Utility and limitations of patient-adjusted D-dimer cut-off levels for diagnosis of venous thromboembolism-A systematic review and meta-analysis.

PURPOSE: To systematically assess test performance of patient-adapted D-dimer cut-offs for the diagnosis of venous thromboembolism (VTE). METHODS: Systematic review and analysis of articles published in PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases. Investigations assessing patient-adjusted D-dimer thresholds for the exclusion of VTE were included. A hierarchical summary receiver operating characteristic model was used to assess diagnostic accuracy. Risk of bias was assessed by Quality Assessment of Diagnostic Accuracy Studies 2 score. RESULTS: A total of 68 studies involving 141,880 patients met the inclusion criteria. The standard cut-off revealed a sensitivity of 0.99 (95% confidence interval [CI] 0.98-0.99) and specificity of 0.23 (95% CI 0.16-0.31). Sensitivity was comparable to the standard cut-off for age-adjustment (0.97 [95% CI 0.96-0.98]) and YEARS algorithm (0.98 [95% CI 0.91-1.00]) but lower for pretest probability (PTP)-adjusted (0.95 [95% CI 0.89-0.98) and COVID-19-adapted thresholds (0.93 [95% CI 0.82-0.98]). Specificity was significantly higher across all adjustment strategies (age: 0.43 [95% CI 0.36-0.50]; PTP: 0.63 [95% CI 0.51-0.73]; YEARS algorithm: 0.65 [95% CI 0.39-0.84]; and COVID-19: 0.51 [95% CI 0.40-0.63]). The YEARS algorithm provided the best negative likelihood ratio (0.03 [95% CI 0.01-0.15]), followed by age-adjusted (both 0.07 [95% CI 0.05-0.09]), PTP (0.08 [95% CI 0.04-0.17), and COVID-19-adjusted thresholds (0.13 [95% CI 0.05-0.32]). CONCLUSIONS: This study indicates that adjustment of D-dimer thresholds to patient-specific factors is safe and embodies considerable potential for reduction of imaging. However, robustness, safety, and efficiency vary considerably among different adjustment strategies with a high degree of heterogeneity.

D-dimer testing: A narrative review.

D-dimer containing species are soluble fibrin degradation products derived from plasmin-mediated degradation of cross-linked fibrin, i.e., 'D-dimer'. D-dimer can hence be considered a biomarker of in vivo activation of both coagulation and fibrinolysis, the leading clinical application in daily practice of which is ruling out venous thromboembolism (VTE). D-dimer has been further evaluated for assessing the risk of VTE recurrence and helping define optimal duration of anticoagulation treatment in VTE, for diagnosing disseminated intravascular coagulation (DIC), and for screening those at enhanced risk of VTE. D-dimer assays should however be performed as intended by regulatory agencies, as their use outside these indications might make them a laboratory-developed test (LDT). This narrative review is aimed at: (1) reviewing the definition of D-dimer, (2) discussing preanalytical variables affecting D-dimer measurement, (3) reviewing and comparing the assays performance and some postanalytical variables (e.g., different units and age-adjusted cutoffs), and (4) discussing the interest of D-dimer measurement across different clinical settings, including pregnancy, cancer, and coronavirus disease 2019 (COVID-19).

Association of inflammatory and coagulation biomarkers with mortality in patients aged 60 years or older and hospitalized with COVID-19 / Associação entre biomarcadores inflamatórios e da coagulação com mortalidade em pacientes com 60 anos de idade ou mais hospitalizados com COVID-19

Objectives: To analyze the association of inflammatory and coagulation biomarkers with mortality in geriatric patients with COVID-19. Methods: This is a retrospective cohort study of 206 patients aged 60 years or older who were hospitalized with COVID-19 at an intensive care unit. The analyzed variables were age, sex, length of hospital stay, and inflammatory biomarkers (C-reactive protein, neutrophil-to-lymphocyte ratio, procalcitonin, fibrinogen, ferritin, and d-dimer). We constructed a receiver operating characteristic curve and analyzed the area under the curve to evaluate the accuracy of biomarkers associated with mortality in patients with COVID-19. Results: Mean age was 72 (± 8) years. There were 101 deaths (49% of the total sample), which were significantly more frequent (p = 0.006) in the older age groups and were distributed as follows: 37.50% (60 ­ 69 years old); 50% (70 ­ 79 years old); 67.50% (80 ­ 89 years old); and 75% (over 90 years old). Mortality was associated with increased serum levels of procalcitonin, neutrophil-to-lymphocyte ratio, C-reactive protein, and d-dimer, and decreased fibrinogen levels. Neutrophil-to-lymphocyte ratio occupied the largest area under the receiver operating characteristic curve (area under the curve 0.859) in this group. Conclusions: In this study, inflammatory biomarkers neutrophil-to-lymphocyte ratio, procalcitonin, C-reactive protein, and d-dimer were associated with mortality in older patients with COVID-19 hospitalized at an intensive care unit, and neutrophil-to-lymphocyte ratio presented the best accuracy.

Objetivos: Analisar associação de biomarcadores inflamatórios e da coagulação com mortalidade em pacientes geriátricos com COVID-19. Metodologia: Estudo do tipo coorte retrospectiva de 206 pacientes com 60 anos de idade ou mais internados em unidade de terapia intensiva (UTI) com COVID-19. As variáveis analisadas foram idade, sexo, tempo de permanência hospitalar e biomarcadores inflamatórios, sendo esses proteína C reativa (PCR), relação neutrófilo-linfócitos (RNL), procalcitonina, fibrinogênio, ferritina e D-dímero. Empregou-se a curva ROC, com análise da área sob a curva (ACR), para avaliar a acurácia dos biomarcadores associados à mortalidade nos pacientes com COVID-19. Resultados: A média de idade foi de 72 (± 8) anos. Ocorreram 101 óbitos (49,02% da amostra total), significativamente mais frequente (p = 0,006) nas faixas etárias mais elevadas, distribuídos por faixa etária: 37,50% (60 ­ 69 anos); 50% (70 ­ 79 anos); 67,50% (80 ­ 89 anos); e 75% (nos maiores de 90 anos). A mortalidade foi associada a aumento dos níveis séricos dos biomarcadores procalcitonina, relação neutrófiloslinfócitos (RNL), proteína C reativa (PCR) e D-dímero, bem como diminuição dos níveis de fibrinogênio. A RNL ocupou a maior área sob a curva ROC (ACR 0,859) nesse grupo. Conclusões: Neste estudo, os biomarcadores inflamatórios RNL, procalcitonina, PCR e D-dímero foram associados com mortalidade em pacientes idosos portadores de COVID-19 internados em UTI, e a RNL foi a que apresentou a melhor acurácia.

COVID-19 and stroke: from the cases to the causes.

During COVID-19 pandemic, a wide variety of stroke typologies have been described in patients affected by SARS-CoV-2. Investigating the case reports of acute stroke in COVID-19 patients, published since the beginning of the pandemic, we tried to trace the pathogenic mechanisms of stroke during SARS-CoV-2 infection. We conducted a systematic review analyzing demographic data, cerebrovascular risk factors, NIHSS score, vascular territory involvement and laboratory findings of 168 patients described in 89 studies, from a pool of 1243 records. Based on our results, we have identified different stroke profiles: (1) cerebral large vessel disease (CLVD) profile with a low disability, simultaneous onset of COVID-19 and stroke symptoms, good outcome and low serum levels of D-dimer and CRP; (2) intracranial bleeding (IB) profile with high disability, poor outcome and low levels of serum markers of inflammation and coagulopathy; (3) CLVD profile with a short time-lapse between COVID-19 symptoms and stroke onset, high neurological disability and very high systemic inflammatory markers; (4) multiple thrombo-embolic disease (MTED) profile with older patients, many comorbidities, disabling stroke, poor outcome, evident alteration of coagulation tests and high serum levels of both D-dimer and CRP. We therefore summarized these different profiles in a spectrum similar to that of visible light, where the violet-blue band included IB and CSVD with low inflammation and prothrombotic activity, the green-yellow band included CLVD with high inflammation and moderate prothrombotic activity and the orange-red band for MTED with moderate-high levels of inflammation and very high prothrombotic activity.

Pulmonary embolism in COVID-19, risk factors and association with inflammatory biomarkers.

The coronavirus disease 2019 (COVID-19) pandemic affected millions of people worldwide resulting in a substantial number of hospitalizations. Venous thromboembolism including pulmonary embolism is a known complication of COVID-19 pneumonia although its incidence in such patients is unclear. In this multicenter retrospective cohort study, we looked at the incidence of pulmonary embolism in COVID-19 patients and its associations with various risk factors including demographics, comorbidities, inflammatory markers and coagulation profiles. We analyzed data from 193 patients of mixed ethnicity with a mean age of 51, mostly South Asians (62%) and Arabs (29%). Diabetes and hypertension were the most prevalent comorbidities accounting for 46% (N = 88) and 36% (N = 71) respectively. Critical COVID-19 illness was diagnosed in 67% of patients. The frequency of COVID-19 related pulmonary embolism was 21.8% (N = 42). We found no association of pulmonary embolism with demographic, comorbid or inflammatory variables. Only a raised D-Dimer was found to be associated with pulmonary embolism. Having a pulmonary embolism had no impact on the length of stay, critical illness, or mortality. Receiving steroids or being on standard thromboprophylaxis or weight/D-Dimer adjusted thromboprophylaxis also had no impact on the frequency of pulmonary embolism. Nine incidents of major bleeding were recorded independent of therapeutic anticoagulation. Patients admitted to the hospital for COVID-19 pneumonia had a relatively high incidence of pulmonary embolism. D-dimer was the only associated laboratory parameter associated with pulmonary embolism. However, further research is needed to evaluate its predictive and prognostic utility, particularly in an older population.

CVD22: Explainable artificial intelligence determination of the relationship of troponin to D-Dimer, mortality, and CK-MB in COVID-19 patients.

BACKGROUND AND PURPOSE: COVID-19, which emerged in Wuhan (China), is one of the deadliest and fastest-spreading pandemics as of the end of 2019. According to the World Health Organization (WHO), there are more than 100 million infectious cases worldwide. Therefore, research models are crucial for managing the pandemic scenario. However, because the behavior of this epidemic is so complex and difficult to understand, an effective model must not only produce accurate predictive results but must also have a clear explanation that enables human experts to act proactively. For this reason, an innovative study has been planned to diagnose Troponin levels in the COVID-19 process with explainable white box algorithms to reach a clear explanation. METHODS: Using the pandemic data provided by Erzurum Training and Research Hospital (decision number: 2022/13-145), an interpretable explanation of Troponin data was provided in the COVID-19 process with SHApley Additive exPlanations (SHAP) algorithms. Five machine learning (ML) algorithms were developed. Model performances were determined based on training, test accuracies, precision, F1-score, recall, and AUC (Area Under the Curve) values. Feature importance was estimated according to Shapley values by applying the SHApley Additive exPlanations (SHAP) method to the model with high accuracy. The model created with Streamlit v.3.9 was integrated into the interface with the name CVD22. RESULTS: Among the five-machine learning (ML) models created with pandemic data, the best model was selected with the values of 1.0, 0.83, 0.86, 0.83, 0.80, and 0.91 in train and test accuracy, precision, F1-score, recall, and AUC values, respectively. As a result of feature selection and SHApley Additive exPlanations (SHAP) algorithms applied to the XGBoost model, it was determined that DDimer mean, mortality, CKMB (creatine kinase myocardial band), and Glucose were the features with the highest importance over the model estimation. CONCLUSIONS: Recent advances in new explainable artificial intelligence (XAI) models have successfully made it possible to predict the future using large historical datasets. Therefore, throughout the ongoing pandemic, CVD22 (https://cvd22covid.streamlitapp.com/) can be used as a guide to help authorities or medical professionals make the best decisions quickly.

Systematic screening versus clinical gestalt in the diagnosis of pulmonary embolism in COVID-19 patients in the emergency department.

BACKGROUND: Diagnosing concomitant pulmonary embolism (PE) in COVID-19 patients remains challenging. As such, PE may be overlooked. We compared the diagnostic yield of systematic PE-screening based on the YEARS-algorithm to PE-screening based on clinical gestalt in emergency department (ED) patients with COVID-19. METHODS: We included all ED patients who were admitted because of COVID-19 between March 2020 and February 2021. Patients already receiving anticoagulant treatment were excluded. Up to April 7, 2020, the decision to perform CT-pulmonary angiography (CTPA) was based on physician's clinical gestalt (clinical gestalt cohort). From April 7 onwards, systematic PE-screening was performed by CTPA if D-dimer level was ≥1000 ug/L, or ≥500 ug/L in case of ≥1 YEARS-item (systematic screening cohort). RESULTS: 1095 ED patients with COVID-19 were admitted. After applying exclusion criteria, 289 were included in the clinical gestalt and 574 in the systematic screening cohort. The number of PE diagnoses was significantly higher in the systematic screening cohort compared to the clinical gestalt cohort: 8.2% vs. 1.0% (3/289 vs. 47/574; p<0.001), even after adjustment for differences in patient characteristics (adjusted OR 8.45 (95%CI 2.61-27.42, p<0.001) for PE diagnosis). In multivariate analysis, D-dimer (OR 1.09 per 1000 µg/L increase, 95%CI 1.06-1.13, p<0.001) and CRP >100 mg/L (OR 2.78, 95%CI 1.37-5.66, p = 0.005) were independently associated with PE. CONCLUSION: In ED patients with COVID-19, the number of PE diagnosis was significantly higher in the cohort that underwent systematic PE screening based on the YEARS-algorithm in comparison with the clinical gestalt cohort, with a number needed to test of 7.1 CTPAs to detect one PE.

Discrepancy between biomarkers of lung injury and 1-year mortality in COVID-19.

BACKGROUND: COVID-19 global pandemic started in late 2019 with the first wave. In this cross-sectional and observational study, we evaluated the associations between the biomarkers, COVID-19 pneumonia severity and 1-year mortality. METHODS: A sample of 276 polymerase chain reaction (PCR)-positive patients for SARS-CoV-2 was included. Computerized tomography severity score (CT-SS) was used to assess the severity of COVID-19 pneumonia in 222 cases. Multivariate analyses were performed to find the predictors of CT-SS, severe CT-SS (≥20) and 1-year mortality. Biomarkers of ferritin, high-sensitive C-reactive protein (CRP), lactate dehydrogenase (LDH), cardiac troponin (cTn), neutrophil-to-lymphocyte ratio (NLR), uric acid (UA) and d-dimer were routinely measured. RESULTS: Severe CT-SS (>20) was observed in 86 (31.2%) cases. Mortality was observed in 75 (27.2%) patients at 1 year. LDH displayed the highest predictive accuracy for severe CT-SS (AUC 0.741, sensitivity = 81% and specificity = 68%, cut-off value: 360 mg/dl). Linear regression analysis displayed that LDH predicted CT-SS [B = 11 (95% CI for B = 5-17, p < .001)]. Age was the most significant parameter that was associated with severe CT-SS (OR 0.96, 95% CI 0.92-0.99, p = .015). d-dimer was the only biomarker that predicted with 1-year mortality (OR 1.62, 95% CI 1.08-2.42, p = .020). CONCLUSION: LDH is a sensitive and specific biomarker to determine patients with severe lung injury in COVID-19. d-dimer is the only biomarker that predicts 1-year mortality. Neither LDH nor CT-SS is associated with 1-year mortality.

Performance of D-dimer to lymphocyte ratio in predicting the mortality of COVID-19 patients.

Background: Nowadays, there is still no effective treatment developed for COVID-19, and early identification and supportive therapies are essential in reducing the morbidity and mortality of COVID-19. This is the first study to evaluate D-dimer to lymphocyte ratio (DLR) as a prognostic utility in patients with COVID-19. Methods: We retrospectively analyzed 611 patients and separated them into groups of survivors and non-survivors. The area under the curve (AUC) of various predictors integrated into the prognosis of COVID-19 was compared using the receiver operating characteristic (ROC) curve. In order to ascertain the interaction between DLR and survival in COVID-19 patients, the Kaplan-Meier (KM) curve was chosen. Results: Age (OR = 1.053; 95% CI, 1.022-1.086; P = 0.001), NLR (OR = 1.045; 95% CI, 1.001-1.091; P = 0.046), CRP (OR = 1.010; 95% CI, 1.005-1.016; P < 0.001), PT (OR = 1.184; 95% CI, 1.018-1.377; P = 0.029), and DLR (OR = 1.048; 95% CI, 1.018-1.078; P = 0.001) were the independent risk factors related with the mortality of COVID-19. DLR had the highest predictive value for COVID-19 mortality with the AUC of 0.924. Patients' survival was lower when compared to those with lower DLR (Log Rank P <0.001). Conclusion: DLR might indicate a risk factor in the mortality of patients with COVID-19.

D-dimer levels in non-COVID-19 ARDS and COVID-19 ARDS patients: A systematic review with meta-analysis.

BACKGROUND: Hypercoagulability and thrombo-inflammation are the main reasons for death in COVID-19 patients. It is unclear whether there is a difference between D-dimer levels in patients without or with COVID-19 acute respiratory distress syndrome (ARDS). METHODS: We searched PubMed, EMBASE, and ClinicalTrails.gov databases looking for studies reporting D-dimer levels in patients without or with COVID-19 ARDS. Secondary endpoints included length of hospital stay, and mortality data at the longest follow-up available. RESULTS: We included 12 retrospective and 3 prospective studies with overall 2,828 patients, of whom 1,404 (49.6%) had non-COVID-19 ARDS and 1,424 had COVID-19 ARDS. D-dimer levels were not significantly higher in non-COVID-19 ARDS than in COVID-19 ARDS patients (mean 7.65 mg/L vs. mean 6.20 mg/L MD 0.88 [CI: -0.61 to 2.38] p = 0.25; I² = 85%) while the length of hospital stay was shorter (non-COVID-19 mean 37.4 days vs. COVID-19 mean 48.5 days, MD -10.92 [CI: -16.71 to -5.14] p < 0.001; I² = 44%). No difference in mortality was observed: non-COVID-19 ARDS 418/1167 (35.8%) vs. COVID-19 ARDS 467/1201 (38.8%). CONCLUSIONS: We found no difference in the mean D-dimer levels between non-COVID-19 ARDS and COVID-19 ARDS patients.

Dynamic coagulofibrinolytic responses under long-term VV-ECMO management without anticoagulation in a COVID-19-ARDS patient: A case report.

RATIONALE: Venovenous extracorporeal membrane oxygenation (ECMO) is recommended for the treatment of critically ill patients with acute respiratory distress syndrome due to coronavirus disease 2019 (COVID-19). However, ECMO management can cause both bleeding and thrombotic complications. There are insufficient coagulofibrinolytic data for appropriate ECMO management in patients with COVID-19. PATIENT CONCERNS: A 48-year-old man with severe COVID-19-acute respiratory distress syndrome underwent long-term venovenous ECMO management for 48 days. Refractory oronasal bleeding developed on day 13, so the administration of unfractionated heparin was ceased for 29 days. DIAGNOSIS: The patient showed dynamic coagulofibrinolytic responses associated with ECMO management, as shown by fibrin/fibrinogen degradation products, soluble fibrin, thrombin-antithrombin complex, and plasmin-α2-plasmin inhibitor complex elevations, suggesting the development of ECMO-induced coagulopathy. INTERVENTIONS: We assessed coagulofibrinolytic markers to decide the appropriate timing for controlling excessive activation of coagulation by exchanging ECMO circuits. Moreover, viscoelastic hemostatic assays were used for adequate transfusion of blood products. OUTCOMES: Safe long-term ECMO management was completed, which was withdrawn on day 48. The patient was weaned off mechanical ventilation on day 57 and was transferred to another hospital for rehabilitation. LESSONS: Monitoring the coagulofibrinolytic status using markers and viscoelastic hemostatic assays may be effective for safe long-term ECMO management even without anticoagulant therapy.

Neutrophil count multiplied by D-dimer combined with pneumonia may better predict short-term outcomes in patients with acute ischemic stroke.

OBJECTIVE: To investigate the predictive value of neutrophil, D-dimer and diseases associated with stroke for short-term outcomes of acute ischemic stroke (AIS). METHODS: By collecting the subitems of laboratory data especially routine blood and coagulation test in AIS patients, and recording their clinical status, the correlation, regression and predictive value of each subitem with the short-term outcomes of AIS were analyzed. The predict model was constructed. RESULTS: The neutrophil count multiplied by D-dimer (NDM) had the best predictive value among the subitems, and the area under the receiver operating characteristic (ROC) curve reached 0.804. When clinical information was not considered, the Youden index of NDM was calculated to be 0.48, corresponding to an NDM value of 7.78, a diagnostic sensitivity of 0.79, specificity of 0.69, negative predictive value of 96%. NDM were divided into 5 quintiles, the five grade of NDM (quintile) were < = 1.82, 1.83-2.41, 2.42-3.27, 3.28-4.49, 4.95+, respectively. The multivariate regression analysis was conducted between NDM (quintile), Babinski+, pneumonia, cardiac disease and poor outcomes of AIS. Compared with the first grade of NDM (quintile), the second grade of NDM (quintile) was not significant, but the third grade of NDM (quintile) showed 7.061 times, the fourth grade of NDM (quintile) showed 11.776 times, the fifth grade of NDM (quintile) showed 23.394 times in short-term poor outcomes occurrence. Babinski sign + showed 1.512 times, pneumonia showed 2.995 times, cardiac disease showed 1.936 times in short-term poor outcomes occurrence compared with those negative patients. CONCLUSIONS: NDM combined with pneumonia may better predict short-term outcomes in patients with AIS. Early prevention, regular examination and timely intervention should be emphasized for patients, which may reduce the risk of short-term poor outcomes.

Point-of-Care Platform for Diagnosis of Venous Thrombosis by Simultaneous Detection of Thrombin Generation and D-Dimer in Human Plasma.

Venous thromboembolism (VTE) refers to a blood clot that starts in a vein. The risk of developing VTE is highest after major surgery or a major injury, or when someone has heart failure, cancer, or infectious disease (e.g., COVID-19). Without prompt treatment to break up clots and prevent more from forming, VTE can restrict or block blood flow and oxygen, which can damage the body tissue or organs. VTE can occur without any obvious signs, and imaging technologies are used. Alternatively rapid measurement of thrombin generation (TG) and D-dimer could be used to make a fast, portable, and easy-to-use diagnostic platform for VTE. Here, we have demonstrated a diagnostic sensing platform with the ability of simultaneous detection of TG and D-dimer in human plasma. Modifications were made to both the assay protocols to eliminate the need for sample dilution and incubation steps. Using a substantially reduced sample volume, the measurement results show comparable performance to the gold standard method. Our platform is able to deliver accurate and cost-effective results for both TG and D-dimer assays when using undiluted plasma in under 15 min. The assays presented are therefore a good candidate technology for use in a point-of-care platform to diagnose VTE.

Prognostic association between d-dimer thresholds and 30-day pulmonary embolism diagnosis among emergency department patients with suspected SARS-CoV-2 infection: a Canadian COVID-19 Emergency Department Rapid Response Network study.

OBJECTIVE: The primary objective was to quantify the prognostic association between various D-dimer thresholds and 30-day PE diagnosis among emergency department (ED) patients with suspected SARS-CoV-2 infection. METHODS: This was a retrospective study of patients enrolled in the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) registry from March 1, 2020 to July 2, 2021. We included consecutive adults (≥ 18 years) presenting to 49 EDs with chest pain, shortness of breath, hypoxia, syncope, presyncope, or hemoptysis who were tested for both SARS-CoV-2 and D-dimer at index ED visit. The primary outcome measure was the sensitivity, specificity, and negative predictive value of D-dimer test thresholds for the outcome of 30-day PE diagnosis. RESULTS: Among 10,837 patients included in our study, 404 (3.7%) were diagnosed with PE at 30-days. A standard D-Dimer threshold of 500 ng/mL had a sensitivity of 97.8% (95% confidence interval [CI] 95.8-99.0%), specificity of 40.9% (95% CI 39.9-41.8%), and negative predictive value of 99.8% (95% CI 99.6-99.9%). An age-adjusted D-dimer threshold had a sensitivity of 96.0% (95% CI 93.6-97.7%), specificity of 48.5% (95% CI 47.5-49.4%), and negative predictive value of 99.7% (95% CI 99.5-99.8%). D-dimer testing had slightly lower prognostic performance among SARS-CoV-2 positive compared to SARS-CoV-2 negative patients in predicting 30-day PE diagnosis. CONCLUSIONS: Among ED patients with suspected SARS-CoV-2, the standard 500 ng/mL and age-adjusted D-dimer thresholds were comparable for the prediction of PE at 30-days. The prognostic performance of D-dimer was lower among SARS-CoV-2 positive patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04702945.

RéSUMé: OBJECTIF: L'objectif principal était de quantifier l'association pronostique entre différents seuils de D-dimères et le diagnostic d'EP à 30 jours chez les patients des services d'urgence suspectés d'être infectés par le SRAS-CoV-2. MéTHODES: Il s'agissait d'une étude rétrospective des patients inscrits au registre du réseau canadien de réponse rapide aux urgences COVID-19 (CCEDRRN) du 1er mars 2020 au 2 juillet 2021. Nous avons inclus des adultes consécutifs (>18 ans) se présentant dans 49 services d'urgence pour une douleur thoracique, un essoufflement, une hypoxie, une syncope, une présyncope ou une hémoptysie et qui ont été testés à la fois pour le SRAS-CoV-2 et les D-dimères lors de la visite de référence aux urgences. Le principal critère d'évaluation était la sensibilité, la spécificité et la valeur prédictive négative des seuils du test des D-dimères pour le diagnostic de l'EP à 30 jours. RéSULTATS: Parmi les 10 837 patients inclus dans notre étude, 404 (3,7 %) ont reçu un diagnostic d'EP à 30 jours. Un seuil standard de D-Dimer de 500 ng/mL avait une sensibilité de 97,8 % (intervalle de confiance [IC] à 95 % 95,8-99,0 %), une spécificité de 40,9 % (IC à 95 % 39,9-41,8 %) et une valeur prédictive négative de 99,8 % (IC à 95 % 99,6-99,9 %). Un seuil de D-dimères ajusté à l'âge avait une sensibilité de 96,0% (IC à 95 % 93,6-97,7 %), une spécificité de 48,5% (IC à 95 % 47,5-49,4 %) et une valeur prédictive négative de 99,7 % (IC à 95 % 99,5-99,8 %). Le test des D-dimères avait une performance pronostique légèrement inférieure chez les patients positifs pour le SRAS-CoV-2 par rapport aux patients négatifs pour le SRAS-CoV-2 en ce qui concerne la prédiction du diagnostic d'EP à 30 jours. CONCLUSIONS: Chez les patients des urgences suspectés d'être atteints du SRAS-CoV-2, les seuils standard de 500 ng/ml et les seuils de D-dimères ajustés à l'âge étaient comparables pour la prédiction de l'EP à 30 jours. La performance pronostique des D-dimères était plus faible chez les patients positifs pour le SRAS-CoV-2. ENREGISTREMENT DE L'ESSAI: Clinicaltrials.gov, NCT04702945.

Pathomechanisms Underlying Hypoxemia in Two COVID-19-Associated Acute Respiratory Distress Syndrome Phenotypes: Insights From Thrombosis and Hemostasis.

BACKGROUND: The pathomechanisms of hypoxemia and treatment strategies for type H and type L acute respiratory distress syndrome (ARDS) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) have not been elucidated. MAIN TEXT: SARS-CoV-2 mainly targets the lungs and blood, leading to ARDS, and systemic thrombosis or bleeding. Angiotensin II-induced coagulopathy, SARS-CoV-2-induced hyperfibrin(ogen)olysis, and pulmonary and/or disseminated intravascular coagulation due to immunothrombosis contribute to COVID-19-associated coagulopathy. Type H ARDS is associated with hypoxemia due to diffuse alveolar damage-induced high right-to-left shunts. Immunothrombosis occurs at the site of infection due to innate immune inflammatory and coagulofibrinolytic responses to SARS-CoV-2, resulting in microvascular occlusion with hypoperfusion of the lungs. Lung immunothrombosis in type L ARDS results from neutrophil extracellular traps containing platelets and fibrin in the lung microvasculature, leading to hypoxemia due to impaired blood flow and a high ventilation/perfusion (VA/Q) ratio. COVID-19-associated ARDS is more vascular centric than the other types of ARDS. D-dimer levels have been monitored for the progression of microvascular thrombosis in COVID-19 patients. Early anticoagulation therapy in critical patients with high D-dimer levels may improve prognosis, including the prevention and/or alleviation of ARDS. CONCLUSIONS: Right-to-left shunts and high VA/Q ratios caused by lung microvascular thrombosis contribute to hypoxemia in type H and L ARDS, respectively. D-dimer monitoring-based anticoagulation therapy may prevent the progression to and/or worsening of ARDS in COVID-19 patients.

Venous thromboembolism in COVID-19: A meta-summary of cases.

OBJECTIVES: To summarize cases of venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT) among coronavirus disease (COVID-19) patients and discuss their symptoms, diagnostic method, clinical features, and prognosis. METHODS: All major databases were searched for relevant studies published between December 1, 2019 and May 5, 2021. RESULTS: A total of 233 articles were identified, 22 describing 48 patients were included. A total of 79.1% had PE and 20.9% had DVT. Most patients were men, with a mean age of 56 years. Comorbidities were present in 70.8%, and 85.4% had at least one risk factor of VTE. 56.3% had received anticoagulation therapy. Most patients were treated in the general ward. Complications occurred in 27.1% of the patients, and recovery was achieved in 80.4%. CONCLUSION: Venous thromboembolism must be suspected even in patients who had received prior anticoagulant regimens or in stable cases, especially in males, the elderly, and patients with comorbidities and high D-dimer levels.

A novel combined index of D-dimer, fibrinogen, albumin, and platelet (FDAPR) as mortality predictor of COVID-19.

Background: In coronavirus disease 2019 (COVID-19) caused by SARSCoV2 viruses, coagulation abnormalities are strongly correlated between disease severity and mortality risk. Aims: The aim was to search for new indices to determine mortality risk. Fibrinogen times D-dimer to albumin times platelet ratio calculated with the formula (FDAPR index: ((Fibrinogen × D-dimer)/(Albumin × Platelet)) investigated as a mortality marker in COVID-19 patients. The hospitalization data of 1124 patients were analyzed from the electronic archive system. Hemogram, coagulation, and inflammatory markers were investigated in the study group. Materials and Methods: All statistical analyses like the student t-test, Mann-Whitney U, Kaplan-Meier, and Cox hazard ratio, were performed with the SPSS 22.0 program. Results: Prothrombin time was prolonged significantly in patients (P < 0.05) compared to healthy subjects (n = 30). D-dimer and fibrinogen were high, and albumin and platelet counts were low in COVID-19 patients (all, P < 0.001). When the data of 224 non-survivors and 900 survived patients were compared, D-dimer and fibrinogen were higher, and albumin and platelet lower (all, P < 0.001) compared to mild and severe patients. At the cut-off value of 0.49, the FDAPR index was performed with 89.1% sensitivity and 88.6% specificity. FDAPR index had the highest mortality predictive power (P < 0.01; HR = 5.366; 95% CI; 1.729-16.654). Conclusions: This study revealed that the FDAPR index could be used as a mortality marker of COVID-19 disease.

The Prediction Value of D-Dimer on Prognosis in Intensive Care Unit among Old Patients ( ≥65 Years): A 9-Year Single-Center Retrospective Study of 9261 Cases.

Background: D-dimer (DD) has been indicated as a potential indicator due to its connection with the prognosis of the COVID-19 pandemic. Aging is linked to elevated DD levels in coagulation activation. However, few studies have investigated the correlation of DD with prognosis, especially in the old population. Therefore, this study aims at investigating the correlation of DD with prognosis in shock and perioperative populations over 65 years of age. Methods: We analyzed 9261 old patients admitted to intensive care units (ICUs) with either confirmed shock or in perioperative period of high-risk surgery, with 8813 of them had DD levels determined on admission. In-hospital mortality, length of ICU stay and ventilation time (VT) associated variables were assessed using generalized linear models. Results: Although DD levels had no positive correlations with in-hospital mortality (RR, 1.006; 95% CI, 0.998-1.014) and length of ICU stay (RR, 1.012; 95% CI, 0.997-1.028) in Model 3, they were strongly correlated with VT (RR, 1.577; 95% CI, 1.024-2.064). Higher DD levels in females (RR, 1.804; 95% CI, 1.116-2.602), those who used antibiotics (RR, 1.736; 95% CI, 1.092-2.453), those with surgery (RR, 1.640; 95% CI, 1.273-2.114), and those with shock (RR, 1.740; 95% CI, 1.001-2.687) had stronger correlation with longer VT than the counterparts. While patients who were between 65 and 74 years old (RR, 1.023; 95% CI, 1.003-1.043), with no use of antibiotics (RR, 1.007; 95% CI, 1.001-1.013) nor shock (RR, 1.011; 95% CI, 1.002-1.021), but had undergone surgical procedures (RR, 1.030; 95% CI, 1.012-1.048) were correlated with a longer ICU length of stay. Conclusion: DD levels at ICU admission are highly related to increased VT and length of ICU stay in the old population with either confirmed shock or after high-risk surgery, indicating the strong potential of DD as a marker with prognostic utility for all ICU patients in the future.