Cross-linked Fibrin Degradation Products Research Articles

Changes in retinal circulation and choroidal thickness in patients with acute myeloid leukemia detected by optical coherence tomography angiography.

To investigate changes in retinal circulation and the choroid in patients with acute myeloid leukemia (AML) in the acute and remission stages, to analyze the correlation between retinal circulation and laboratory parameters, and to assess risk factors associated with leukemic retinopathy. Forty-eight patients (93 eyes) with AML were enrolled and divided into two groups according to fundus examination findings: the retinopathy and no retinopathy groups. Patients underwent eye measurements before treatment and after remission. Macular vessel density (VD), perfusion density (PD), foveal avascular zone (FAZ), and choroidal thickness (ChT) were measured using optical coherence tomography angiography. Patients with healthy eyes were recruited as control participants. Patients with leukemic retinopathy had higher measurements of white blood cells (WBCs), circulating blasts, fibrin degradation products, and cross-linked fibrin degradation products (D-dimer) and a lower hemoglobin (HB) count (p < 0.05). In the acute phase of the disease, the VD and PD were lower and the ChT was thicker in patients with AML than in controls (p < 0.05), irrespective of the presence of leukemic retinopathy; however, the patients were partially recovered in the remission stage. The VD was lower in patients with higher WBC (r = -0.217, p = 0.036), D-dimer (r = -0.279, p = 0.001), fasting blood glucose (FBG) (r = -0.298, p = 0.004) and triglyceride (r = -0.336, p = 0.001) levels. The FAZ area was negatively correlated with HB (r = -0.258, p = 0.012). Patients with AML appear to have subclinical retinal perfusion loss and choroidal thickening in the acute phase of the disease, but this is reversible. Injury to bone marrow function may cause a decrease in retinal perfusion. Leukemic retinopathy is associated with abnormal hematologic parameters and coagulopathy.

The prognostic value of admission D-dimer level in patients with cardiogenic shock after acute myocardial infarction.

Shock is associated with the activation of the coagulation and fibrinolytic system, and D-dimer is the degradation product of cross-linked fibrin. However, the prognostic value of D-dimer in patients with cardiogenic shock (CS) after acute myocardial infarction (AMI) remains unclear. We retrospectively analyzed the data of consecutive patients with CS complicating AMI. The primary endpoint was 30-day mortality and the secondary endpoint was the major adverse cardiovascular events (MACEs) including 30-day all-cause mortality, ventricular tachycardia/ventricular fibrillation, atrioventricular block, gastrointestinal hemorrhage, and non-fatal stroke. Restricted cubic spline (RCS) analyses were performed to assess the association between admission D-dimer and outcomes. A multivariable Cox regression model was performed to identify independent risk factors. The risk predictive potency with D-dimer added to the traditional risk scores was evaluated by C-statistics and the net reclassification index. Among 218 patients with CS complicating AMI, those who died during the 30-day follow-up presented with worse baseline characteristics and laboratory test results, including a higher level of D-dimer. According to the X-tile program result, the continuous plasma D-dimer level was divided into three gradients. The 30-day all-cause mortality in patients with low, medium, and high levels of D-dimer were 22.4, 53.3, and 86.2%, respectively (p < 0.001 for all). The 30-day incidence of MACEs was 46.3, 77.0, and 89.7%, respectively (p < 0.001). In the multivariable Cox regression model, the trilogy of D-dimer level was an independent risk predictor for 30-day mortality (median D-dimer cohort: HR 1.768, 95% CI 0.982-3.183, p = 0.057; high D-dimer cohort: HR 2.602, 95% CI 1.310-5.168, p = 0.006), a similar result was observed in secondary endpoint events (median D-dimer cohort: HR 2.012, 95% CI 1.329-3.044, p = 0.001; high D-dimer cohort: HR 2.543, 95% CI 1.452-4.453, p = 0.001). The RCS analyses suggested non-linear associations of D-dimer with 30-day mortality. The enrollment of D-dimer improved risk discrimination for all-cause death when combined with the traditional CardShock score (C-index: 0.741 vs. 0.756, p difference = 0.004) and the IABP-SHOCK II score (C-index: 0.732 vs. 0.754, p difference = 0.006), and the GRACE score (C-index: 0.679 vs. 0.715, p difference < 0.001). Similar results were acquired after logarithmic transformed D-dimer was included in the risk score. The improvements in reclassification which were calculated as additional net reclassification index were 7.5, 8.6, and 12.8%, respectively. Admission D-dimer level was independently associated with the short-term outcome in patients with CS complicating AMI and addition of D-dimer brought incremental risk prediction value to traditional risk prediction scores.

Abstract 460: Covid-19 And Acute Limb Ischemia: Arterial Thromboemboli Composition And Architecture

Objectives: The incidence of acute limb ischemia (ALI) has increased since the emergence of coronavirus disease 2019 (COVID-19) and has been linked to the serum level of cross-linked fibrin degradation products (D-dimer). The purpose of this study is to understand arterial thromboembolic architecture in patients with ALI and how this is altered by COVID-19 infection. Methods: Arterial thromboembolic specimens were prospectively collected at a single institution, stored in an IRB-approved tissue bank at -80°C for preservation of architecture. Liquid chromatography mass spectrometry (LC-MS/MS) was used to identify in-vivo Factor XIII (FXIII) generated cross-links, critical determinants of clot stability and strength. Protein composition of thromboemboli was compared between COVID and non-COVID patients. Results: Arterial thromboemboli were obtained from four patients. Patient #1 had COVID pneumonia and a D-dimer of 14,690 ng/mL FEU and developed ALI secondary to embolization of an aortic thrombus. Patients #2-4 did not have COVID and developed ALI secondary to synthetic graft thrombosis, septic embolization from endocarditis, and embolization during aortic arch replacement. COVID thromboemboli demonstrated a higher abundance of immune response proteins compared to non-COVID thromboemboli. Eighty-one cross-links were identified across the four specimens (Fig 1). A six-fold greater degree of Fibrinogen Alpha Chain (FibA-FibA) cross-linking was present in the COVID specimen (Mean: 295,100) compared to the mean of the three non-COVID specimens (Mean: 52,973) (Figure 2). Conclusions: A higher degree of cross-linking and increased levels of innate and adaptive immune response proteins appear to be features of arterial thromboemboli in COVID-induced ALI. This supports a virus-associated hypercoagulable state in COVID-19 patients with ALI.

Overall Survival Prediction of Advanced Cancer Patients by Selection of the Most Significant Baseline Serum Biomarker Combination.

Introduction: Consistent association between elevated baseline serum values and C-reactive protein (CRP), cross-linked fibrin degradation products (D-dimer), lactate dehydrogenase (LDH), decreased baseline serum albumin, absolute lymphocyte count to absolute monocyte count ratio (LMR), elevated absolute neutrophil count to absolute lymphocyte count ratio (NLR), elevated platelet count to absolute lymphocyte count ratio (PLR), and between some combinations of these biomarkers and the short overall survival of patients with malignant diseases has already been reported. These biomarkers are independent prognostic factors for cancer. Here, the most significant biomarker combination of these values was searched and studied in real-life advanced cancer patients of a single center. Methods: The authors retrospectively analyzed the association of the aforementioned biomarkers and their combination and OS of 75 consecutive cancer patients with locally advanced, recurrent, or metastatic diseases. Validated cut-off determination was used. Results: CRP, albumin, and PLR showed marked association with OS. Cut-off values for significant shorter OS were 30.65 mg/L (p < 0.001), 44.35 g/L (p < 0.001), and 168.20 (p < 0.001), respectively. Based on assessed biomarker cut-offs, four patient groups were created to determine whether biomarker values were out of range (ORV) compared to cut-off: 1) No ORV biomarkers (n = 24; OS = 26.07 months); 2) one ORV biomarker (n = 21; OS = 13.50 months); 3) two ORV biomarkers (n = 20; OS = 7.97 months), and 4) three ORV biomarkers (n = 10; OS = 3.91 months). Significant differences in OS were detected between the groups: For 1. vs. 2. hazard ratio (HR) = 3.0 (95% CI: 1.5–6.2), p = 0.003; for 1. vs. 3. HR = 4.1 (95% CI: 2.0–8.3), p < 0.001; and for 1. vs. 4. HR = 10.2 (95% CI: 4.2–24.6), p < 0.001. Conclusion: Based on our analysis, we can confirm that the complex monitoring of CRP, albumin, and PLR would provide a good estimation of OS. Large scale prospective studies are warranted to explore this and other useful combinations of prognostic biomarkers and their relationship to the well-established prognostic systems in real-life.

Plasma levels of leucocyte elastase-generated cross linked fibrin degradation products (E-XDP) are elevated in chronic venous disease.

Patients with chronic venous disease (CVD) have elevated levels of leucocyte elastase (LE) released from the activation of leucocytes. In acute deep venous thrombosis (DVT), LE can degrade fibrin from the thrombus resulting in cross-linked fibrin degradation products (E-XDP) being released into the bloodstream. In patients with CVD the levels and significance of circulating E-XDP are unknown. We aimed to investigate the association between plasma E-XDP concentration and severity of CVD. Levels of E-XDP were quantified with a specific enzyme-linked immunosorbent assay (ELISA) in plasma from 142 consecutively recruited CVD patients (mean age 64 years, (range 23–89), 81 were females and 61 males). Patients were also divided into three groups based on CVD severity using the C-class of the Clinical-Etiological-Anatomical-Pathophysiological (CEAP) classification, with C 0–1 class as the reference group, C 2–3 as the second group and C 4–6 as the third group with the most severely affected patients. We found significantly elevated levels of E-XDP in patients with C 4–6 compared with patients with C 0–1 (p = 0.007) and increased with increasing disease severity across the groups (p = 0.02). Significant independent association was observed between levels of E-XDP and the classes C 4–6 after adjustment for age and sex (p < 0.05), but the association was no longer significant after further adjustment for use of statins, use of anticoagulants and history of DVT (p = 0.247). This exploratory study shows that E-XDP levels are elevated in patients with CVD, encouraging further studies on the role of E-XDP in CVD.

Correlation of plasma D-dimer levels with breast carcinoma

Background: Breast cancer is the most commonly occurring cancer in women. There is a correlation between cancer and hyper coagulation. Carcinoma increases the level of cross-linked fibrin degradation product (plasma D-dimer), indicative of systemic activation of fibrinolysis, hemostasis and angiogenesis. This study attempted to correlate raised plasma D-dimer in breast cancer.Methods: A retrospective study was conducted in the department of general surgery in GCS hospital, Ahmedabad where in patients admitted and treated for breast cancer between July 2020 to June 2021 were selected. Plasma D-dimer levels were correlated with final histopathological examination of breast specimen.Results: Plasma D-dimer levels were increased with advancing stage of disease, lymph node involvement and lymphovascular invasion. There was no significant relationship with increase in tumour size and histopathological grade of tumour.Conclusions: Plasma D-dimer levels are elevated in breast cancer, especially with advanced stage. It is an important marker of clinical stage, lymphovascular invasion, lymph node involvement. However it does not correlate with tumour size and histological grade. So pre- operative plasma D-dimer level is a safe, cost effective and convenient method for prediction of advanced stage in breast cancer.

Clinical laboratory investigation of a patient with an extremely high D-dimer level: A case report

BACKGROUNDD-dimer, a soluble degradation product of cross-linked fibrin, is commonly used as an important marker for the diagnosis of disseminated intravascular coagulation and differential diagnosis of thrombosis. Herein, we present a geriatric case with an unusually elevated D-dimer level.CASE SUMMARYAn 82-year-old woman, admitted to the ward with a diagnosis of chronic heart failure, was noted to have a remarkably elevated D-dimer level, beyond the qualified range (> 100 mg/L), utilizing the Innovating D-dimer for Sysmex CS-5100 System™. However, no evidence, including clinical symptoms, radiographic evidence of thromboembolic disease, and parallel fibrinogen degradation product values, suggested that this patient was at high risk of thrombopenia. To confirm the discrepancy, a series of approaches including sample dilution, re-analysis via alternative methods, and sample treatment with blockage of specific heterophilic antibodies were performed. A remarkable disappearance of the elevated D-dimer values was observed in the samples after they were subjected to these approaches (4.49, 9.42, 9.06, and 12.58 mg/L, respectively). This confirmed the presence of heterophilic antibodies in this case. In addition, a reduction in cardiac output due to the presence of cardiac failure could also be responsible for the existence of a hypercoagulable state in this case.CONCLUSIONIn conclusion, the presence of heterophilic antibodies should be considered when an elevated D-dimer value is not in conformity with the clinical evidence, and a viral infection should be considered when interference by a heterophilic antibody exists.

D-Dimer and Fibrin Degradation Products Impair Platelet Signaling: Plasma D-Dimer Is a Predictor and Mediator of Platelet Dysfunction During Trauma.

Platelet dysfunction often accompanies trauma-induced coagulopathy. Because soluble fibrin impairs platelet glycoprotein VI (GPVI) signaling and platelets of trauma patients can display impaired calcium mobilization, we explored the role of fibrinolysis on platelet dysfunction during trauma. Convulxin-induced GPVI calcium mobilization was investigated in healthy platelet-rich plasma (PRP) pretreated with thrombin and tissue plasminogen activator (tPA). Blood samples from healthy participants (n = 7) and trauma patients (n = 22) were tested for platelet calcium mobilization, plasma D-dimer, platelet D-dimer binding (via flow cytometry), and platelet lumi-aggregometry. For healthy platelets, maximal platelet dysfunction was observed when cross-linked soluble fibrin (no tPA) or cross-linked fibrin degradation products (FDPs) were generated in suspension before convulxin stimulation. Lack of fibrin polymerization (inhibited by Gly-Pro-Arg-Pro [GPRP]) or lack of factor XIIIa cross-linking (T101-inhibited) restored GPVI signaling, whereas non-cross-linked FDPs only partially blocked signaling induced by convulxin. In addition, D-dimer added to healthy PRP impaired platelet aggregation and dense granule release induced by various agonists. Plasma D-dimer level was strongly correlated (R = 0.8236) with platelet dysfunction as measured by platelet calcium mobilization induced with various agonists. By 48 to 120 h after trauma, plasma D-dimer levels declined, and platelet function increased significantly but not to healthy levels. Trauma platelets displayed elevated D-dimer binding that was only partially reduced by αIIbβ3-inhibitor GR144053. After 60-minute incubation, washed healthy platelets resuspended in plasma from trauma patients captured approximately 10000 D-dimer equivalents per platelet. During trauma, D-dimer and FDPs inhibit platelets, potentially via GPVI and integrin αIIbβ3 engagement, contributing to a fibrinolysis-dependent platelet loss-of-function phenotype.

Clinical value of blood D-dimers in lower extremity deep venous thrombosis in patients with severe combined abdominal trauma

Aim. To establish sensitivity and specificity of deep vein thrombosis detection in patients with severe combined abdominal trauma by studying cross-linked fibrin degradation products (D-dimer) using erythrocyte agglutination SimpliRED® technology. Materials and methods . We analyzed the treatment results of 105 patients with severe combined abdominal trauma who underwent surgery inLvivThoraco-AbdominalTraumaCenter (Surgical Department No. 1), Traumatology and Neurosurgery Departments of the Lviv City Emergency Hospital in 2012–2017. Results. The sensitivity and specificity of lower extremity deep venous thrombosis detection in patients with severe combined abdominal trauma was established by studying D-dimers as well as their dynamics. Mandatory inclusion criteria for the study were: negative result of the D-dimer test upon admission, absence of instrumental and clinical signs of lower extremity deep venous thrombosis. The examination was performed prior to the operation or mini-invasive methods of diagnostics (laparoscopy) and on day 3 and 7 after. The high value of the method is explained by its maximum adaptation to the conditions of urgent surgery; it does not require specific inhibitors, does not depend on blood sampling technology or platelet count and can be performed in a few minutes. A positive result, which indicated the active fibrinolysis, was evaluated within 2 min by erythrocyte agglutination in a test cell and the latter absence in a control one. The D-dimer test was positive in 78 (74.3 %) patients in the study group. The peak of positive test results was observed on the 5th day after surgery. In all the injured with lower extremity deep venous thrombosis, a strong positive test result was revealed, which was manifested by erythrocyte agglutination at the 5–20 sec and the presence of D-dimers for a long time (an average of 19.3 ± 7.1 days). In the low-risk group of deep vein thrombosis and embolism by J. Caprini, the positive test was detected in 6 (5.7 %) patients, in the moderate and high-risk groups – in 28 (26.7 %) and 44 (41.9 %), respectively. Conclusions. The method of D-dimers detection in blood by SimpliRED ® technology showed a rather high sensitivity in patients with severe combined abdominal trauma of 82.3 %, but low specificity of 32.3 %. In the absence of prophylaxis, the incidence of deep vein thrombosis in patients with severe combined abdominal trauma was 25.7 %. The method of ultrasonic compression angioscanning of the lower extremity veins verified the proximal vein thrombosis predominance – 74.1 %. The risk of thrombus fragmentation and potential pulmonary thromboembolism was detected in 13.7 % of patients.

Predictive values of D-dimer for the long-term prognosis of acute ST-segment elevation infarction: A retrospective study in southwestern China.

D-dimer is a primary degradation product of cross-linked fibrin, and can be an effective diagnostic factor of venous thromboembolism. However, its prognostic role in patients with acute ST-segment elevation myocardial infarction (STEMI) remains controversial. This study aimed to investigate whether D-dimer has a predictive value for long-term prognosis in patients with STEMI.We retrospectively enrolled 872 STEMI patients treated with primary percutaneous coronary intervention. Patients were divided into quartiles according to their admission D-dimer increased multiple, with the highest quartile (G4) (n = 219) defined as increased multiple ≧1.33, and the lowest quartile (G1) (n = 215) as increased multiple ≦0.33.Compared with G1, higher in-hospital heart failure (40.2% vs 10.2%, P < .0001), malignant arrhythmia (14.2% vs 2.3%, P < .0001), and all-cause mortality (5.9% vs 0%, P < .0001) rates were observed in G4. After a follow-up period of 29 months, 84 patients had died. In the Cox multivariate analysis, a high admission D-dimer increased multiple (≧1.33) was found to be an independent predictor of all-cause mortality (hazards ratio: 2.53, 95% confidence interval: 1.02–6.26, P = .045).Thus, there was an association between a high D-dimer level and the increase in in-hospital major adverse cardiovascular events, such as heart failure, malignant arrhythmias, and death. High D-dimer level was also an independent predictor of long-term all-cause mortality.

Clinical application of a new latex photometric immunoassay reagent, LPIA-GENESIS D-dimer, and its performance in patient-derived plasma samples.

IntroductionWe previously reported an antibody MIF‐220 that recognizes a specific structure induced on the surface of thrombin‐activated E‐domain of one fibrin molecule bound with the D‐domains of other fibrinogen/fibrin molecules. Utilizing MIF‐220, we produced a test kit for cross‐linked fibrin degradation products (XDP), LPIA‐GENESIS D‐dimer (LG‐DD), and evaluated basic performance characteristics for clinical application. We then attempted to apply LG‐DD to see its eligibility in clinical plasma samples.MethodThe characteristic performances requested for clinical use were studied including limit of quantitation, within‐run imprecision, day‐to‐day imprecision, antigen excess, interference study, and method comparison with LPIAACE‐Ddimer (ACE‐DD) available on the market.ResultsThe performance characteristics were all satisfactory. Extraordinarily high concentrations of XDP are occasionally obtained by ACE‐DD in samples with collection problems, but not by LG‐DD, indicating that a certain XDP species present in the former was not measured by LG‐DD. Structural studies suggested that the “B‐b” set of polymerization sites must be involved as well in the maintenance of cross‐linked fibrin in vivo.ConclusionLG‐DD was able to measure a wide range of XDP, that is, 0.20‐35.0 μg FEU/mL that covers the levels of XDP in most of the clinical samples. LG‐DD was found to almost avoid false‐positive results noticed in samples as mentioned above, and this feature seems to be preferable to established kits for the measurement of XDP.

Elastase Fibrinolysis as a Marker of Presence, Size and Mechanical Stress of Abdominal Aortic Aneurysms and its Intraluminal Thrombi

Introduction - Most clinically relevant abdominal aortic aneurysms (AAA) contain an intraluminal thrombus (ILT) 1. The ILT entraps neutrophils, which secrete elastase with fibrinolytic activity, the process of which yields specific ‘neutrophil elastase-derived cross-linked fibrin degradation products’ (E-XDP) 2. Our hypothesis was that circulating E-XDP could reveal the presence, size and mechanical stress of AAAs and its ILTs. Methods - E-XDP was quantified by ELISA in plasma from 42 male patients with AAA and 42 male controls. The ILT volumes of the AAAs and any coexisting aneurysms could be measured in 32 patients. Finite element analysis was performed in the same 32 patients to estimate mechanical stress of the ILT. Local expression of E-XDP, neutrofil elastase and neutrophil marker CD66acd was studied by immunohistochemistry (IHC) in tissue from AAA and normal abdominal aorta. Wilcoxon rank sum test, receiver operating characteristic analysis, multivariate linear regression and Spearman’s rank were used to test univariate hypotheses, binary classification, correlations, and multivariate associations, respectively. Results - E-XDP levels were elevated in patients with AAA compared with controls (p = 6.9e-14), predicted AAA with 98% sensitivity and 88% specificity and correlated with the AAA diameter (r = 0.58, p = 5.3e-05). The association between AAA and increased E-XDP was independent of smoking, comorbidities and prescription drugs (p = 2.6e-06). Levels of E-XDP in patients with only a thin or macroscopically non-existent ILT were lower than those of patients with a large ILT, but remained significantly higher than in controls (p = 0.0026). Concentration of E-XDP correlated with volume of the ILTs in the AAAs (r = 0.75, p = 1.0e-06) and mean ILT stress (r = 0.42, p = 0.017), and was independently raised if coexisting aneurysms existed (p = 0.015). IHC revealed E-XDP expression in the ILT, which was spatially related to luminal neutrophil elastase and neutrophils. Conclusion - Circulating E-XDP is a novel marker of AAA and coexisting aneurysms, and correlates with AAA and ILT volume as well as with the mechanical stress of the ILT.

Plasma D-Dimer Levels Correlated With Advanced Breast Carcinoma in Female Patients: A Prospective Study at Baghdad Teaching Hospital

Abstract- Advanced breast cancer is a common disease among female gender in the world. There is a correlation between cancer and hypercoagulation. In a cancer state, there is an increase in the level of cross-linked fibrin degradation product (d-dimer) which indicates systemic activation of fibrinolysis and hemostasis. So, there is a relation between increase d-dimer value and advanced breast disease. To study the relation between preoperative plasma d-dimer level and tumor extension, choose the proper option of treatment, and to decrease morbidity and mortality in patients with breast carcinoma, a prospective study (cohort study) was done at Baghdad teaching hospital (department of surgery) from Jan 2014 to Jan 2016. Seventy patients were categorized into two equal groups, group one with breast carcinoma, and group two with benign breast tumor. Plasma d-dimer levels were compared for each group and in relation to (tumor size, stage, grade, lymphovascular invasion, and lymph nodes involvement). The d-dimer level was normal in group two (&lt;0.25 mg/l) and high in group one in other words, the d-dimer level was increasing in advanced breast carcinoma group with enlarged tumor size, higher stage and grade, lymphovascular invasion and lymph nodes’ involvement. Plasma d-dimer levels were a good prognostic factor in breast carcinoma especially in advanced breast carcinoma, and it could be considered a factor for clinical stage progression lymphovascular invasion, and metastasis.

Plasma d-dimer level correlated with advanced breast carcinoma in female patients.

BackgroundAdvanced breast cancer is a common disease among female in the world. There is a correlation between cancer and hyper coagulation. In a cancer state, there is an increase in the level of cross-linked fibrin degradation product (d-dimer)which indicates systemic activation of fibrinolysis and hemostasis. So, there is a relation between increase d-dimer value and advanced breast disease.ObjectiveTo confirm the relation between increase d-dimer levels and advanced breast carcinoma in female patients.Patients and methodsA prospective study (cohort study) done in Baghdad teaching hospital (department of surgery) from Jan 2014 to Jan 2016. Seventy patients were categorized intotwo equal groups, group 1 with breast carcinoma, group 2 with benign breast tumor. Plasma d-dimer levels compared for each group, and in relation to (tumor size, stage, grade, lympho-vascular invasion, and lymph nodes involvement).ResultsD-dimer level was normal in group two (<0.25) mg/l and high in group one in other words, d-dimer level was increasing in advanced breast carcinoma group with enlarge tumor size, high stage, grade, lympho-vascular invasion and lymph nodes involvement.ConclusionsPlasma d-dimer levels was good prognostic factor in breast carcinoma specially in advanced breast carcinoma and its considered factor clinical stage progression lympho-vascular invasion and metastasis.

Neutrophil Elastase-Derived Fibrin Degradation Products Indicate Presence of Abdominal Aortic Aneurysms and Correlate with Intraluminal Thrombus Volume.

The intraluminal thrombi (ILT) of abdominal aortic aneurysms (AAA) contain neutrophils, which can secrete elastase. We evaluated whether plasma neutrophil elastase-derived cross-linked fibrin degradation products (E-XDP) could reveal the presence, size and mechanical stress of AAAs and its ILTs. E-XDP and D-dimer were measured in plasma from 37 male patients with AAA and 42 male controls. The ILT volumes of the AAAs and any coexisting aneurysms could be measured in 29 patients and finite element analysis was performed to estimate mechanical stress of the ILT. E-XDP, neutrophil elastase and neutrophil marker CD66acd were evaluated in aortic tissue with immunohistochemistry (IHC). The association between ILT volume and E-XDP was validated in a separate cohort (n = 51). E-XDP levels were elevated in patients with AAA compared with controls (p = 5.8e-13), indicated AAA with 98% sensitivity, 86% specificity and increased with presence of coexisting aneurysms. The association between AAA and increased E-XDP was independent of smoking, comorbidities and medication. E-XDP correlated with volume of all ILTs (r = 0.76, p = 4.5e-06), mean ILT stress (r = 0.46, p = 0.013) and the volume of the AAA-associated ILT (r = 0.64, p = 0.00017). E-XDP correlated stronger with ILT volume compared with D-dimer (r = 0.76 vs. r = 0.64, p = 0.018). The correlation between E-XDP and ILT volume was validated in the separate cohort (r = 0.53, p = 7.6e-05). IHC revealed E-XDP expression in the ILT, spatially related to neutrophil elastase and neutrophils. E-XDP is a marker of the presence of AAA and coexisting aneurysms as well as the volume and mechanical stress of the ILT.

Value of D-dimer and alkaline phosphatase in the diagnosis of pleural effusion

IntroductionPleural effusion is a common clinical presentation in several diseases. Various parameters from pleural fluid have been studied to identify the cause of effusion. D-dimer is a degradation product of cross-linked fibrin and alkaline phosphatase (ALP) is one of the biochemical markers found in pleural effusion. ALP is a plasma membrane derived enzyme of uncertain physiologic function that hydrolyzes synthetic phosphate esters at pH 9. It is present in the serum in several forms, i.e., ALP-1 alpha 2, ALP-2 beta 1 and ALP-3 beta 2. AimThe present study was carried out to evaluate the value of alkaline phosphatase and D-dimer concentration in the pleural effusions and serum as a diagnostic tool. MethodsThis study was carried out on one hundred patients with pleural effusions of different aetiologies. 75 patients had exudative pleural effusions (35 patients had tuberculous effusion, 20 patients had malignant effusion, 10 had parapneumonic effusion, 5 had empyema and 5 patients had systemic lupus erythematosis) and 25 patients had transudative effusions (20 patients had hepatic and 5 patients had cardiac effusions). Serum and pleural effusion D-dimer (measured by ELISA), ALP, LDH and protein levels were measured. ResultsThere was a highly significant difference in the pleural fluid D-dimer and ALP levels between exudative and transudative effusions (P<0.001). Also, there was a highly significant difference in both the pleural fluid D-dimer and ALP levels between tuberculous and non tuberculous pleural effusions (P<0.001). There were no significant differences in the pleural levels of either the D-dimer or the ALP between malignant and non malignant pleural effusions (P>0.05). Lastly there was no significant difference (P>0.05) in the serum levels of either the ALP or the D-dimer between different types of effusions. ConclusionMeasurement of pleural fluid D-dimer and ALP levels aids in the differentiation between exudative and transudative pleural effusions. Also, both pleural fluid D Dimer and ALP are significantly higher in tuberculous pleural effusions.

Prognostic and predictive value of plasma D-dimer in advanced non-small cell lung cancer patients undergoing first-line chemotherapy

Previous studies have demonstrated that plasma D-dimer, a degradation product of cross-linked fibrin, correlated with tumor stage and prognosis in cancer patients. The aim of this study is to examine whether plasma D-dimer levels before and during chemotherapy predict tumor response and survival in advanced NSCLC patients undergoing first line chemotherapy. Plasma D-dimer levels before (B0), and after one (B1) and two (B2) cycles of chemotherapy in 82 patients with advanced NSCLC were measured and correlated with treatment response, clinical features, progression-free survival (PFS) and overall survival. A significant correlation was identified between changes in D-dimer levels before and after two chemotherapy cycles and treatment response. In addition, there were significant correlations between D-dimer positivity at B0, B1 and B2 time points and tumor stage, number of metastatic sites and treatment response. Patients with positivity of D-dimer at B0, B1 and B2 had significantly shorter PFS compared with those with negativity. Notably, positivity of D-dimer at B1 and B2 time points was an independent predictive factor for unfavorable PFS. The positivity of D-dimer before and during chemotherapy is a predictor of treatment response and worse PFS in patients with advanced NSCLC. D-dimer levels provide prognostic information in addition to that of imaging studies.

English

Traumatic Brain Injury (TBI) is damage in the brain caused by a traumatically injuring external force. To observe its severity, the Glasgow Coma Scale (GCS) and Computed Tomography (CT) scan are used. In addition, D-dimer as an end product of fibrinolytic activity is proposed as the predictor of TBI outcome. The increase of D-dimer value is correlated with severity. CT-scan is too expensive and requires patients’ mobility that can cause worse incidents. The aim of this study was to correlate between D-dimer and GCS in patients with traumatic brain injury. The cross sectional observational analytic design was carried out in the study. The TBI patients with 24 hours onset admitted to Emergency Room Dr. Sardjito Hospital Yogyakarta will be included with inclusion and exclusion criteria consecutively. Glasgow coma scale was measured and plasma D-Dimer was examined using Nycocard with immunofiltration method. Correlation between plasma D-Dimer and Glasgow Coma Scale was tested using Pearson Correlation when the population distribution was normal and Spearman when it was not normally distributed. There was a strong negative correlation between D-dimer and Glasgow Coma Scale (r=-0.622; p<0.001) and Prothrombin Time with D-dimer value (r=0527; p<0.001). Moreover, it was found that haemoglobin had a correlation with D-dimer (r=-0.517; p=0.001). Haemoglobin and PT had a correlation with Glasgow Coma Scale (r=0.419 vs -0.591; p<0.001) and neutrophil had poor correlation with Glasgow Coma Scale (r=- 0.336; p=0.034). In conclusion, there was a strong negative correlation between degradation product of cross-linked fibrin (D-dimer) and Glasgow Coma Scale in patients with traumatic brain injury. Keywords : D-Dimer - Glasgow Coma Scale - Traumatic Brain Injury - CT scan - correlation /* Style Definitions */ table.MsoNormalTable {mso-style-name:Table Normal; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:Calibri,sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:Times New Roman; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Times New Roman; mso-bidi-theme-font:minor-bidi;}

Preoperative plasma D‐dimer predicts 1‐year survival in colorectal cancer patients with absence of venous thromboembolism (VTE): a prospective clinical cohort study

Fibrin formation is required for tumor angiogenesis, metastasis and invasion. Cancer discovered at the same time as or shortly after venous thromboembolism (VTE) tends to be advanced, and the prognosis poor. Previous studies have demonstrated that plasma D-dimer - a degradation product of cross-linked fibrin - correlates with tumor stage and prognosis in patients with colorectal cancer. However, it remains unclear whether D-dimer is of prognostic significance in colorectal cancer patients with absence of VTE. To examine whether the preoperative plasma D-dimer level predicts 1-year survival in pre- and postoperative VTE-negative colorectal cancer patients admitted for surgery. We measured preoperative D-dimer levels in 157 patients, and computed Kaplan-Meier survival curves according to the levels of D-dimer. Cox proportional-hazard regression analysis was used to compute hazard ratio as a measure of 1-year mortality rate ratio, controlling for potential confounding factors. The Aalborg Hospital's standard cut-off level of 0.3 mg L(-1) was used to distinguish negative and positive D-dimer results. The overall 1-year survival rate was 87.3% (95% confidence interval (CI), 81.0-91.6%), with 78.1% survival (95% CI, 65.9-86.4%) in the positive D-dimer group compared with 93.6% survival (95% CI, 86.2-97.1%) in the negative D-dimer group. The adjusted hazard ratio of death in the positive D-dimer group compared with the negative D-dimer group was 3.6 (95% CI, 1.3-9.9). A positive preoperative D-dimer is associated with a poor prognosis in colorectal cancer patients with absence of VTE.

Venous thromboembolism and coagulation activity in patients with immune thrombocytopenia treated with thrombopoietin receptor agonists

Venous thromboembolism and coagulation activity in patients with immune thrombocytopenia treated with thrombopoietin receptor agonists