Association Of D-dimer Research Articles

Elevated markers of early fibrinolysis disorder as predictors of poor 90-day prognosis in patients with aneurysmal subarachnoid hemorrhage: A large prospective cohort study

ObjectivesEarly fibrinolysis disorder exists in aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate the association of markers of early fibrinolysis disorder with poor 90-day prognosis in patients with aSAH. Materials and MethodsA total of 693 consecutive aSAH patients from April 2020 to December 2022 were selected from the Long-term Prognosis of Emergency Aneurysmal Subarachnoid Hemorrhage (LongTEAM) trial. Poor 90-day prognosis was defined as a modified Rankin Scale 3-6 at 90 days after discharge. D-dimer (DD) and Fibrin degradation product (FDP) levels on admission were used to assess fibrinolysis disorder and patients were classified according to their quartiles. Multivariable logistic regression analysis was used to determine the association. ResultsOf 693 patients included, 131 (18.9%) had poor 90-day prognosis. Patients in the highest quartile of DD and FDP levels had higher risk of poor 90-day prognosis than those in the first quartile (DD: adjusted odds ratio [aOR]=2.22, 95% confidence interval [CI], 1.13-4.36, p = 0.021; FDP: aOR=2.87, 95% CI, 1.48-5.58, p = 0.002), after adjusting for potential risk factors. Meanwhile, a linear dose-response relationship between DD and FDP and poor 90-day prognosis was found. Subgroup analysis showed that DD and FDP were consistently associated with poor 90-day prognosis across subgroups, and no intergroup interaction was found. Interestingly, the associations of DD and FDP with poor 90-day prognosis were more significant in low-grade aSAH patients. ConclusionsElevated markers of early fibrinolysis disorder, including DD and FDP on admission, were associated with poor 90-day prognosis in aSAH patients.

Association of D-Dimer, C-Reactive Protein, and Ferritin with COVID-19 Severity in Pregnant Women: Important Findings of a Cross-Sectional Study in Northern Brazil.

The COVID-19 pandemic has had a great impact on pregnant women due to the broad clinical spectrum of the disease. The present study investigated the profile of three biomarkers during hospital admission of pregnant women-D-dimer, C-reactive protein (CRP), and ferritin-and their correlation with the severity and outcome of COVID-19. The cross-sectional study included 226 pregnant women hospitalized in the city of Belém, Pará, Northern Brazil, from April 2020 to July 2021. Epidemiological and laboratory data were obtained from medical records, and all pregnant women underwent RT-PCR molecular testing for the detection of SARS-CoV-2. In total, 121 (53.5%) were positive and 105 (46.5%) were negative for SARS-CoV-2 using RT-PCR. Most pregnant women (49.5%) with COVID-19 were between 26 and 34 years old, were residing in the interior of the state of Pará (51.2%), and were in the third gestational trimester (71.9%). In addition, 71.1% of them were admitted to the ward and 28.9% were admitted to the intensive care unit (ICU), with 90.9% surviving COVID-19. The concentrations of D-dimer (p = 0.0122) and ferritin (p ≤ 0.0001) were significantly higher among pregnant women with COVID-19, especially among those hospitalized in the ICU. Ferritin and D-dimer seem to serve as important biomarkers for the prognosis of COVID-19 in pregnant women, which was not observed for CRP.

D-dimer and the risk of hypertension: The REasons for Geographic And Racial Differences in Stroke Cohort Study

BackgroundReasons for increased risk of hypertension in Black compared with White people are only partly understood. D-dimer, a thrombo-inflammatory marker higher in Black individuals, is also higher in people with hypertension. However, the impact of D-dimer on racial disparities in risk of incident hypertension has not been studied. ObjectivesTo assess whether D-dimer is associated with the risk of incident hypertension, whether the association between D-dimer and the risk of incident hypertension differs by race, and whether the biology reflected by D-dimer explains racial disparities in the risk of incident hypertension. MethodsThis study included 1867 participants in the REasons for Geographic And Racial Differences in Stroke cohort study without baseline hypertension and with a second visit 9.4 years after baseline. Risk ratios of incident hypertension by baseline D-dimer level were estimated, a D-dimer–by–race interaction was tested, and the mediating effect of D-dimer (which represents underlying biological processes) on the association of race and hypertension risk was assessed. ResultsThe risk of incident hypertension was 47% higher in persons in the top quartile than in those in the bottom quartile of D-dimer (risk ratio [RR]: 1.47; 95% CI: 1.23-1.76). The association was partly attenuated after adjusting for sociodemographic and adiposity-related risk factors (RR: 1.22; 95% CI: 1.02-1.47). The association of D-dimer and hypertension did not differ by race, and D-dimer did not attenuate the racial difference in the risk of incident hypertension. ConclusionD-dimer concentration reflects pathophysiology related to the development of hypertension. Specific mechanisms require further study and may involve adiposity.

Association of D-dimer with estimated glomerular filtration rate in chronic kidney disease at different stages in Indian population

: Hyper-coagulability followed by cardiovascular disease is the most common cause of mortality in CKD (chronic kidney disease). Diagnostic usefulness of hypercoagulability marker at various stages of CKD needs to be assessed. : An observational cross-sectional study.: Dept of Biochemistry, Institute of Nephrourology, Bangalore, India from January 2022 to March 2022.Study population consists of CKD patients attending Nephrology outpatient for follow up. They were categorized into 5 stages using eGFR values. Laboratory test including D-Dimer was assayed in all the participants using Abbott Architect ci4100 analyzer. In our study, a peaked and statistically significant (P value = <0.0001) D-Dimer values were observed in stage 4&5 (5.4 ±2.5) in comparison with stage 1, 2 & 3 (0.9±0.2). D- Dimer had strong negative correlationR= - 0.79 with eGFR in stage 5 CKD. D-Dimer assay should be considered as a part of routine investigations in CKD patients especially in developing countries like India, where most of the patients reach hospital only at the later stages of the disease, in order to achieve a better follow-up and management of the disease.

Clinical Significance of Plasma D-Dimer and Fibrinogen in Outcomes after Stroke: A Systematic Review and Meta-Analysis

Background: There is increasing evidence on the prognostic significance of D-dimer and fibrinolysis in stroke. However, the systematic analysis of their relationship with adverse outcomes after stroke is lacking. Herein, we comprehensively assessed the correlation of D-dimer and fibrinolysis with stroke outcomes through meta-analysis. Methods: Studies for systematic literature review were retrieved from PubMed, EMBASE, and Cochrane Library databases. The association of D-dimer and fibrinolysis with outcomes of stroke patients was expressed as an odds ratio (OR) with 95% confidence intervals (95% CI). Results: Totally, 52 studies comprising 21,473 stroke patients were included. The results showed that the high D-dimer level was significantly associated with peripheral venous thrombosis after stroke (OR 1.03, 95% CI 1.01–1.05), poor outcome (MRS >2) after stroke (OR 1.731, 95% CI 1.464–2.048), death after stroke (OR 2.367, 95% CI 1.737–3.224), stroke recurrence (OR 1.229, 95% CI 1.113–1.358), and early neurologic deterioration (NIHSS >4) (OR 1.791, 95% CI 1.117–2.870). Moreover, high fibrinogen level was significantly associated with poor outcome (MRS >2) after stroke (OR 1.650, 95% CI 1.314–2.071), death after stroke (OR 1.310, 95% CI 1.128–1.520), stroke recurrence (OR 1.228, 95% CI 1.166–1.422), early neurologic deterioration (NIHSS >4) (OR 2.381, 95% CI 1.156–4.904), and coronary events after stroke (OR 1.427, 95% CI 1.232–1.653). Conclusion: Fibrinogen and D-dimer may be associated with adverse outcomes in patients with stroke, suggesting that they may serve as possible biomarkers for post-stroke adverse outcomes.

Association of D-dimer with short-term risk of venous thromboembolism in acutely ill medical patients: A systematic review and meta-analysis.

D-dimer, a marker of ongoing procoagulant activity, has been widely used for the diagnosis of venous thromboembolism (VTE). The prognostic significance of D-dimer in stratifying VTE risk for acutely ill medical patients has not been well-established. A literature search was performed to collect studies that compared the incidence of short-term VTE between acutely ill medical patients with elevated or nonelevated D-dimer levels. The cutoff of D-dimer was 0.5 μg/mL or otherwise defined by included studies. The study endpoint was any occurrence of VTE (inclusive of deep vein thrombosis [DVT], pulmonary embolism, or VTE-related death) within 90 days of hospital presentation. A meta-analytic approach was employed to estimate the odds ratio (OR) with 95% CI by fitting random-effects models using the generic inverse variance weighted approach. A total of 10 studies representing 31,119 acutely ill medical patients were included. Compared to those with nonelevated D-dimer levels, patients with elevated D-dimer had approximately threefold greater odds for short-term VTE within 90 days (OR, 3.28; 95% CI, 2.44 to 4.40; p < 0.0001). The association of elevated D-dimer with VTE composite (OR, 3.33; 95% CI, 2.20 to 5.02) and with DVT (OR, 3.26; 95% CI, 2.32 to 4.58) was comparable. The association was significant among patients who presented various acute medical illness (OR, 2.68; 95% CI, 2.01 to 3.58) and those who presented with acute stroke (OR, 3.25; 95% CI, 2.31 to 4.58). Elevation of D-dimer was predictive of the occurrence of VTE within 90 days among acutely ill medical patients.

Association of D-dimer with long-term prognosis in type 2 diabetes mellitus patients with acute coronary syndrome

Background and aimsType 2 diabetes mellitus (DM) accounts for more and more individuals worldwide. D-dimer has been demonstrated to be associated with cardiovascular diseases. The aim is to study the potential impact of D-dimer on the long-term prognosis of acute coronary syndrome (ACS) in the special population with type 2 DM. Methods and resultsA total of 2265 consecutive patients with DM and ACS were eligible in the study. Patients were divided into four groups according to quartiles of D-dimer concentration. Univariate and multivariate Cox regression analysis were conducted to explore the prognostic value of D-dimer for future outcomes. Patients with higher level of D-dimer presented with higher percentage of major adverse cardiovascular events (MACEs) (23.7%), all-cause death (18.3%) and cardiovascular (CV) death (9.4%) in Quartile 4. In multivariate Cox regression analysis, D-dimer was demonstrated to be independently associated with MACEs, all-cause death and CV death. The prognostic value of D-dimer is still significant in subgroups of HbA1C <7% and ≥7%. In Kaplan–Meier analysis, higher D-dimer showed poorer prognosis in MACEs, all-cause death and CV death (all log rank p < 0.001). The area under the curve (AUC) by receiver operating characteristic (ROC) curve analysis is 0.609 for MACEs, 0.708 for all-cause death, 0.747 for CV death (p < 0.001). ConclusionThe present study demonstrated the independent predictive value of D-dimer for outcomes in DM patients with ACS. In addition, for the first time, we explored the prognostic value in different glucose control status.

Associations of D-Dimer with Computed Tomographic Lung Abnormalities, Serum Biomarkers of Lung Injury, and Forced Vital Capacity: MESA Lung Study.

Rationale: The coagulation cascade may play a role in the pathogenesis of interstitial lung disease through increased production of thrombin and fibrin deposition. Whether circulating coagulation cascade factors are linked to lung inflammation and scarring among community-dwelling adults is unknown. Objectives: To test the hypothesis that higher baseline D-dimer concentrations are associated with markers of early lung injury and scarring. Methods: Using the MESA (Multi-Ethnic Study of Atherosclerosis) cohort (n = 6,814), we examined associations of baseline D-dimer concentrations with high attenuation areas from examination 1 (2000-2002; n = 6,184) and interstitial lung abnormalities from examination 5 computed tomographic (CT) scans (2010-2012; n = 2,227), and serum MMP-7 (matrix metalloproteinase-7) and SP-A (surfactant protein-A) from examination 1 (n = 1,098). We examined longitudinal change in forced vital capacity (FVC) from examinations 3-6 (2004-2018, n = 3,562). We used linear logistic regression and linear mixed models to examine associations and adjust for potential confounders. Results: The mean (standard deviation) age of the cohort was 62 (10) years, and the D-dimer concentration was 0.35 (0.69) ug/ml. For every 10% increase in D-dimer concentration, there was an increase in high attenuation area percentage of 0.27 (95% confidence interval (CI), 0.08-0.47) after adjustment for covariates. Associations were stronger among those older than 65 years (P values for interaction < 0.001). A 10% increase in D-dimer concentration was associated with an odds ratio of 1.05 for interstitial lung abnormalities (95% CI, 0.99-1.11). Higher D-dimer concentrations were associated with higher serum MMP-7 and a faster decline in FVC. D-dimer was not associated with SP-A. Conclusions: Higher D-dimer concentrations were associated with a greater burden of lung parenchymal abnormalities detected on CT scan, MMP-7, and FVC decline among community-dwelling adults.

The association of antenatal D-dimer and fibrinogen with postpartum hemorrhage and intrauterine growth restriction in preeclampsia

BackgroundD-dimer and fibrinogen were verified to be altered in preeclampsia. This study was to evaluate the associations of D-dimer and fibrinogen plasma levels with postpartum hemorrhage or intrauterine growth restriction in preeclamptic women.MethodsThis was a retrospective study that recruited 278 preeclamptic women with singleton pregnancy from January 2016 to December 2019. Patients were allocated into five groups: mild preeclampsia (mPE) (n=68), mild preeclampsia with postpartum hemorrhage (mPE+PPH) (n=13), severe preeclampsia (sPE) (n=112), severe preeclampsia with postpartum hemorrhage (sPE+PPH) (n=17) and severe preeclampsia with intrauterine growth restriction (sPE+IUGR) (n=68). The antenatal D-dimer and fibrinogen plasma levels were analyzed among the groups. Logistic regression was used to determine the correlation between serum indexes and PPH or IUGR in preeclampsia.ResultsThe antenatal D-dimer plasma levels were significantly higher in the sPE+PPH group than that in the sPE group (2.02 μg/ml versus 1.37 μg/ml, P = 0.001), but there was no difference in fibrinogen. Elevated D-dimer was associated with PPH among severe preeclamptic women (adjusted odds ratio (aOR) [95% CI]: 3.093 [1.527-6.264], P = 0.002). No differences in D-dimer and fibrinogen were found between the mPE and mPE+PPH groups or between the sPE and sPE+IUGR groups.ConclusionsElevated antenatal plasma D-dimer level may be associated with postpartum hemorrhage in severe preeclampsia, but not with intrauterine growth restriction. Future prospective clinical trials are needed to investigate the predictive value of D-dimer in postpartum hemorrhage in severe preeclampsia.

Associations of D-Dimer on Admission and Clinical Features of COVID-19 Patients: A Systematic Review, Meta-Analysis, and Meta-Regression.

BackgroundDynamic D-dimer level is a key biomarker for the severity and mortality of COVID-19 (coronavirus disease 2019). How aberrant fibrinolysis influences the clinical progression of COVID-19 presents a clinicopathological dilemma challenging intensivists.MethodsWe performed meta-analysis and meta regression to analyze the associations of plasma D-dimer with 106 clinical variables to identify a panoramic view of the derangements of fibrinolysis in 14,862 patients of 42 studies. There were no limitations of age, gender, race, and country. Raw data of each group were extracted separately by two investigators. Individual data of case series, median and interquartile range, and ranges of median or mean were converted to SDM (standard deviation of mean).FindingsThe weighted mean difference of D-dimer was 0.97 µg/mL (95% CI 0.65, 1.29) between mild and severe groups, as shown by meta-analysis. Publication bias was significant. Meta-regression identified 58 of 106 clinical variables were associated with plasma D-dimer levels. Of these, 11 readouts were negatively related to the level of plasma D-dimer. Further, age and gender were confounding factors. There were 22 variables independently correlated with the D-dimer level, including respiratory rate, dyspnea plasma K+, glucose, SpO2, BUN (blood urea nitrogen), bilirubin, ALT (alanine aminotransferase), AST (aspartate aminotransferase), systolic blood pressure, and CK (creatine kinase).InterpretationThese findings support elevated D-dimer as an independent predictor for both mortality and complications. The identified D-dimer-associated clinical variables draw a landscape integrating the aggregate effects of systemically suppressive and pulmonary hyperactive derangements of fibrinolysis, and the D-dimer-associated clinical biomarkers, and conceptually parameters could be combined for risk stratification, potentially for tracking thrombolytic therapy or alternative interventions.

Association of D-dimer and Fibrinogen With Hypercoagulability in COVID-19 Requiring Extracorporeal Membrane Oxygenation.

Background:D-dimer concentration has been used by institutions to identify candidates for intensified anticoagulant treatment for venous thromboembolism prevention and for the mitigation of the microthrombotic complications associated with COVID-19. Thromboelastography (TEG) maximum amplitude (MA) has been validated as a marker of hypercoagulability and MA ≥68 mm has been utilized as a marker of hypercoagulability in other conditions.Methods:The goal of this study was to evaluate the relationship between coagulation, inflammatory, and TEG parameters in patients with COVID-19 on extracorporeal membrane oxygenation (ECMO). We performed a single-center retrospective analysis of consecutive patients that received ECMO for the treatment of COVID-19. TEG, inflammatory, and coagulation markers were compared in patients with and without a thrombotic complication. Correlation tests were performed to identify the coagulation and inflammatory markers that best predict hypercoagulability as defined by an elevated TEG MA.Results:A total of 168 TEGs were available in 24 patients. C-reactive protein and fibrinogen were significantly higher in patients that developed a thrombotic event versus those that did not (P = 0.04 and P = 0.04 respectively). D-dimer was negatively correlated with TEG MA (P < 0.01), while fibrinogen was positively correlated (P < 0.01). A fibrinogen >441 mg/dL was found to have a sensitivity of 91.2% and specificity of 85.7% for the detection of MA ≥68 mm.Conclusions:In critically ill patients with COVID-19 treated with ECMO, D-dimer concentration had an inverse relationship with degree of hypercoagulability as measured by TEG MA. D-dimer elevation may potentially reflect hemostatic perturbation in patients on ECMO or the severity of COVID-19 related sepsis rather than designate patients likely to benefit from anticoagulation. Fibrinogen concentration may represent a more useful marker of hypercoagulability in this population.

Association of D-dimer and acute kidney injury associated with rhabdomyolysis in patients with exertional heatstroke: an over 10-year intensive care survey

Patients with rhabdomyolysis (RM) following exertional heatstroke (EHS) are often accompanied by dysfunction of coagulation and acute kidney injury (AKI). The purpose of this study was to investigate the relationship between D-dimer and AKI in patients with RM following EHS. A retrospective study was performed on patients with EHS admitted to the intensive care unit over 10-year. Data including baseline clinical information at admission, vital organ dysfunction, and 90-day mortality were collected. A total of 84 patients were finally included, of whom 41 (48.8%) had AKI. AKI patients had more severe organ injury and higher 90-day mortality (34.1 vs.0.0%, p < 0.001) than non-AKI patients. Multivariate logistic analysis showed that D-dimer (OR 1.3, 95% CI 1.1–1.7, p = 0.018) was an independent risk factor for AKI with RM following EHS. Curve fitting showed a curve relationship between D-dimer and AKI. Two-piecewise linear regression showed that D-dimer was associated with AKI in all populations (OR 1.3, 95% CI 1.2–1.5, p < 0.001) when D-dimer <10.0 mg/L, in RM group (OR 1.3, 95% CI 1.1–1.5, p < 0.001) when D-dimer >0.4 mg/L, in the non-RM group (OR 6.4, 95% CI 1.7–23.9, p = 0.005) when D-dimer <1.3 mg/L and D-dimer did not increase the incidence of AKI in the non-RM group when D-dimer >1.3 mg/L. AKI is a life-threatening complication of RM following EHS. D-dimer is associated with AKI in critically ill patients with EHS. The relationship between D-dimer and AKI depends on whether RM is present or not.

D-Dimer Improves Risk Prediction of Venous Thromboembolism in Patients with Multiple Myeloma

Introduction: Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with multiple myeloma (MM). Thromboprophylaxis is a safe and effective way to decrease VTE in other high-risk populations. Recently, a clinical prediction model was developed to identify patients with newly diagnosed MM starting chemotherapy at highest risk of VTE. The model, IMPEDE VTE, found the following clinical risk factors for VTE: immunomodulatory drugs, body mass index, recent pathologic fracture of the femur or hip, erythropoietin stimulating drugs, dexamethasone, doxorubicin, Asian ethnicity/race, history of VTE, tunneled line or central venous catheter, and existing use of aspirin or anticoagulation. External validation of the model has yielded a c-statistic for VTE risk prediction of 0.64 to 0.65. Laboratory parameters can predict VTE in some patients with cancer. Accordingly so, the addition of laboratory parameters to IMPEDE VTE has the ability to improve model performance. Thus, we sought to determine the association between soluble P-selectin and D-dimer with the development of VTE in patients with newly diagnosed MM starting chemotherapy. Methods: We identified 545 patients from the Washington University in St. Louis MM banking protocol, with available plasma from time of diagnosis (2007-2019). Thirty-eight cases of VTE were identified within 6 months following treatment initiation. An additional 137 patients were randomly selected as controls. D-dimer and soluble P-selectin ELISA assays were performed on the banked plasma by Eve Technologies, who was blinded to case vs. control status. Both assays were performed in duplicate and results averaged. All additional variables were collected through manual chart abstraction. IMPEDE VTE scores were calculated as we previously described (Sanfilippo et al.). The association of D-dimer and soluble P-selectin with VTE risk was assessed using Cox regression, adjusting for IMPEDE VTE score. Results: The median age of all 545 patients was 65 (range 32-79), 54% were male, and 85% were white. All patients received novel chemotherapy agents for first-line MM therapy and 66% underwent autologous stem cell transplant. Of the 38 cases with VTE, 20 patients had deep vein thrombosis, 17 had pulmonary emboli, and 1 patient had concurrent events. The median time from chemotherapy initiation to VTE was 51 days (range 4-193). The median IMPEDE VTE score was 5 (range -1 to 12). Each unit increase in IMPEDE VTE score was associated with a 21% increase in risk for VTE (HR 1.21; 95% CI 1.04-1.40; p = 0.01). Median D-dimer was 11,795 ng/mL (range 280-144,832). Each 1000 ng/mL unit increase in D-dimer was associated with a 2% increase risk for VTE after controlling for IMPEDE VTE score (aHR 1.02; 95% CI 1.01-1.04; p &amp;lt; 0.001). Patients in the highest quartile of D-dimer levels, above the 75th percentile, had a 2-fold increase in risk of VTE after adjusting for IMPEDE VTE score (aHR 2.04; 95% CI 1.03-4.02; p = 0.04). Median soluble P-selectin was 189 ng/ml (range 23-638). There was no association between soluble P-selectin level and VTE risk in patients with MM. Conclusions and Relevance: D-dimer is predictive of VTE in patients with MM starting chemotherapy. The combination of D-dimer and the IMPEDE VTE score can improve identification of patients at high risk of VTE and therefore allow for selection of primary thromboprophylaxis among patients with MM. Disclosures Sanfilippo: Bayer HealthCare Pharamceuticals: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Other: Travel Support for Investigator Meeting; Pfizer: Membership on an entity's Board of Directors or advisory committees; Covington &amp; Burling LLP: Consultancy; Luther &amp; Associates: Consultancy; Health Services Advisory Group: Consultancy; Amgen: Other: Trasfer of Value (food) during discussion of research.

Elevated D-dimer is associated with increased 28-day mortality in acute-on-chronic liver failure in China: a retrospective study

BackgroundAcute-on-chronic liver failure (ACLF) is a syndrome characterized by profound disrupted coagulation and fibrinolysis. Fibrinolytic marker D-dimer is increased in critically ill patients with cirrhosis which is associated with poorer prognosis. We aim to determine the potential association of D-dimer with the 28-day mortality in ACLF patients.MethodsIn a single center retrospective study performed in China, we collected data of 115 patients with ACLF from October 1, 2012 to December 31, 2016. We investigated correlations between D-dimer and other laboratory tests and prognostic scores. The relationship between D-dimer and 28-day mortality was explored by smoothing plot with an adjustment for potential confounders. Logistic regression analyses with crude and adjusted models were performed to explore the association of D-dimer with 28-day mortality in ACLF patients.ResultsIn ACLF patients, D-dimer at admission was correlated with all prognostic scores (MELD-Na: r = 0.385, P < 0.001; CLIF-C ADs: r = 0.443, P < 0.001; CLIF-C ACLFs: r = 0.375, P < 0.001). A nonlinear relation between D-dimer and 28-day mortality was found with a turning point at 6.5 mg/L FEU. D-dimer level was independently associated with 28-day mortality with an adjusted odds ratio of [1.4 (1.0–1.9), P = 0.030] as continuous variable and [10.3 (1.3, 81.5), P = 0.028] as a classified variable with the cut-off of 6.5 mg/L FEU. An elevated D-dimer within the following 10 days also tended to be associated with higher risk of 28-day mortality [OR: 27.5 (0.9, 814.9), P = 0.055].ConclusionsElevated D-dimer levels was associated with increased risk of 28-day mortality in patients with ACLF in China.

The Association of D-dimer and Spontaneous Hemorrhagic Ascites with Outcomes in Cirrhosis: a Retrospective Study.

Cirrhotic patients with hemorrhagic ascites have significant morbidity and mortality. This study aims to determine the relationship between D-dimer values and hemorrhagic ascites in cirrhotic patients and analyze its predictive value. This retrospective study screened 572 consecutive cirrhotic patients with ascites and hemorrhagic ascites (defined as red blood cells (RBC) in ascitic fluid ≥ 10,000/µL) during a 72-month period. The overall patient survival rate was measured by Kaplan-Meier analysis method. The relationship between D-dimer and hemorrhagic ascites was also examined. A multivariate Cox proportional hazard analysis was performed to assess the indepen-dent risk factors related to mortality. Both control group and hemorrhagic ascites patients had obvious hepatic dysfunction as determined by Model for End-Stage Liver Disease (MELD) scores of 6.37 ± 1.05 and 11.82 ± 2.86, respectively (p < 0.001). There was a higher prevalence of patients with significant ascites in those with spontaneous hemorrhagic ascites than in the control group (p = 0.003). There were significant differences in D-dimer levels between both groups (9.44 ± 5.11 vs. 26.83 ± 5.35, p < 0.001). Hemorrhagic ascites was significantly and positively correlated with D-dimer levels (r = 0.692, p < 0.0001). The area under the receiver operating characteristic (ROC) curve was 0.9838. Using Cox proportional hazard model for multivariate prognostic analysis, MELD, D-dimer and presence of spontaneous hemorrhagic ascites were independent predictors of 3-year mortality. Patients with hemorrhagic ascites had a significantly higher MELD score, D-dimer, and mortality than patients with ascites alone. D-dimer was associated with the appearance of hemorrhagic ascites and was found to be a marker of advanced liver disease and poor outcomes.

Association of D-dimer with the Risk of Mortality in Patients with Coronary Heart Disease

Association of D-dimer with the Risk of Mortality in Patients with Coronary Heart Disease

Association of D-dimer with Plaque Characteristics and Plasma Biomarkers of Oxidation-Specific Epitopes in Stable Subjects with Coronary Artery Disease.

D-dimer has emerged as a biomarker of cardiovascular event risk, yet pathophysiological factors associated with plasma D-dimer levels in stable coronary artery disease (CAD) subjects are poorly understood. In 106 stable CAD subjects undergoing intravascular ultrasound with virtual histology (IVUS-VH), we measured D-dimer, lipoprotein(a) (Lp(a)), plasminogen, biomarkers reflecting oxidation-specific epitopes (OSE) such as oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB), OxPL on plasminogen (OxPL-PLG), and autoantibodies to phosphorylcholine-BSA [PC-BSA] and a malondialdehyde [MDA] mimotope. In univariate analysis, D-dimer was positively associated with Lp(a), OxPL-apoB, OxPL-PLG, and coronary artery calcium, and inversely associated with autoantibodies to OSE and plaque fibrosis. D-dimer levels > 500ng/ml also showed positive association with plaque necrosis. After multivariate analysis, D-dimer remained significantly associated with Lp(a) and plaque calcium. While further studies are needed, results provide evidence that plasma D-dimer levels are associated with levels of OxPLs and IVUS-VH indices linked to plaque erosion and rupture.

Abstract 531: Association of D-Dimer With Oxidized Phospholipids, Antibodies to Oxidation-Specific Epitopes and Plaque Morphology in Coronary Artery Disease

Objective: Lp(a) is the prominent lipoprotein carrier of oxidized phospholipids (OxPLs) in plasma and OxPLs on Lp(a) are thought to contribute to its atherothrombotic effects. IgM antibodies to oxidation-specific epitopes (OSE) block proinflammatory properties of OxPLs and higher plasma levels in humans associate with reduced CAD and lower risk of cardiovascular (CV) events. Coronary thrombosis upon rupture of an unstable plaque leads to CV events. We hypothesize that plasma D-dimer, a marker of thrombosis, associates inversely with IgM antibodies to OSE and positively with OxPLs on apoB-100 (OxPL-apoB), Lp(a) and indices of unstable plaques as determined by VH-IVUS. Methods and Results: OxPL-apoB, Lp(a) and IgM to OSE (phosphocholine-BSA (PC-BSA) and a malondialdehyde (MDA) mimotope) were measured in 106 subjects with stable CAD undergoing angiography. The plasma D-dimer level was 367.8 ng/mL (range 78.3- 2098.8 ng/mL) and 37 subjects had D-dimer levels (mean ± SD; 918.52 ± 482.81 ng/mL) above the threshold for healthy subjects (&gt;500 ng/mL). D-dimer positively associated with OxPL-apoB (r=0.45, p=0.001) and Lp(a) (r=0.44, p=0.001; n=50) and inversely associated with IgM antibodies to PC-BSA and MDA mimotope (r=0.25, p=0.01 and r=0.20, p=0.04 respectively). Moreover, D-dimer associated inversely with plaque fibrosis (r=0.21, p=0.03), positively with coronary artery calcium (r=0.30, p=0.002) and trended to associate positively with necrosis (r=0.15, p=0.13) in univariate analysis. In multivariable analysis, significant association between D-dimer and calcium persisted while association with fibrosis was nearly significant (p=0.07). Notably, in subjects with D-dimer levels above 500 ng/mL, these associations were stronger (fibrosis; r=-0.45, p=0.006, calcium; r= 0.39, p=0.016, necrosis; r=0.45, p= 0.005). Conclusions: Our results suggest associations between Lp(a), OxPLs and potentially atheroprotective IgM antibodies to OSE and markers of thrombosis. While associations are modest and a larger study is needed, results raise the interesting possibility that plasma D-dimer may identify subjects prone to Lp(a)/OxPL-induced subclinical thrombosis, which may increase risk for future adverse events.

Abstract P249: Hemostatic Factors and Long-Term Risk of Peripheral Arterial Disease: The Atherosclerosis Risk in Communities (ARIC) Study

Background: A few cross-sectional studies have reported associations between hemostatic factors and peripheral arterial disease (PAD), but prospective data are largely lacking. Hypothesis: Plasma hemostatic factors are associated with incident PAD, independently of traditional atherosclerotic risk factors. Methods: In 14,071 men and women (age 45-64 years and 25.4% blacks) at visit 1 (1987-1989) of the ARIC Study, we investigated the associations of fibrinogen, Von Willebrand factor (VWF), factor VIII, factor VII, Antithrombin III (ATIII) with incidence of PAD (defined as hospitalizations with PAD diagnosis [ICD-9: 440.2x, 440.3, and 440.4] or leg revascularization [38.18, 39.25, 39.29 and 39.50]). We also explored associations of d-dimer measured at visit 3 (1993-1995) in 11,619 participants. Results: We identified 540 incident PAD during a median follow-up of 24.4 years. Fibrinogen, VWF, factor VIII, and d-dimer demonstrated positive dose-response relationships to incident PAD, independent of other risk factors (Table). In comparison with respective referent categories, significantly higher PAD risk was observed in the top two quintiles of fibrinogen, VWF, and d-dimer and the highest quintile of factor VIII. When fibrinogen, VWF, and factor VIII were modeled simultaneously (d-dimer was measured at a different visit), only fibrinogen and VWF remained significantly associated with PAD. Conclusion: Hemostatic factors, particularly fibrinogen and VWF (as well as d-dimer), were independently associated with future risk of PAD. Our findings suggest the pathophysiological involvement of hemostasis in the development of PAD and potential usefulness of those factors for classifying long-term risk of PAD.

Abstract P264: Association of D-dimer with Incident Cardiovascular Disease Events and F3 Gene Variants in African Americans: Results From the Jackson Heart Study

Plasma D-dimer, a fibrin degradation product, is a biomarker of both coagulation and fibrinolysis and a risk factor for both arterial and venous thrombosis. African Americans (AAs) have increased risk of thrombosis and higher levels of D-dimer as compared to European populations, but little is known about the genetic architecture of D-dimer in AAs. D-dimer was assessed in 4163 AAs from the Jackson Heart Study (mean age 55 years, 62.1% female). We hypothesized that D-dimer levels would associate with incident cardiovascular disease events and with both coding and noncoding genetic variants. Median (interquartile range) D-dimer in the cohort was 0.40 (0.26-0.64) μg/ml. D-dimer was associated with increased risk of coronary heart disease (hazard ratio (HR) per standard deviation (SD)=1.26, p=0.012), stroke (HR=1.27, p=0.018), heart failure (HR=1.33, p=0.001), and mortality (HR=1.25, p&lt;0.0001) in models adjusted for age, sex, BMI, current smoking, diabetes, hypertension, systolic blood pressure, and low-density lipoprotein cholesterol. Using data from the Affymetrix Genome-Wide Human SNP Array 6.0, imputation based on the 1000 Genomes project reference panel (Phase I, Version 3, March 2012 release) was completed using MACH 1.0 and minimac in 2709 participants with D-dimer. Associations were assessed using MACH2QTL v.1.13, with models adjusted for age, sex, and the first ten principal components for global ancestry calculated using EIGENSOFT. The most significant signal was for an intergenic locus near F3 (top variant rs2022030, p=5.71x10 -12 , minor allele frequency=10.6%, imputation r 2 =1). F3 codes for tissue factor, a necessary co-factor for factor VIIa in the initiation of the extrinsic blood coagulation pathway. The F3 locus had been previously associated with D-dimer levels in European populations but has not been reported for AAs. Data were also available from the Illumina HumanExome Beadchip, version 1.1, in 2502 individuals; single variant analyses and gene-based tests for nonsynonymous, splicing, and nonsense variants with a minor allele frequency &lt;5% were performed using RAREMETAL, adjusted for age, sex, and the first ten principal components. For single variant analyses, a nonsynonymous variant in GPRASP1 (G protein-coupled receptor associated sorting protein 1, rs145805077, p= 1.84x10 -7 , minor allele frequency=0.3%) was significantly associated with decreased D-dimer. No gene-based test result met the strict multiple comparison significance threshold; the top gene-based result with the sequence kernel association test (SKAT) was for six variants in PPM1M (protein phosphatase, Mg2+/Mn2+ dependent, 1M, p=6.09x10 -6 ). These results highlight D-dimer as an important predictor of cardiovascular disease risk in AAs and that levels of this biomarker are associated with the F3 locus.