High D-dimer Group Research Articles

The Prognostic Value of D-Dimer in Patients with Acute Myocardial Infarction: A Retrospective Longitudinal Cohort Study in Taiwan.

Serum D-dimer level has been associated with worsening outcomes in patients with acute myocardial infarction. This study aimed to explore the association between serum D-dimer level and clinical outcomes in Taiwanese patients with acute myocardial infarction. We analyzed Tri-Service General Hospital-Coronary Heart Disease registry data related to patients with acute myocardial infarction who were admitted between January 2014 and December 2018. A total of 748 patients were enrolled and categorized into high (≥ 495 ng/ml) and low (< 495 ng/ml) D-dimer groups. The primary endpoint was in-hospital mortality, and secondary endpoints were post-discharge mortality and post-discharge major adverse cardiovascular events. Overall, 139 patients died, with 77 from cardiovascular causes and 62 from non-cardiovascular causes. In-hospital mortality was higher in the high D-dimer group than in the low D-dimer group. Among the patients alive at discharge, those with a high D-dimer level had higher cardiovascular mortality and future major adverse cardiovascular events than those with a low D-dimer level. Multivariate Cox regression analysis revealed that higher serum D-dimer levels were significantly associated with higher risks of in-hospital mortality [hazard ratio (HR) = 1.11; 95% confidence interval (CI), 1.06-1.16, p < 0.001], subsequent cardiovascular mortality after discharge (HR = 1.15; 95% CI, 1.08-1.22, p < 0.001), and major adverse cardiovascular events (HR = 1.10; 95% CI, 1.04-1.16, p < 0.001). This is the first study in Taiwan to demonstrate that a higher baseline serum D-dimer level was independently associated with higher risks of in-hospital mortality, post-discharge mortality, and major adverse cardiovascular events in patients with acute myocardial infarction.

The Important Role of Preoperative D-Dimer in Constrictive Pericarditis.

The impact of coagulation indicators on postoperative outcomes of patients with constrictive pericarditis undergoing pericardiectomy has been poorly investigated. This study aimed to assess the prognostic role of preoperative coagulation indicators in these patients. We retrospectively included 158 patients with constrictive pericarditis undergoing pericardiectomy. The diagnostic values of coagulation indicators for postoperative complications were evaluated by ROC curves. Patients were divided into two groups according to the cutoff value calculated by ROC curve. Postoperative outcomes were compared between the two groups. Logistic regression analysis was performed to identify risk factors of postoperative complications. ROC curve showed that among different coagulation indicators, preoperative D-dimer (DD) level could effectively identify patients with postoperative complications (AUC 0.771, 95% CI 0.696-0.847, P < 0.001). Patients were divided into the low DD group and the high DD group. The comparison of postoperative outcomes suggested that high preoperative DD level was significantly associated with longer durations of vasoactive agents using (P = 0.018), intubation (P = 0.020), ICU stay (P = 0.008), chest drainage (P=0.004) and hospital stay (P = 0.002). Multivariable analysis showed that high preoperative DD level was the independent risk factor of postoperative complications (OR 6.892, 95% CI 2.604-18.235, P < 0.001). High preoperative DD level was significantly linked to poor postoperative outcomes and could provide an effective prediction ability for postoperative complications in patients with constrictive pericarditis.

Predictive value of d-dimer for plaque rupture, thrombus and worse clinical outcomes in acute coronary syndrome from TACTICS registry

Abstract Background Acute coronary syndrome (ACS) mainly occurs by the rupture of lipid plaques with platelet aggregation. D-dimer (DD) is a primary degradation product and circulating marker of fibrinolysis. The use of DD helps to diagnose thrombosis. The serum DD level may indicate a thrombus within coronary artery in patients with ACS. Purpose The present study determined the association of serum DD level on admission with a thrombus within culprit lesion and ACS mechanism assessed by optical coherence tomography (OCT), and clinical outcomes. Methods and Results Tokyo/ Kanagawa/ Chiba/ Shizuoka/ Ibaraki active OCT applications for ACS (TACTICS) registry includes 695 consecutive ACS patients who underwent emergent PCI with OCT guidance. Of those, the information of serum DD level was available in 653 cases. Those patients were divided into two groups according to serum DD level on admission: high DD group(≧0.73 μg/ml, n= 328) and low DD group(＜0.73 μg/ml, n= 325). Comparison of type of plaque morphology and thrombus are shown in Figure. ACS patients with high DD level had poor long-term outcomes. Conclusion High serum DD level was associated with red-thrombus, plaque rupture, and worse prognosis in ACS. The simple test of DD may give us useful information in clinical practice for ACS.

The Prognostic Value of Prognostic Nutritional Index Combined with D-dimer in Patients with Diffuse Large B-Cell Lymphoma

To explore the effects of prognostic nutritional index (PNI) combined with D-dimer on the prognosis of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The clinical data of 73 DLBCL patients at initial diagnosis were retrospectively evaluated, and the optimal cut-off point of PNI and D-dimer were determined by ROC curve. The overall survival (OS) rate and progression-free survival (PFS) rate in different subgroups were compared using Kaplan-Meier survival curves. Univariate and multivariate Cox regression analysis was performed to identify the factors associated with OS. Compared with the low PNI group (PNI<44.775), the high PNI group (PNI≥44.775) had better OS (P =0.022) and PFS (P =0.029), the 2-year OS rates of the two groups were 55.6% and 78.3% respectively (P =0.041). Compared with the high D-dimer group (D-dimer≥0.835), the low D-dimer group (D-dimer<0.835) had better OS (P <0.001) and PFS (P <0.001), the 2-year OS rates of the two groups were 51.4% and 86.8% respectively (P =0.001). Meanwhile, patients in the high PNI+ low D-dimer group had better OS (P =0.003) and PFS (P <0.001) than the other three groups, the 2-year OS rate was statistically different from the other three groups (P <0.05). The multivariate analysis revealed that NCCN-IPI (HR =2.083, 95%CI : 1.034-4.196, P =0.040), PNI (HR =0.267, 95%CI : 0.076-0.940, P =0.040) and PNI+D-dimer (HR =9.082, 95%CI : 1.329-62.079, P =0.024) were the independent risk factors affecting OS in patients with DLBCL. Subgroup analysis showed that PNI, D-dimer, and PNI combined with D-dimer could improve the prognostic stratification in low and low-intermediate risk DLBCL patients. High PNI, low D-dimer and combination of high PNI and low D-dimer at initial diagnosis suggest a better prognosis in DLBCL patients.

Higher D-dimer and activated partial thromboplastin time are poor prognostic factors in patients with peritoneal dialysis-related peritonitis.

Coagulation system dysfunction is associated with adverse outcomes of peritoneal dialysis (PD) and bacterial infection. We investigated the association between coagulation system and treatment failure of peritoneal dialysis-related peritonitis (PDRP). We collected records of patients aged ≥18 years with PDRP. PDRP episodes were divided into: shortened activated partial thromboplastin time (APTT) group and prolonged APTT group, low D-dimer (DD) group and high DD group. The baseline characteristics of the groups were collected and compared. The association between APTT, DD and treatment failure of PDRP was analyzed using logistic regression analysis. Thirty episodes of treatment failure were observed in 110 episodes of PDRP in our study. After adjusting for variables, prolonged APTT (OR = 1.166 [1.049-1.296], p = 0.004) or high level of DD (OR = 1.374 [1.057-1.787], p = 0.017) was associated with treatment failure of PDRP. Prolonged baseline APTT or high level of DD increased the risk of treatment failure of PDRP.

Relationship between baseline D-dimer and prognosis in Japanese patients with venous thromboembolism: Insights from the J'xactly study.

D-dimer is a biomarker of fibrin production and degradation, and changes in D-dimer concentration suggest fibrin clot formation, which is associated with thromboembolism and hypercoagulable states. Thus, an elevated D-dimer concentration could be a useful prognostic predictor for patients with venous thromboembolism (VTE). In this subanalysis of the J'xactly study, a prospective multicenter study conducted in Japan, we examined the clinical outcomes of 949 patients with VTE stratified by baseline D-dimer concentration. The median D-dimer concentration was 7.6 μg/ml (low D-dimer group: <7.6 μg/ml [n = 473, 49.8%]; high D-dimer group: ≥7.6 μg/ml [n = 476, 50.2%]). The mean age of the patients was 68 years, and 386 patients (40.7%) were male. Compared with the low D-dimer group, the high D-dimer group had more frequent pulmonary embolism with or without deep vein thrombosis (DVT), proximal DVT, atrial fibrillation, or diabetes mellitus, and underwent intensive treatment with 30 mg/day rivaroxaban. The incidence of composite clinically relevant events (recurrence or exacerbation of symptomatic VTE, acute coronary syndrome [ACS], ischemic stroke, death from any cause, or major bleeding) was higher in the high D-dimer group than in the low D-dimer group (11.1% vs. 7.5% per patient-year; hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; p = 0.025). There was no significant difference between the high and low D-dimer groups in the incidence of VTE (2.8% vs. 2.5% per patient-year, respectively; p = 0.788), ACS (0.4% per patient-year vs. not observed, respectively; p = 0.078), or major bleeding (4.0% vs. 2.1% per patient-year, respectively; p = 0.087), but there was a significant difference in the incidence of ischemic stroke (1.0% per patient-year vs. not observed, respectively; p = 0.004). Elevated D-dimer concentration may be an important prognostic predictor in Japanese patients with VTE.Clinical Trial Registration: UMIN CTR, UMIN000025072 (https://www.umin.ac.jp/ctr/index.htm).

Association of D-dimer Level with Renal Parameters and Cardiovascular Events in Type 2 Diabetes Mellitus: A Retrospective Cohort Study

Introduction: D-dimer is a biomarker that can detect early stages of renal and cardiovascular dysfunction in Type 2 Diabetes Mellitus (T2DM). It serves as a key indicator and is readily available in laboratory settings, along with other risk factors. Aim: To investigate the association between D-dimer levels and renal parameters, as well as cardiovascular events, among T2DM subjects. Materials and Methods: This retrospective cohort study was conducted at Visnagar’s Nootan Medical College and Research Centre, Visnagar, Gujarat, India, involving subjects who visited the centre for health checks between September 2021 and December 2022. Screening was performed on all adult individuals with T2DM. Clinical records of 550 consecutive T2DM patients, aged between 18 and 80 years, receiving care at the centre were analysed. After applying exclusion criteria, 155 patients with T2DM diagnosis were enrolled. Parameters such as cystatin C, D-dimer, serum creatinine, urea, estimated Glomerular Filtration Rate (eGFR), and albuminuria were evaluated in all subjects. Bivariate logistic regression analysis was conducted to determine whether renal indicators are associated with high D-dimer levels, generating an odds ratio. Multivariate logistic regression analysis was then performed, correcting for sex and age, to determine which kidney indicators are linked to high D-dimer levels. Results: A total of 155 participants were included in this study, and were divided into high and low D-dimer groups. The mean ages of the low and high D-dimer groups were 40±13 years and 55±10 years, respectively. Compared to the low D-dimer group, the high D-dimer group had a higher frequency of males (p-value &lt;0.001). Patients with high D-dimer levels exhibited significantly increased levels of HbA1c, creatinine, urea, cystatin C, and UAE compared to patients with low D-dimer levels (p-value=0.001, p-value=0.001, p-value &lt;0.001, p-value &lt;0.001, and p-value=0.001, respectively). Conclusion: D-dimer may be beneficial in identifying patients with early-stage diabetic kidney disease, thereby promoting the early adoption of renal and cardioprotective therapy. Additionally, elevated D-dimer levels are associated with an increased risk of cardiovascular disease.

Prognostic Role of Preoperative D-dimer Levels in Patients With Stage I-III Colorectal Cancer.

As D-dimer levels have been reported to reflect cancer activity, preoperative D-dimer levels may serve as a prognostic marker in patients with colorectal cancer. The aim of this study was to evaluate the prognostic significance of preoperative D-dimer levels in patients with stage I-III colorectal cancer who underwent curative surgery. A total of 264 patients who underwent curative surgery for stage I-III colorectal cancer between January 2015 and December 2019 were enrolled in this study. The median preoperative D-dimer level was 0.8 μg/ml (range=0.4-42.5 μg/ml). Based on the results of a receiver operating characteristic curve analysis, we set 1.45 as the cut-off value and classified patients into the low (n=215) and high D-dimer (n=49) groups. The high D-dimer group had significantly lower relapse-free and overall survival in comparison to the low D-dimer group (p<0.0001, p<0.0001, respectively). Preoperative D-dimer levels can serve as a prognostic marker for stage I-III colorectal cancer.

Prognostic value of plasma D-dimer levels in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: a retrospective study.

Plasma D-dimer is of great significance for the clinical exclusion of tumor-related thrombosis. Previous studies have shown its predictive role in non-small cell lung cancer (NSCLC) treated with chemotherapy. However, whether pretreatment D-dimer could predict the efficacy and prognosis in NSCLC patients treated with immune checkpoint inhibitors (ICIs) remains unclear. Advanced NSCLC patients treated with ICIs at the Chinese PLA General Hospital between January 2015 and March 2019 were enrolled. Patients were divided into a pretreatment normal D-dimer group (≤0.5 µg/mL) and high D-dimer group (>0.5 µg/mL). Optimization-based approach was applied to balance baseline covariates between the 2 groups, including age, sex, histological type, smoking history, stage, Eastern Cooperative Oncology Group Performance Status (ECOG PS), lines of treatment, ICI drugs, brain metastasis, treatment type, and D-dimer levels. Kaplan-Meier analysis and Cox proportional hazards model were used for analyzing survival data, including progression-free survival (PFS, the time from initial ICI treatment to PD or death), overall survival (OS, the time between initial ICI treatment and death), and hazard ratio (HR). Follow-up of all patients was performed by searching electronic medical records and counseling telephone. The follow-up cut-off date was July 6, 2020. This study included 277 advanced NSCLC patients. Among the enrolled patients, 23.1% were female, 64.6% had non-squamous cell lung cancer, and 79.4% were stage IV. Univariate and multivariate analysis showed that pretreatment high D-dimer levels were independently associated with shortened PFS and OS (P<0.01). Subgroup analysis confirmed that pretreatment high D-dimer levels were associated with poor prognosis in most subsets. After balancing baseline covariates between the high D-dimer group and normal D-dimer group, the results indicated that patients with pretreatment high D-dimer levels had significantly shorter PFS [median: 6.4 vs. 11.5 months; HR, 1.70; 95% confidence ratio (CI): 1.25-2.37; P<0.001] and OS (median: 12.7 vs. 30.4 months; HR, 2.29; 95% CI: 1.54-3.41; P<0.001) than those with pretreatment normal D-dimer levels. Pretreatment plasma D-dimer could serve as a convenient prognostic biomarker for advanced NSCLC patients receiving ICI treatment. Patients with pretreatment high D-dimer levels may have poor PFS and OS.

Significance of D-Dimer in Acute Ischemic Stroke Patients With Large Vessel Occlusion Accompanied by Active Cancer

BackgroundThis study aimed to investigate clinical outcome predictors of acute stroke patients with large vessel occlusion and active cancer and validate the significance of D-dimer levels for endovascular thrombectomy decisions.MethodsWe analyzed a prospectively collected hospital-based stroke registry to determine clinical EVT outcomes of acute stroke patients within 24 h with following criteria: age ≥18 years, NIHSS ≥6, and internal carotid artery or middle cerebral artery lesion. All patients were classified into EVT and non-EVT groups. Patients were divided into two groups by initial D-dimer level. We explored variables potentially associated with successful recanalization as well as 3-month functional outcomes and mortality rates.ResultsAmong 68 patients, 36 were treated with EVT, with successful recanalization in 55.6%. The low D-dimer group showed a higher rate of successful recanalization and favorable outcome than the high D-dimer group. The mortality rate was higher in the high D-dimer group. No EVT and high D-dimer level were independent predictors of mortality, whereas lesion volume and low D-dimer level were independently associated with favorable outcomes.ConclusionsD-dimer level is a prognostic factor in acute LVO stroke patients with active cancer, and its high value for EVT decisions provisionally supports its testing in this patient population.

D-Dimer Is a Predictive Factor of Cancer Therapeutics-Related Cardiac Dysfunction in Patients Treated With Cardiotoxic Chemotherapy

BackgroundD-dimer is a sensitive biomarker for cancer-associated thrombosis, but little is known about its significance on cancer therapeutics-related cardiac dysfunction (CTRCD).MethodsConsecutive 169 patients planned for cardiotoxic chemotherapy were enrolled and followed up for 12 months. All patients underwent echocardiography and blood test at baseline and at 3-, 6-, and 12 months.ResultsThe patients were divided into two groups based on the level of D-dimer (>1.65 μg/ml or ≦ 1.65 μg/ml) at baseline before chemotherapy: high D-dimer group (n = 37) and low D-dimer group (n = 132). Left ventricular ejection fraction (LVEF) decreased at 3- and 6 months after chemotherapy in high D-dimer group [baseline, 65.2% (62.8–71.4%); 3 months, 62.9% (59.0–67.7%); 6 months, 63.1% (60.0–67.1%); 12 months, 63.3% (58.8–66.0%), p = 0.03], but no change was observed in low D-dimer group. The occurrence of CTRCD within the 12-month follow-up period was higher in the high D-dimer group than in the low D-dimer group (16.2 vs. 4.5%, p = 0.0146). Multivariable logistic regression analysis revealed that high D-dimer level at baseline was an independent predictor of the development of CTRCD [odds ratio 3.93, 95% CI (1.00–15.82), p = 0.047].ConclusionWe should pay more attention to elevated D-dimer levels not only as a sign of cancer-associated thrombosis but also the future occurrence of CTRCD.

Predictive Role of the D-Dimer Level in Acute Kidney Injury in Living Donor Liver Transplantation: A Retrospective Observational Cohort Study.

This study aimed to determine the association between serum D-dimer levels and the risk of acute kidney injury (AKI) in patients undergoing living donor liver transplantation (LDLT). Clinical data of 675 patients undergoing LDLT were retrospectively analyzed. The exclusion criteria included a history of kidney dysfunction, emergency cases, and missing data. The final study population of 617 patients was divided into the normal and high D-dimer groups (cutoff: 0.5 mg/L). After LDLT, 145 patients (23.5%) developed AKI. A high D-dimer level (>0.5 mg/L) was an independent predictor of postoperative development of AKI in the multivariate analysis when combined with diabetes mellitus [DM], platelet count, and hourly urine output. AKI was significantly higher in the high D-dimer group than in the normal D-dimer group (odds ratio [OR], 2.792; 95% confidence interval [CI], 1.227–6.353). Patients with a high D-dimer exhibited a higher incidence of early allograft dysfunction, longer intensive care unit stay, and a higher mortality rate. These results could improve the risk stratification of postoperative AKI development by encouraging the determination of preoperative D-dimer levels in patients undergoing LDLT.

D-Dimer as a Prognostic Factor in a Tertiary Center Intensive Coronary Care Unit.

IntroductionD-dimer is a small protein fragment produced during fibrinolysis. High D-dimer levels were shown to have prognostic impact in critically ill patients. Nevertheless, data regarding D-dimer's prognostic impact among tertiary care intensive coronary care unit (ICCU) patients is scarce.Material and methodAll patients admitted to the ICCU between 1-12/2020 were prospectively included. Based on admission D-dimer level, patients were categorized into low and high D-dimer groups (< 500 ng/ml and ≥ 500 ng/ml) and also to age-adjusted D-dimer cutoff (500 ng/ml for ages ≤ 50 years old and age*10 for ages>50 years old).Results and discussionA total of 959 consecutive patients were included, including 296 (27.4%) and 663 (61.3%) patients with low and high D-Dimer levels, respectively. Patients with high D-dimer level were older compared with patients with low D-dimer level (age 70.4 ± 15 and 59 ± 13 years, p = 0.004) and had more comorbidities. The most common primary diagnosis on admission among the low D-dimer group was acute coronary syndrome (ACS) (74.3%), while in the high D-dimer group it was a combination of ACS (33.6%), cardiac structural interventions (26.7%) and various arrhythmias (21.1%). High D-dimer levels were associated with increased mortality rate, even after adjustment for age, gender, comorbidities and left ventricular ejection fraction (LVEF). High D-dimer levels were independently associated with increased overall 1-year mortality rate (HR = 5.8; 95% CI; 1.7-19.1; p = 0.004).ConclusionElevated D-dimer levels on admission in ICCU patients is an independently poor prognostic factor for in-hospital morbidity and 1-year overall mortality rate following hospitalization.

COT-9 Prognostic impact of hypercoagulation in glioblastoma and molecular mechanism thereof

Introduction: Pathological features of glioblastoma include intravascular thrombosis, suggesting that the thrombus formation in tumor microenvironment contributes to progression of gliomas. Meanwhile, glioblastoma has been known to be high risk malignant tumor for venous thromboembolism, however, it remains unclear how the coagulation-fibrinolysis system is disrupted, which essentially grow within the cranium in a localized manner, and how the disruption contributes to the malignant transformation. Methods: Total 64 patients with glioblastoma between January 2014 and April 2021 who underwent a D-dimer test before the therapeutic intervention were divided into two groups: the high D-dimer group (D-dimer level >3.0μg/ml) and the low D-dimer group (D-dimer level <3.0μg/ml). We compared the two groups in the maximum gadolinium-enhanced MRI lesions, MIB-1 index, and gene abnormalities (IDH mutation, TERT promoter mutation, and MGMT promotor methylation). The progression-free survival (PFS) and overall survival were analyzed using the Kaplan-Meier method. Furthermore, in 23 patients who underwent a D-dimer test at recurrence, the time to death after recurrence was analyzed. Results: The PFS in high D-dimer group was significantly shorter than that in the low D-dimer group (log-rank p = 0.0075). The D-dimer increase at the time of recurrence significantly correlated with the decrease in post-recurrence survival duration (log-rank p = 0.0226). Moreover, the gadolinium-enhanced lesions in the high D-dimer group were significantly larger. Conclusion: The Pre-intervention D-dimer levels and PFS suggest that glioblastoma-induced systemic enhancement of the coagulation-fibrinolysis system plays a role in the malignant transformation. The D-dimer increase during the treatment was found to be a predictor of poor prognosis after recurrence. Furthermore, the MRI findings revealed a correlation between the D-dimer increase and the size of intratumoral necrosis. Meanwhile, no correlation with the MIB-1 index was found, suggesting that the mechanism of malignant transformation by hypercoagulation differ from enhanced cell proliferation.

Primary Percutaneous Coronary Intervention in Patients With Type 2 Diabetes With Late/Very Late Stent Thrombosis and de novo Lesions: A Single-Center Observational Cohort Study of Clinical Outcomes and Influencing Factors.

Background: This study compared differences in the risk factors and clinical outcomes of primary percutaneous coronary intervention (PCI) in type 2 diabetes mellitus (DM) and non-DM patients with de novo lesions (DNLs) and late or very late stent thrombosis (LST/VLST).Methods: We used angiography to screen 4,151 patients with acute coronary syndrome for DNL and LST/VLST lesions. Overall, 3,941 patients were included in the analysis and were allocated to the DM (n = 1,286) or non-DM (n = 2,665) group at admission. The primary endpoint was a composite of major adverse cardiovascular events (MACEs), defined as death, myocardial infarction, revascularization, and ischemic stroke, within a median follow-up period of 698 days.Results: In the group with a total white blood cell count >10 × 109/L (P = 0.004), a neutral granular cell count >7 × 109/L (P = 0.030), and neutrophil–lymphocyte ratio >1.5 (P = 0.041), revascularization was better for DNL than for LST/VLST lesions. Among DM patients with DNLs, each unit increase in age was associated with a 53.6% increase in the risk of MACEs [hazard ratio (HR): 1.536, 95% confidence interval (CI), 1.300–1.815, P < 0.0001]. Older age (≥65 years) was associated with a significantly greater risk of MACEs (P < 0.0001). Furthermore, each standard deviation (SD) increase in the level of peak white blood cell counts was associated with a 50.1% increase in the risk of MACEs (HR, 1.501; 95% CI, 1.208–1.864; P = 0.0002). When stratifying the DM population with DNLs according to the D-dimer baseline and peak levels <0.5 vs. ≥0.5 mg/L, the high D-dimer group at baseline had a 2.066-fold higher risk of MACEs (P < 0.0001), and the high peak level D-dimer group had a 1.877-fold higher risk of MACEs (P = 0.001) compared to the low-level groups. Among DM patients with LST/VLST, each unit increase in age was associated with a 75.9% increase in the risk of MACEs (HR: 1.759, 95% CI, 1.052–2.940, P = 0.032). Furthermore, for each SD increase in the peak D-dimer level, the risk of MACEs increased by 59.7% (HR, 1.597; 95% CI, 1.110–2.295; P = 0.041).Conclusion: Following successful primary PCI, the measurement of baseline and peak D-dimer values may help identify individuals at high cardiovascular risk. This suggests a potential benefit of lowering D-dimer levels among T2DM patients with DNL. Furthermore, age and the peak D-dimer values may facilitate the risk stratification of T2DM patients with LST/VLST.

Prognostic Value of D-dimer in patients with acute coronary syndrome treated by percutaneous coronary intervention: a retrospective cohort study

BackgroundAssociations between D-dimer and outcomes of patients with acute coronary syndromes (ACS) remain controversial. This study aimed to investigate the prognostic value of D-dimer in ACS patients treated by percutaneous coronary intervention (PCI).MethodsIn this observational study, 3972 consecutive patients with ACS treated by PCI were retrospectively recruited. The X-tile program was used to determine the optimal D-dimer thresholds for risk stratifications. Cox regression with multiple adjustments was used for outcome analysis. Restricted cubic spline (RCS) analysis was performed to assess the dose-response association between D-dimer and outcomes. The C-index was calculated to evaluate the additional prognostic value of D-dimer when added to clinical risk factors and commonly used clinical risk scores, with internal validations using bootstrapping methods. The primary outcome was all-cause death.ResultsDuring a median follow-up of 720 days, 225 deaths occurred. Based on the thresholds generated by X-tile, ACS-PCI patients with median (420–1150 ng/mL, hazard ratio [HR]: 1.58, 95 % confidence interval [CI]: 1.14–2.20, P = 0.007) and high (≥ 1150 ng/mL, HR: 1.98, 95 % CI: 1.36–2.89, P < 0.001) levels of D-dimer showed substantially higher risk of death compared to those with low D-dimer (< 420 ng/mL). RCS analysis depicted a constant relation between D-dimer and various outcomes. The addition of D-dimer levels significantly improved risk predictions for all-cause death when combined with the fully adjusted models (C-index: 0.853 vs. 0.845, P difference = 0.021), the GRACE score (C-index: 0.826 vs. 0.814, P difference = 0.027), and the TIMI score (C-index: 0.804 vs. 0.776, P difference < 0.001). The predicted mortality at the median follow-up (two years) was 1.7 %, 5.2 %, and 10.9 % for patients with low, median, and high D-dimer, respectively, which was well matched with the observed mortality (low D-dimer group: 1.2 %, median D-dimer group: 5.2 %, and high D-dimer group: 12.6 %).ConclusionsFor ACS patients treated by PCI, D-dimer level was an independent predictor for adverse outcomes, and provided additional prognostic value when combined with clinical risk factors and risk scores. Risk stratifications based on D-dimer was plausible to differentiate ACS-PCI patients with higher risk of death.

D-dimer predicts poor hospitalisation outcomes in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis.

The in-hospital mortality rate among patients with antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) is high. Unfortunately, there is no reliable prognostic biomarker. This study aimed to investigate whether elevated D-dimer levels can predict hospitalisation outcomes among patients with AAV. We performed a retrospective analysis at a tertiary medical centre in Seoul, South Korea, between 2005 and 2019. Patients with AAV requiring hospitalisation, whose D-dimer levels were available within one week of hospitalisation, were included; patients with known alternative reasons for elevated D-dimer were excluded. Death and intensive care unit requirements were defined as adverse outcomes. In total, 61 AAV patients with a total of 100 episodes of hospitalisation were included. Median D-dimer levels were significantly higher in patients with adverse outcomes than in those without adverse outcomes (1.84 vs. 0.42 mg/dL; p=0.006). Consistently, the incidence of the adverse outcomes was significantly higher in the high D-dimer group (≥0.699 mg/dL; n = 40) than in the low D-dimer group (<0.699 mg/dL; n = 60) (35% vs. 10%; p=0.002). Multivariate logistic regression analysis revealed that a high D-dimer level was a significant risk factor for adverse outcomes (hazard ratio, 4.852; 95% confidence interval, 1.320-17.833; p=0.017). Kaplan-Meier survival analysis revealed that the high D-dimer group was associated with more 30-day in-hospital adverse outcomes than the low D-dimer group (p=0.008). High D-dimer levels on admission are significantly associated with adverse outcomes among patients with AAV.

Abstract 13441: D-dimmer is a Predictor of Cancer Therapeutics-related Cardiac Dysfunction in Patients Treated With Cardiotoxic Chemotherapy

Background: D-dimer is a sensitive biomarker for cancer-associated thrombosis, but little is known about its significance on cancer therapeutics-related cardiac dysfunction (CTRCD). Methods and Results: Consequtive 202 patients planned for cardiotoxic chemotherapy (anthracyclines, monoclonal antibodies, tyrosine kinase inhibitors, and proteasome inhibitors) were enrolled and followed up for 12 months. Cancer types were as follows: breast cancer (n=112), lymphoma (n=37), ovarian or uterine cancer (n=18), leukemia (n=13), multiple myeloma (n=6), bone cancer (n=4), and others (n=12). All patients underwent echocardiography and blood test at baseline, 3-month, 6-month, and 12-month. The patients were divided into 2 groups based on the value of D-dimer (&gt;1.5 μg/ml or ≦1.5 μg/ml) at baseline before chemotherapy: High D-dimer group (n=52) and Low D-dimer group (n=150). At baseline, left ventricular ejection fraction (LVEF), left ventricular end-systolic volume index, and B-type natriuretic peptide levels were similar between two groups. Time-dependent decrease in LVEF was observed after chemotherapy in high D-dimer group (baseline, 66±5%; 3-month, 63±7%; 6-month, 62±7%; 12-month 62±6%; P=0.005, figure), but not in low D-dimer group. Time-dependent increase in troponin I was similarly observed after chemotherapy in both groups. The occurrence of CTRCD was higher in high D-dimer group than in low D-dimer group (11.5% vs. 4.0%, P=0.048). When we set the cut-off value of baseline D-dimer at 1.65 μg/ml from ROC analysis, sensitivity, specificity, and area under the curve to predict CTRCD were 50%, 77%, and 0.679, respectively. Multivariable logistic analysis revealed that baseline D-dimer was an independent factor to predict the decrease in LVEF more than 10% after cardiotoxic chemotherapy (odds ratio 1.210, 95% confidence interval [1.020-1.440], P=0.025). Conclusion: Baseline D-dimer is a pivotal parameter to predict CTRCD.

Abstract 221: Exosomal MicroRNAs Drive Tromboembolism in Covid-19

Introduction: Thromboembolic complications play a crucial role in the clinical outcome of COVID-19. Emerging evidence has shown that exosomal microRNAs (miRNAs) are functionally involved in several pathologic processes. Methods: To test the hypothesis that exosomal miRNAs are a key determinant of thrombosis in COVID-19, we enrolled 26 COVID-19 patients. The study was approved by the local Ethical Committees. Circulating exosomes were isolated as we previously described and validated by our group and levels of exosomal miRNAs, from a custom panel of miRNAs, were quantified by RT-qPCR and normalized to the expression of U18. Results: We divided our population in two groups based on serum D-dimer level on admission, using a previously published cut-off of 3 μg/ml. No significant differences in the main clinical characteristics were noted comparing patients with low (n=11) vs high (n=15) D-Dimer. Strikingly, we found that exosomal miR-424 was significantly upregulated whereas exosomal miR-103a, miR-145, and miR-885 were significantly downregulated in patients in the high D-dimer group compared to patients in the low D-Dimer group ( p&lt;0.0001 ). Regression analysis confirmed these findings. Mechanistically, Tissue Factor (TF) was identified as a direct target of miR-145, while miR-885 targets the von Willebrand Factor (vWF). Equally important, miR-424 has been associated with hyper-coagulability whereas low levels of miR-103a have been observed in deep vein thrombosis, although precise mechanisms have not been defined for these miRNAs. Using a stepwise multiple regression analysis, exosomal miR-424 was an independent predictor of thromboembolic events ( i.e. pulmonary embolism and acute myocardial infarction ) in COVID-19 patients (Wald: 4.180; P&lt;0.05 ), whereas miR-103a independently regulated D-dimer levels ( P&lt;0.001 ). Conclusions: To our knowledge, this is the first study showing a significant contribution of exosomal non-coding RNAs in COVID19. Limitations of our study include the relatively small population and the fact that we did not determine the exact source of exosomes; nevertheless, we speculate that a main source could be represented by platelets and/or endothelial cells, which express these miRNAs in normal conditions.

D-Dimer As a Predictor of Thrombotic Events during Early Acute Lymphoblastic Leukemia Therapy

Background Patients with acute lymphoblastic leukemia (ALL) are at increased risk of thrombotic and or bleeding events during chemotherapy, especially when receiving L-Asparaginase (ASP). Previous studies have identified variables associated with increased thrombotic risk in ALL including age, body mass index (BMI), sex, platelet count, and ASP use (Orvain 2020); however, to date no ALL-based study has examined D-dimer, a marker of fibrinolysis that has been shown to predict thrombosis in acute myelogenous leukemia (AML) (Libourel 2016), in this context. We sought to examine the utility of D-dimer as a biomarker for risk of thrombosis or bleeding events during ALL treatment. Methods In this retrospective cohort study we identified 61 adult patients with newly diagnosed ALL from a single center between 2008 and 2020. Patient demographic details, treatment regimens, and biomarkers including D-dimer (ordered routinely at diagnosis as a serum assay in mcg/ml FEU) were ascertained. Patients were stratified according to D-dimer level using a cut-off of ≥4 mcg/ml (high) and &amp;lt;4 mcg/ml (low-moderate) based upon previous work examining D-dimer and thrombosis in AML (Libourel 2016). The disseminated intravascular coagulation (DIC) score according to the International Society on Thrombosis and Haemostasis (ISTH) was calculated at diagnosis. Major and clinically relevant non-major bleeding and first arterial or venous thrombotic event (confirmed by imaging) within 100 days of ALL diagnosis were recorded. The 100-day cumulative incidence of thrombosis was calculated for both D-dimer groups. Event rate was compared between D-dimer groups using chi-square analysis. Logistic regression was used to examine D-dimer as a continuous or categorical variable and compare events through 100 days. Six multivariate models, each including D-dimer and one of six previously identified thrombosis risk factors were performed. A receiver operating characteristic curve (ROC) was generated and area under the curve (AUC) calculated. Results Sixty-one patients with ALL were included; 52% were female and 48% male. Median age was 36 years (range 18-84). Patients were 18% Black, 26% Latinx, 52% White, and 3.3% Asian/Mideast Indian. Immunophenotypes included B-cell (82%), T-cell (8.2%), and mixed phenotype ALL (9.8%), with 24% of patients having Ph + or Ph-like status. ASP-based regimens were utilized in 67% of patients. The median D-dimer level was 2.1 mcg/ml (range: 0.26 to 20). The 100-day cumulative incidence of thrombosis was 53% (95% CI 26.4-73.8) in the high D-dimer group (N=17, 28%) and 14% (95% CI 5.5 - 25.5) in the low-moderate D-dimer group (N=44, 72%) (Figure 1). The rate of thrombosis was higher in the high D-dimer group, X2 (1, N=61) =10.2, p=.001. The odds of thrombosis within 100 days increased by 1.65 per every 3-unit increase in D-dimer (95% CI 1.2-2.27). The association between D-dimer and thrombosis remained after including additional confounders such as BMI, age, sex, ASP status, DIC score, and initial platelet level in covariate logistic regression models. ROC analysis demonstrated 60% sensitivity and 80% specificity for a D-dimer cutoff of 4 mcg/ml, with an AUC of 0.798 (95% CI 0.67-0.92). Clinically relevant bleeding occurred in 8 patients (13%) during the first 100 days after diagnosis and was not significantly associated with initial D-dimer level, BMI, age, sex, ASP status, DIC score, or initial platelet level. Conclusion High D-dimer (≥4 mcg/ml) at ALL diagnosis is associated with an increased rate of venous or arterial thrombosis within the first 100 days, with no increased rate of clinically relevant bleeding. D-dimer as a continuous variable appears to have good independent diagnostic discrimination for thrombosis. Prospective studies aiming to create ALL-specific thrombosis risk assessment models are warranted and should consider D-dimer level at diagnosis together with previously identified risk factors (Al-Ani 2020, Orvain 2020). Disclosures Leader: Bayer Healthcare: Other: personal fees ; Pfizer Pharmaceuticals Israel Ltd.: Consultancy, Honoraria, Other: personal fees .