyses using blunt trauma patients and penetrating trauma patients were performed. Results From 1,403,466 patients, 1730 had single visceral artery injuries with 699 (40.4%) involving the celiac artery, 889 (51.4%) involving the superior mesenteric artery, and 142 (8.2%) involving the inferior mesenteric artery. The majority of patients were male (79.2%) with a median age of 39 years old, and median injury severity score of 22. Compared to celiac artery and inferior mesenteric artery injuries, superior mesenteric artery injuries had a higher rate of severe (grade >3) abbreviated injury scale for the abdomen (57.5% vs. 42.5%, p < 0.001). The overall mortality for patients with a single visceral artery injury was 20%. Patients with superior mesenteric artery injury had higher mortality compared to those with celiac artery and inferior mesenteric artery injuries (23.7% vs. 16.3%, p < 0.001). After controlling for covariates, traumatic superior mesenteric artery injury increased risk of mortality (OR = 1.72, CI = 1.24–2.37, p < 0.01) in adult trauma patients, while celiac artery ( p = 0.59) and inferior mesenteric artery ( p = 0.31) injury did not. After stratifying by mechanism, superior mesenteric artery injury increased risk of mortality (OR = 3.65, CI = 2.01–6.45, p < 0.001) in adult trauma patients with penetrating mechanism of injury but not in those with blunt force mechanism (OR = 1.22, CI = 0.81–1.85, p = 0.34). Conclusions Compared to injuries of the celiac artery and inferior mesenteric artery, traumatic superior mesenteric artery injury is associated with a higher mortality. Moreover, while superior mesenteric artery injury does not act as an independent risk factor for mortality in adult patients with blunt force trauma, it nearly quadruples the risk of mortality in adult trauma patients with penetrating mechanism of injury. Future prospective research is needed to confirm these findings and evaluate factors to improve survival following major visceral artery injury.

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Predictors of mortality for patients with COVID-19 and large vessel occlusion

Interventional Neuroradiology ◽

10.1177/1591019920954603 ◽

2020 ◽

Vol 26 (5) ◽

pp. 623-628 ◽

Cited By ~ 3

Author(s):

David J Altschul ◽

Charles Esenwa ◽

Neil Haranhalli ◽

Santiago R Unda ◽

Rafael de La Garza Ramos ◽

...

Keyword(s):

Cigarette Smoking ◽

Large Vessel ◽

Large Vessel Occlusion ◽

Vessel Occlusion ◽

Old Patients ◽

Risk Of Mortality ◽

Increased Risk ◽

History Of ◽

Radiographic Data ◽

D Dimer

Background This study evaluates the mortality risk of patients with emergent large vessel occlusion (ELVO) and COVID-19 during the pandemic. Methods We performed a retrospective cohort study of two cohorts of consecutive patients with ELVO admitted to a quaternary hospital from March 1 to April 17, 2020. We abstracted data from electronic health records on baseline, biomarker profiles, key time points, quality measures and radiographic data. Results Of 179 patients admitted with ischemic stroke, 36 had ELVO. Patients with COVID-19 and ELVO had a higher risk of mortality during the pandemic versus patients without COVID-19 (OR 16.63, p = 0.004). An age-based sub-analysis showed in-hospital mortality in 60% of COVID-19 positive patients between 61-70 years-old, 66.7% in between 51-60 years-old, 50% in between 41-50 years-old and 33.3% in between 31-40 years old. Patients that presented with pulmonary symptoms at time of stroke presentation had 71.4% mortality rate. 27.3% of COVID-19 patients presenting with ELVO had a good outcome at discharge (mRS 0-2). Patients with a history of cigarette smoking (p = 0.003), elevated d-dimer (p = 0.007), failure to recanalize (p = 0.007), and elevated ferritin levels (p = 0.006) had an increased risk of mortality. Conclusion Patients with COVID-19 and ELVO had a significantly higher risk for mortality compared to COVID-19 negative patients with ELVO. A small percentage of COVID-19 ELVO patients had good outcomes. Age greater than 60 and pulmonary symptoms at presentation have higher risk for mortality. Other risk factors for mortality were a history of cigarette smoking, elevated, failure to recanalize, elevated d-dimer and ferritin levels.

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Elevated D-dimer levels on admission are associated with severity and increased risk of mortality in COVID-19: A systematic review and meta-analysis

The American Journal of Emergency Medicine ◽

10.1016/j.ajem.2020.09.018 ◽

2021 ◽

Vol 39 ◽

pp. 173-179 ◽

Cited By ~ 1

Author(s):

Baris Gungor ◽

Adem Atici ◽

Omer Faruk Baycan ◽

Gokhan Alici ◽

Fatih Ozturk ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Risk Of Mortality ◽

Increased Risk ◽

D Dimer

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Elevated d-Dimer Levels Are Associated With Increased Risk of Mortality in Coronavirus Disease 2019

Cardiology in Review ◽

10.1097/crd.0000000000000330 ◽

2020 ◽

Vol 28 (6) ◽

pp. 295-302 ◽

Cited By ~ 5

Author(s):

Siddharth Shah ◽

Kuldeep Shah ◽

Siddharth B. Patel ◽

Foram S. Patel ◽

Mohammed Osman ◽

...

Keyword(s):

Risk Of Mortality ◽

Increased Risk ◽

D Dimer

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P1478LOWERING PREVALENCE OF ALKALOSIS AND IMPROVING ADHERENCE TO BICARBONATE TARGETS AMONGST HAEMODIALYSIS PATIENTS THROUGH THE USE OF REDUCED DIALYSATE BICARBONATE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1478 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Caroline Tulley ◽

Richard Hull ◽

Martin Ford

Keyword(s):

Patient Outcomes ◽

Patient Survival ◽

Target Range ◽

Serum Bicarbonate ◽

Bicarbonate Concentration ◽

Ongoing Debate ◽

Risk Of Mortality ◽

Increased Risk ◽

The Mean ◽

Small Change

Abstract Background and Aims There is evidence that metabolic alkalosis in haemodialysis patients is harmful. Bommer et al demonstrated association between extremes of bicarbonate and clinical outcomes with significantly increased risk of mortality and hospitalisation with pre-dialysis serum bicarbonate >27mmol/L and <17mmol/L. No overall increased mortality risk was observed with moderate pre-dialysis acidosis (serum bicarbonate 19.1-23.0mmol/L). 2015 Renal Registry Data demonstrated 64.3% of haemodialysis patients overall had bicarbonates within target (18-24mmol/L) compared to 65.7% within our centre. Our reported mean pre-dialysis bicarbonate of 23.7mmol/L was above the mean serum bicarbonate 23.2mmol/L seen nationally. In addition, 33.7% of patients were alkalotic, with bicarbonates >24mmol/L. Given concerns of adverse patient outcomes with extremes of bicarbonate, we aimed to investigate whether reducing our dialysate bicarbonate would culminate in overall attainment of bicarbonate targets. Method Mid-week pre-dialysis bicarbonate levels were measured from in centre haemodialysis patients once monthly, from May to August 2017, across 7 dialysis units within our renal service. Following this, in early 2018, we reduced dialysate bicarbonate concentration from 32mmol/L to 31mmol/L. Monthly midweek pre-dialysis bicarbonate levels were then re-measured in March and April 2019. Results Initial analysis of 2103 pre-dialysis bicarbonate levels across May to August 2017 demonstrated median monthly bicarbonate levels of 24.0–25.0mmol/L. 40.7–54.2% (n=199-322) were alkalotic with pre-dialysis bicarbonates >24mmol/L across this period. Of note, 15-23% (n=66-120) had bicarbonate levels associated with increased mortality and hospitalisation (i.e. <17mmol/L or >27 mmol/L. Subsequent analysis of 1070 bicarbonate levels in March and April 2019 demonstrated a reduction in median pre-dialysis bicarbonate to 22.0mmol/L. Similarly, the proportion of alkalotic patients fell to 11.9–15.3% (n=71-91). 5-9% (n=26-46) bicarbonates were <17 or >27mmol/L. In March 2019, 77.9% of patients had serum bicarbonates in target range compared to 65.7% reported in 2015 overall. Conclusion Initial findings demonstrated substantial alkalosis amongst our dialysis population. A simple measure of altering dialysate by 1mmol/L achieved reductions in overall alkalaemia, and in turn, reduced the percentage of patients with bicarbonate values theoretically correlating with increased mortality and hospitalization risk. We have demonstrated that a small change in dialysate bicarbonate increased concordance with bicarbonate targets, without subsequent increased acidaemia. The extent to which adherence with such targets impacts on patient survival and morbidity remains an ongoing debate.

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