Plasma D-dimer Concentration Research Articles

Predicting Progressive Hemorrhagic Injury Following Traumatic Brain Injury by the Evaluation of D-Dimer/Fibrinogen Ratio

Abstract Background Prognosis of traumatic brain injury (TBI) significantly depends on the incidence of progressive hemorrhagic injury (PHI). The present study was conducted to assess whether D-dimer/fibrinogen ratio can predict PHI among the patients with TBI. Materials and Methods A total of 150 patients were included in this retrospective study; among them 72 had PHI and 78 did not have PHI. Demographic, clinical, radiological, and laboratory parameters including plasma D-dimer and plasma fibrinogen levels and subsequently D-dimer/fibrinogen ratio were evaluated. Independent t-test, Mann–Whitney U test, chi-square test, Fisher's exact test, and multivariate logistic regression were used for statistical analysis. Results Age, injury time, first computed tomography time, Glasgow Coma Scale scores, unreactive pupils, abnormal cisterns, midline shift above 5 mm, skull base fracture, epidural hematoma, subdural hematoma, intraventricular hemorrhage, cerebral hematoma, brain contusion, plasma D-dimer concentration, plasma fibrinogen concentration, and D-dimer/fibrinogen ratio vary significantly between PHI and non-PHI groups (p < 0.05). Multivariate logistic regression showed that the Glasgow Coma Scale score (odds ratio [OR], 0.531; 95% confidence interval [CI], 0.436–0.648; p = 0.004) and D-dimer/fibrinogen ratio (OR, 3.784; 95% CI, 2.086–6.867; p = 0.027) were the two independent predictors for PHI. Conclusion D-dimer/fibrinogen ratio is a useful parameter in predicting the incidence of PHI among the patients with TBI.

Clinical value of measuring plasma D-dimer levels in patients with esophageal cancer

BackgroundEsophageal cancer represents a significant public health concern; however, reliable diagnostic and prognostic markers have not been established. This study aimed to investigate the clinical value of plasma D-dimer levels in patients with esophageal cancer.MethodsOverall, 120 patients with esophageal cancer who underwent radical surgical resection at our department between January 2019 and 2020 were included (esophageal cancer group). Plasma D-dimer levels were measured preoperatively and on postoperative days 1 and 14. Additionally, 60 healthy participants (control group) with measured plasma D-dimer levels were included. The preoperative D-dimer levels and positive D-dimer test rates were compared between the groups. The 3-year survival rate in patients with esophageal cancer was calculated using the Kaplan–Meier method.ResultsPreoperative D-dimer concentration in the esophageal cancer group was (0.65 ± 0.859 µg/mL) significantly higher than that in the control group (0.32 ± 0.369 µg/mL). The positivity rate in the esophageal cancer group (35.0%, 42/120) was significantly higher than that in the control group (15%, 9/60). D-dimer concentrations were significantly higher 1 day postoperatively than preoperatively. Conversely, D-dimer concentrations were significantly lower 14 days postoperatively than preoperatively. Patients in the esophageal cancer group with plasma D-dimer concentrations ≤ 0.5 µg/mL had significantly higher 3-year survival rates than those with higher concentrations. In the logistic multivariate analysis, tumor pathological stage and preoperative plasma D-dimer levels were independent prognostic factors of 3-year survival rates in patients with esophageal cancer.ConclusionPlasma D-dimer concentrations are clinically valuable in esophageal cancer diagnosis, postoperative recurrence monitoring, and prognosis prediction.

A new surface plasmon resonance-based immunoassay for rapid and sensitive quantification of D-dimer in human plasma for thrombus screening

D-dimer is a protein fragment generated during the fibrin breakdown by plasmin, and it serves as a mature biomarker for diagnosing thrombotic disorders. A novel immunoassay method based on surface plasmon resonance (SPR) has been developed, validated, and successfully applied for the quantification of D-dimer in human plasma with high sensitivity and rapidity. In this methodological study, we investigated the activity and stability of the SPR biosensor, sample pre-processing, washing conditions, intra-day and inter-day precision and accuracy and detection parameters, including a limit of detection of 8.3 ng/mL, a detection range spanning from 31.25 to 4000 ng/mL, and a detection time of 20 min. We compared D-dimer plasma concentration determination results using SPR with a classical latex-enhanced immunoturbidimetric immunoassay in 29 healthy individuals and thrombotic patients, and both methods exhibited consistency. Furthermore, we propose a hypothesis about the relationship between the concentration of D-dimer and its molecular weight. With an increase in the D-dimer concentration in plasma, the D-dimer approaches its simplest form (190 kDa).

Rivaroxaban versus enoxaparin plus clopidogrel therapy for hypertrophic cardiomyopathy-associated thromboembolism in cats

Background and Aim: Cardiogenic embolism (CE) is a common complication of feline hypertrophic cardiomyopathy (HCM), leading to severe clinical symptoms. This study compared the effects of rivaroxaban and enoxaparin combined with clopidogrel on cats. Materials and Methods: This was a single-center, prospective, randomized controlled trial. In this study, rivaroxaban or enoxaparin plus clopidogrel was prescribed to 23 cats for at least one of the following events: Abnormal movement of the anterior mitral leaflet during systole, enlargement of the left atrium, spontaneous echocardiographic contrast, or presence of arterial thromboembolism. Oral rivaroxaban (2.5 mg, q24 h) was prescribed to six cats. Subcutaneous injections of enoxaparin (1 mg/kg, q24 h) plus oral clopidogrel (3 mg/kg, PO q24 h) for 60 days were administered to 17 cats. Renal insufficiency and bleeding complications were observed. Plasma concentrations of D-dimer, prothrombin time (PT), partial thromboplastin time, and international normalized ratio (INR) were evaluated. We analyzed the relationship between echocardiography parameters and the effects of coagulation. Blood samples were collected from all cats at baseline and at 1 and 2 months post-treatment. Results: Rivaroxaban alone and in combination with enoxaparin and clopidogrel significantly affected PT and INR. In cats treated with 2.5 mg/kg rivaroxaban for 60 days, no bleeding or recurrence of thrombus formation was observed. These data support the use of rivaroxaban for the treatment of HCM-associated thromboembolism in cats. Conclusion: Treatment of HCM-associated thromboembolism with rivaroxaban alone demonstrated clinical effectiveness with no clinical complications in cats. Keywords: cardiomyopathy, D-dimer, echocardiography, prothrombin time.

High Risk of Stroke in Patients With Worsening Heart Failure, Reduced Ejection Fraction, Coronary Heart Disease and Sinus Rhythm: Risk Prediction Score Analysis From the COMMANDER-HF Trial

BackgroundPatients with heart failure with reduced ejection fraction (HFrEF) and sinus rhythm have a heightened risk of stroke. Whether anticoagulation benefits these patients is uncertain. In this post hoc analysis of the A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure (COMMANDER-HF) trial we evaluated how a previously validated risk model consisting of 3 variables (history of prior stroke, insulin-treated diabetes, and N-terminal pro-B-type natriuretic peptide level) would perform, compared with plasma d-dimer, for stroke prediction and estimation of the benefit of low-dose rivaroxaban. Methods and ResultsStroke risk and treatment effect were computed across risk score and plasma d-dimer tertiles. Risk score was available in 58% of the COMMANDER-HF population (n = 2928). Over a median follow-up of 512 days (range 342–747 days), 60 patients experienced a stroke (14.6 per 1000 patient-years). The risk model did not identify patients at higher risk of stroke and showed a low overall prognostic performance (C-index = 0.53). The effect of rivaroxaban on stroke was homogeneous across risk score tertiles (P-interaction = .67). Among patients in whom the risk score was estimated, d-dimer was available in 2343 (80%). d-dimer had an acceptable discrimination performance for stroke prediction (C-index = 0.66) and higher plasma d-dimer concentrations were associated with higher rates of stroke (ie, tertile 3 vs tertile 1, hazard ratio 3.65, 95% confidence interval 1.59–8.39, P = .002). Treatment with low-dose rivaroxaban reduced the incidence of stroke in patients at highest risk by d-dimer levels (ie, >515 ng/mL, hazard ratio 0.42, 95% confidence interval 0.18–0.95, P-interaction = .074), without any safety concerns. ConclusionsIn our analysis, plasma d-dimer concentrations performed better than a previously described 3-variable risk score for stroke prediction in patients with heart failure with reduced ejection fraction, a recent clinical worsening and sinus rhythm as enrolled in the COMMANDER-HF trial. In these patients, a raised plasma d-dimer concentration identified patients who might benefit most from rivaroxaban.

Fast screening using attenuated total reflectance- fourier transform infrared (ATR-FTIR) spectroscopy of patients based on D-dimer threshold value

Attenuated Total Reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy is an emerging technology in the medical field. Blood D-dimer was initially studied as a marker of the activation of coagulation and fibrinolysis. It is mainly used as a potential diagnosis screening test for pulmonary embolism or deep vein thrombosis but was recently associated with COVID-19 severity. This study aimed to evaluate the use of ATR-FTIR spectroscopy with machine learning to classify plasma D-dimer concentrations. The plasma ATR-FTIR spectra from 100 patients were studied through principal component analysis (PCA) and two supervised approaches: genetic algorithm with linear discriminant analysis (GA-LDA) and partial least squares with linear discriminant (PLS-DA). The spectra were truncated to the fingerprint region (1800–1000 cm−1). The GA-LDA method effectively classified patients according to D-dimer cutoff (≤0.5 μg/mL and >0.5 μg/mL) with 87.5 % specificity and 100 % sensitivity on the training set, and 85.7 % specificity, and 95.6 % sensitivity on the test set. Thus, we demonstrate that ATR-FTIR spectroscopy might be an important additional tool for classifying patients according to D-dimer values. ATR-FTIR spectral analyses associated with clinical evidence can contribute to a faster and more accurate medical diagnosis, reduce patient morbidity, and save resources and demand for professionals.

D-dimer, C-reactive protein and matrix metalloproteinase 9 for prediction of type A aortic dissection patient survival.

Acute type A aortic dissection (ATAAD) is a life-threatening condition requiring prompt diagnosis and treatment. Surgery is an effective treatment for ATAAD, but the in-hospital mortality rate in the 30day perioperative period is still as high as 9-30%. It is critical to identify biological factors for preoperative assessment of post-operative survival in patients with ATAAD. This is a retrospective study, investigating the association of combined measurements of d-dimer, C-reactive protein (CRP), and matrix metalloproteinase 9 (MMP9) for 1year of survival in patients with ATAAD. Data from 247 patients who underwent surgery were analysed, including 89 patients who did not survive and 158 patients who survived within 1year after surgery. Pearson's correlation analysis was carried out to determine the correlations between CRP in whole blood, d-dimer in plasma, and CRP in whole blood. Receiver operating characteristic (ROC) analysis was used to analyse the value of preoperative whole blood CRP, plasma d-dimer, and serum MMP9 concentration and the combined detection model in predicting death of patients with ATAAD. Deceased patients with ATAAD exhibited higher age, hypertension prevalence, systolic blood pressure, white blood cell count, whole blood CRP, plasma d-dimer, and serum MMP9 levels compared with survivors. Preoperative CRP, d-dimer, and MMP9 levels were significantly higher in patients with ATAAD compared with healthy controls. Positive correlations were observed between CRP and d-dimer, CRP and MMP9, and d-dimer and MMP9 in patients with ATAAD. ROC analysis showed that the combined detection model of CRP, d-dimer, and MMP9 had the highest predictive value for 1year of survival (area under the curve=0.88). Combined measurement of CRP, d-dimer, and MMP9 is associated with 1year of survival in patients with ATAAD.

Risk factors for lower extremity deep vein thrombosis in acute stroke patients following endovascular thrombectomy: a retrospective cohort study.

Deep vein thrombosis (DVT) in lower extremities as a common complication of acute ischemic stroke (AIS) has long been studied. However, as the therapeutic options for AIS continue to advance, the pathogenic mechanisms behind DVT may change. Endovascular thrombectomy (EVT) has replaced intravenous thrombolysis and become the preferred treatment for AIS patients with large vessel occlusions. Therefore, it is important to update our understanding of DVT and its management. This study aimed to determine the prevalence and risk factors of DVT in AIS patients following EVT. In this retrospective study, 245 AIS patients who had received EVT were recruited between January 2020 and December 2021. Within 10 days (median 4 days) of thrombectomy, DVT was diagnosed by ultrasonography. Demographic characteristics, clinical findings, and therapeutic procedures were compared between patients with and without DVT using univariate analysis. Cutoff points were defined for EVT time and plasma D-dimer concentration. Multivariable logistic regression was then used to determine the independent risk factors for DVT and evaluate their predictive power. The prevalence of DVT in AIS patients after EVT was 27.3%. Multifactorial logistic regression analysis showed that age (OR 1.036, 95% CI 1.001-1.073; P = 0.045), female sex (OR 3.015, 95% CI 1.446-6.289; P = 0.003), lower limb muscle strength less than grade three (OR 7.015, 95% CI 1.887-26.080; P = 0.004), longer EVT time (OR 1.012, 95% CI 1.004-1.020; P = 0.003), and higher D-dimer levels (OR 1.350, 95% CI 1.150-1.585; P < 0.001) were independently associated with higher DVT risk in AIS patients following EVT. The cutoff points for operative time of EVT and plasma D-dimer were 65.5 min and 1.62 mg/L, respectively, above which the risk for DVT was dramatically increased with OR > 4 in AIS patients. AIS patients are at increased risk of developing DVT following EVT particularly if they have undergone prolonged thrombectomy procedures and exhibit high plasma levels of D-dimers. However, the results of our study need to be validated by a multicenter prospective study with a larger population of stroke patients.

Association between fatty liver index and blood coagulation markers: a population-based study

BackgroundPopulation-based studies investigating the association between blood coagulation markers and non-alcoholic fatty liver disease (NAFLD) are rare. Thus, we aimed to investigate the relationship between the Fatty Liver Index (FLI) as a measure of hepatic steatosis and plasma concentrations of antithrombin III, D-dimer, fibrinogen D, protein C, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value and international thromboplastin time (INR) in the general population.MethodsAfter the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men, aged 54–74 years) of the population-based KORA Fit study with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the associations between FLI and hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the history of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol levels, and diabetes status. In addition, analyses were stratified by diabetes status.ResultsIn the multivariable models (with or without health conditions), significantly positive associations with FLI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein C, protein S, and quick value, while INR and antithrombin III were inversely associated. These associations were weaker in pre-diabetic subjects and largely disappeared in diabetic patients.ConclusionIn this population-based study, an increased FLI is clearly related to changes in the blood coagulation system, possibly increasing the risk of thrombotic events. Due to a generally more pro-coagulative profile of hemostatic factors, such an association is not visible in diabetic subjects.

Construction of a nomogram risk prediction model for PICC-related venous thrombosis and its application

ObjectiveTo explore the risk factors of the peripherally inserted central catheter (PICC)-related venous thrombosis and correspondingly construct a nomogram risk prediction model. MethodsThe clinical data of 401 patients receiving PICC catheterization in our hospital from June 2019 to June 2022 were retrospectively analyzed. The independent influencing factors for venous thrombosis were predicted using logistic regression analysis, and significant indicators were screened to construct a nomogram for predicting PICC-related venous thrombosis. The difference in predictive efficacy between simple clinical data and nomogram was analyzed using a receiver operating characteristic (ROC) curve, and the nomogram was internally validated. ResultsSingle-factor analysis showed that catheter tip position, plasma D-dimer concentration, venous compression, malignant tumor, diabetes, history of thrombosis, history of chemotherapy, and history of PICC/CVC catheterization were correlated with PICC-related venous thrombosis. Further multi-factor analysis revealed that catheter tip position, plasma D-dimer elevation, venous compression, history of thrombosis and history of PICC/CVC catheterization were the risk factors for PICC-related venous thrombosis. Based on binary logistic regression analysis, a nomogram prediction model for PICC-related venous thrombosis was constructed. The area under the curve (AUC) was 0.876 (95%CI: 0.818–0.925), with a statistically significant difference (P < 0.01). ConclusionThe independent risk factors for PICC-related venous thrombosis are screened out, including catheter tip position, plasma D-dimer elevation, venous compression, history of thrombosis and history of PICC/CVC catheterization, and a nomogram prediction model with good effect is constructed to predict the risk of PICC-related venous thrombosis.

Administration of Warfarin Inhibits the Development of Cerulein-Induced Edematous Acute Pancreatitis in Rats.

Acute pancreatitis (AP) is a severe disease with high morbidity and mortality in which inflammation and coagulation play crucial roles. The development of inflammation leads to vascular injury, endothelium and leukocytes stimulation, and an increased level of tissue factor, which results in the activation of the coagulation process. For this reason, anticoagulants may be considered as a therapeutic option in AP. Previous studies have shown that pretreatment with heparin, low-molecular-weight heparin (LMWH), or acenocoumarol inhibits the development of AP. The aim of the present study was to check if pretreatment with warfarin affects the development of edematous pancreatitis evoked by cerulein. Warfarin (90, 180, or 270 µg/kg/dose) or saline were administered intragastrically once a day for 7 days consecutively before the induction of AP. AP was evoked by the intraperitoneal administration of cerulein. The pre-administration of warfarin at doses of 90 or 180 µg/kg/dose reduced the histological signs of pancreatic damage in animals with the induction of AP. Additionally, other parameters of AP, such as an increase in the serum activity of lipase and amylase, the plasma concentration of D-dimer, and interleukin-1β, were decreased. In addition, pretreatment with warfarin administered at doses of 90 or 180 µg/kg/dose reversed the limitation of pancreatic blood flow evoked by AP development. Warfarin administered at a dose of 270 µg/kg/dose did not exhibit a preventive effect in cerulein-induced AP. Conclusion: Pretreatment with low doses of warfarin inhibits the development of AP evoked by the intraperitoneal administration of cerulein.

Relationship between D-dimers and dead-space on disease severity and mortality in COVID-19 acute respiratory distress syndrome: A retrospective observational cohort study

BackgroundDespite its diagnostic and prognostic importance, physiologic dead space fraction is not included in the current ARDS definition or severity classification. ARDS caused by COVID-19 (C-ARDS) is characterized by increased physiologic dead space fraction and hypoxemia. Our aim was to investigate the relationship between dead space indices, markers of inflammation, immunothrombosis, severity and intensive care unit (ICU) mortality. ResultsRetrospective data including demographics, gas exchange, ventilatory parameters, and respiratory mechanics in the first 24 h of invasive ventilation. Plasma concentrations of D-dimers and ferritin were not significantly different across C-ARDS severity categories. Weak relationships were found between D-dimers and VR (r = 0.07, p = 0.13), PETCO2/PaCO2 (r = −0.1, p = 0.02), or estimated dead space fraction (r = 0.019, p = 0.68). Age, PaO2/FiO2, pH, PETCO2/PaCO2 and ferritin, were independently associated with ICU mortality. We found no association between D-dimers or ferritin and any dead-space indices adjusting for PaO2/FiO2, days of ventilation, tidal volume, and respiratory system compliance. ConclusionsWe report no association between dead space and inflammatory markers in mechanically ventilated patients with C-ARDS. Our results support theories suggesting that multiple mechanisms, in addition to immunothrombosis, play a role in the pathophysiology of respiratory failure and degree of dead space in C-ARDS.

Plasma Concentration of d-Dimer for Venous Thromboembolism Detection in Immobilized Trauma Patients

Plasma Concentration of d-Dimer for Venous Thromboembolism Detection in Immobilized Trauma Patients

Body Mass Index and Waist Circumference as Determinants of Hemostatic Factors in Participants of a Population-Based Study.

Background: In contrast to studies in patients, an association between obesity and blood coagulation factors has not been established in the population. If confirmed it could become a target for primary prevention. Objective: To investigate the relationship between Body Mass Index (BMI) and waist circumference (WC) with plasma concentrations of antithrombin III, D-dimers, fibrinogen D, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value, and international normalized ratio (INR) in the general population. Materials and Methods: Participants of the Cooperative Health Research in the Region of Augsburg (KORA) S4 study who took part in the KORA Fit follow-up (2018-2019, aged 54-74 years) examination were eligible. Citrate plasma samples were collected in fasted participants. After the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men) with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the association between BMI or WC with hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the prevalence of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol, and serum triglycerides. Results: In the multivariable models (with or without health conditions), significant positive associations with BMI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein S, and quick value, while INR and antithrombin III were inversely associated. Similar to BMI, WC was significantly associated with all hemostatic factors, except for aPTT. Conclusion: In this population-based study, both increasing BMI and WC affect the blood coagulation system. Thus, modification of a prothrombotic coagulation profile emerged as a potential target for primary prevention in obese subjects.

Diagnosis and Stratification of COVID-19 Infections Using Differential Plasma Levels of D-Dimer: A Two-Center Study from Saudi Arabia

Background: D-dimer, generated upon the degradation of fibrin, is extensively used to detect thrombosis in various diseases. It is also explored as a marker for thrombosis in cases with COVID-19 disease. Few studies have confirmed its utility as a marker for assessing disease severity. Objectives: The current research was undertaken to determine the role of D-dimer in patients with COVID-19 and to investigate any association with the progression and severity of the disease in the Saudi population. Methods: Clinical indices in confirmed COVID-19 patients were collected from tertiary care hospitals in Aljouf and Qassim regions. The plasma D-dimer levels were quantified directly in the samples collected from COVID-19 patients (n = 148) using an immunofluorescence assay, and the data were presented in Fibrinogen Equivalent Units (mg/L). The collected data of D-dimer were analyzed based on COVID-19 severity, age, and the gender of patients. Results: The findings show that the plasma D-dimer concentrations were significantly (p = 0.0027) elevated in COVID-19 cases (n = 148), compared to in the normal healthy uninfected controls (n = 309). Moreover, the D-dimer levels were analyzed according to the severity of the disease in the patients. The data revealed that D-dimer concentrations were significantly increased in patients with mild infection to moderate disease, and the levels were the highest in patients with severe COVID-19 disease (p &lt; 0.05). Our analysis demonstrates that the D-dimer levels have no association with the age or gender of COVID-19 patients (p &gt; 0.05) in the study population. Conclusions: D-dimer can serve as a biomarker not only for the detection of COVID-19 infection, but also for determining the severity of infection of COVID-19 disease.

Evaluation of long-term sequelae by cardiopulmonary exercise testing 12 months after hospitalization for severe COVID-19

BackgroundCardiopulmonary exercise testing (CPET) is an important clinical tool that provides a global assessment of the respiratory, circulatory and metabolic responses to exercise which are not adequately reflected through the measurement of individual organ system function at rest. In the context of critical COVID-19, CPET is an ideal approach for assessing long term sequelae.MethodsIn this prospective single-center study, we performed CPET 12 months after symptom onset in 60 patients that had required intensive care unit treatment for a severe COVID-19 infection. Lung function at rest and chest computed tomography (CT) scan were also performed.ResultsTwelve months after severe COVID-19 pneumonia, dyspnea was the most frequently reported symptom although only a minority of patients had impaired respiratory function at rest. Mild ground-glass opacities, reticulations and bronchiectasis were the most common CT scan abnormalities. The majority of the patients (80%) had a peak O2 uptake (V′O2) considered within normal limits (median peak predicted O2 uptake (V′O2) of 98% [87.2–106.3]). Length of ICU stay remained an independent predictor of V′O2. More than half of the patients with a normal peak predicted V′O2 showed ventilatory inefficiency during exercise with an abnormal increase of physiological dead space ventilation (VD/Vt) (median VD/VT of 0.27 [0.21–0.32] at anaerobic threshold (AT) and 0.29 [0.25–0.34] at peak) and a widened median peak alveolar-arterial gradient for O2 (35.2 mmHg [31.2–44.8]. Peak PetCO2 was significantly lower in subjects with an abnormal increase of VD/Vt (p = 0.001). Impairments were more pronounced in patients with dyspnea. Peak VD/Vt values were positively correlated with peak D-Dimer plasma concentrations from blood samples collected during ICU stay (r2 = 0.12; p = 0.02) and to predicted diffusion capacity of the lung for carbon monoxide (DLCO) (r2 = − 0.15; p = 0.01).ConclusionsTwelve months after severe COVID-19 pneumonia, most of the patients had a peak V′O2 considered within normal limits but showed ventilatory inefficiency during exercise with increased dead space ventilation that was more pronounced in patients with persistent dyspnea.Trial registration: NCT04519320 (19/08/2020).

No changes in hemostasis after COVID-19–heterologous vaccination schedule: A subanalysis of the phase 2 CombiVacS study

BackgroundSeveral cases of unusual thrombotic events and thrombocytopenia were described after vaccination with recombinant adenoviral vectors encoding the spike protein antigen of SARS-CoV-2. ObjectivesThe objective of this study was to elucidate the impact of a COVID-19 heterologous vaccination schedule, including priming with adenovirus vaccine, on hemostasis profiles. MethodsThe present study is a subanalysis of the CombiVacS clinical trial initiated in April 2021 that included adult participants previously vaccinated with a single dose of ChAdOx1-S. Between 8 and 12 weeks after vaccination, they were randomly assigned (2:1) to receive either BNT162b2 vaccine (intervention group, n = 99) or continue observation (control group, n = 50). Samples drawn before and 28 days after a vaccination with BNT162b2 were analyzed for platelet count and markers of hemostasis (D-dimer, anti-PF4 antibodies, cfDNA, PAI-1, thrombin generation, and serum capacity to activate platelets). ResultsPlatelet count from all participants after receiving BNT162b2 was within the normal range. Anti-PF4 antibodies were present in 26% and 18% of the subjects from the control and intervention groups, respectively, at day 28. In most cases, the levels of anti-PF4 antibodies were high before receiving BNT162b2. Serum from these participants did not activate platelets from healthy controls. There were no differences between the groups in PAI-1 and cfDNA plasma levels. According to the D-dimer plasma concentration, the thrombin generation test showed that none of the participants had a procoagulant profile. ConclusionOur data suggest that the heterologous vaccination against COVID-19 with ChAdOx1-S and a second dose with BNT162b2 might be safe in terms of haemostasis.

Elevated Plasma D-Dimer Concentrations in Adults after an Outpatient-Treated COVID-19 Infection.

Elevated D-dimer plasma concentrations are common in hospitalized COVID-19 patients and are often associated with a worse prognosis, but it is not yet clear whether this also applies to outpatient cases. The present cross-sectional study evaluated D-dimer levels and their association with clinical parameters and inflammation biomarkers after a COVID-19 disease in individuals treated as outpatients. The study included 411 individuals (43.3% men) with an average age of 46.8 years (SD 15.2). Study participants who had acute COVID-19 disease at a median of 235 days (120; 323) ago were examined at the University Hospital Augsburg, Southern Germany, between 11/2020 and 05/2021. Plasma D-dimers were measured by a particle-enhanced immunoturbidimetric assay. Sixty-one subjects (15%) showed increased D-dimer concentrations (≥500 µg/L). Study participants with elevated D-dimer levels in comparison to subjects with levels in the reference range were significantly older, and more frequently reported a history of cardiovascular disease, hypertension, venous thromboembolism, and chronic venous insufficiency. In multivariable logistic regression analysis, CRP levels (OR 5.58 per mg/dL, 95% CI 1.77-17.60) and white blood cell count (OR 1.48 per nL, 95% CI 1.19-1.83) were significantly related to elevated D-dimers even after adjustment for multiple testing. However, acute or persistent symptoms were not significantly associated with increased D-dimers. Elevated D-dimer levels months after an acute COVID-19 disease seems to be associated with markers of inflammation. Further studies are needed to investigate the underlying pathophysiological mechanisms and consequences of prolonged D-dimer elevation in these patients.

Implication of Neutrophils Extracellular Traps in the Pathogenesis of SARS-CoV-2 pneumonia.

Peripheral blood polymorphonuclear neutrophils (PMNs) forming extracellular traps (NETs), as well as endothelial- and platelet-derived parameters, have been analyzed in patients with SARS-CoV-2 pneumonia, and their prognostic role has been evaluated. Eighty-seven consecutive patients hospitalized with SARS-CoV-2 pneumonia were prospectively selected. A sample of 30 healthy individuals served as the control group. Clinical and oxygenation (oxygen saturation to fraction of inspired oxygen ratio—SpO2/FiO2) characteristics and PMNs forming NETs, serum levels of myeloperoxidase, E-selectin, vascular cell adhesion molecule 1—VCAM1—vascular endothelial growth factor, P-selectin, platelet factor 4 and plasma concentrations of D-dimer were evaluated at hospital admission, at discharge and 14 days after discharge. Intensive care unit admission or death was the primary composite endpoint. Patients showed a higher number of PMNs forming NETs than healthy controls. The absolute number of PMNs forming NETs was inversely correlated with oxygen status (SpO2/FiO2) and positively with inflammatory (C-reactive protein, ferritin) markers and VCAM1. A decrease in, but not a normalization of NETs and endothelial-derived parameters was observed in patients who survived. In conclusion, the formation of NETs runs parallel to that of other inflammatory and endothelial activation markers, and is inverse to the oxygenation parameters, supporting a pathogenic role for PMNs in this entity.

Risk Factors, Bleeding Disorder and COVID-19 in Bamako, Mali

Introduction: Patients with COVID_19 infection have been shown to have an increased thrombotic risk, due to activation of coagulation secondary to sepsis. Objective: To study biological markers correlated with blood clotting disorders in hospitalized patients with COVID_19. Method: This was a retrospective descriptive and analytical cross-sectional study conducted at the Mali Hospital between September 2020 and January 2021. The markers being biologically monitored were: PT, ACT, INR, D-dimer and Troponin-I. Result: A total of 134 patients were enrolled in our study. Male was in the majority than female with 62.68% male and 37.31% female. The age group from 20 to 50 years was the most represented, at 58.21%. Biological markers showed plasma D-dimer concentration &gt; 0.5 μL, PT ˂ 70, INR &gt; 3; an ACT &gt; 40 seconds and a Troponin &gt; 0.1 μL for 76.11%, 10.44%, 15.67%, 16.41% and 1.49% of the study population respectively. The rate of cured patients was 94.02% and that of deceased patients was 5.97%, with all deceased patients having a high D-dimer level. Conclusion: Blood clotting disorders and elevated D-Dimer are important biomarkers predicting complications of COVID_19 infection.