scholarly journals NEUT-SFL in Patients with COVID-ARDS: A Novel Biomarker for Thrombotic Events?

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Laure Stiel ◽  
Yannick Rabouel ◽  
Agathe Debliquis ◽  
Valentin Pointurier ◽  
Joy Mootien ◽  
...  

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA virus first identified in December 2019 in Wuhan, China, and responsible for coronavirus disease 2019 (COVID-19). The ongoing COVID-19 pandemic is impacting healthcare worldwide. Patients who develop coagulopathy have worse outcomes. The pathophysiology of COVID-19 suggests a strong interplay between hemostasis and immune cells, especially neutrophils. Our purpose was to assess neutrophil fluorescence as a potential biomarker of deep vein thrombosis (DVT) in patients with COVID-acute respiratory distress syndrome (COVID-ARDS). Sixty-one patients with COVID-ARDS admitted to the four intensive care units (ICUs) of a French general hospital were included in this prospective study. Neutrophil activation was assessed by measuring neutrophil fluorescence (NEUT-Side Fluorescence Light, NEUT-SFL) with a specific fluorescent dye staining analyzed by a routine automated flow cytometer Sysmex XN-3000™ (Sysmex, Kobe, Japan). DVT was diagnosed by complete duplex ultrasound (CDU). We found that NEUT-SFL was elevated on admission in patients with COVID-ARDS (49.76 AU, reference value 46.40 AU, p < 0.001 ), but did not differ between patients with DVT (49.99 AU) and those without (49.52 AU, p = 0.555 ). NEUT-SFL is elevated in patients with COVID-ARDS, reflecting neutrophil activation, but cannot be used as a marker of thrombosis. Because neutrophils are at interface between immune response and hemostasis through release of neutrophil extracellular traps, monitoring their activation could be an interesting approach to improve our management of coagulopathy during COVID-ARDS. Further research is needed to better understand the pathophysiology of COVID-19 and identify high-performance biomarkers.

2013 ◽  
Vol 12 (2) ◽  
pp. 118-122
Author(s):  
Liz Andrea Villela Baroncini ◽  
Graciliano Jose Franca ◽  
Aguinaldo de Oliveira ◽  
Enrique AntonioVidal ◽  
Carlos Eduardo Del Valle ◽  
...  

BACKGROUND: Symptoms and clinical signs suggestive of deep vein thrombosis (DVT) are common but may have numerous possible causes. OBJECTIVES: 1) To identify the most frequent clinical symptoms and correlate them with duplex ultrasound scan (DS) findings; 2) to identify high-risk clinical conditions for DVT; and 3) to evaluate time since the onset of symptoms and DS examination. METHODS: A total of 528 patients with a clinical suspicion of DVT were evaluated by DS performed by experienced vascular ultrasonographists. RESULTS: DVT was present in 192 (36.4%) of the patients. The external iliac vein was involved in 53 patients (10.04%), the femoral veins in 110 (20.83%), the popliteal vein in 124 (23.48%), and veins below the knee were involved in 157 (29.73%) of the cases. Limb swelling was present in 359 cases (68%), and 303 (57.4%) complained of pain. Sixty nine patients received a DS due to suspected or proven pulmonary embolism (PE); 79 patients were in postoperative period. In the multivariate analysis, independent risk factors for DVT included age>65 years (OR=1.49; 95% confidence interval [95%CI] 1.01-2.18; p=0.042), edema (OR=2.83; 95%CI 1.72-4.65; p<0.001), pain (OR=1.99; 95%CI 1.3-3.05; p=0.002), cancer (OR=2.32; 95%CI 1.45-3.72; p<0.001), and PE (OR=2.62; 95%CI 1.29-5.32; p=0.008).Time since the onset of symptoms did not differ between the groups. CONCLUSIONS: In the present study, 36.4% of the patients referred to DS had DVT. Age > 65 years, presence of limb swelling, pain, cancer, and suspected or proven PE should be considered as major risk factors for DVT.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-10
Author(s):  
Danielle Vlazny ◽  
Damon E. Houghton ◽  
Ryan Meverden ◽  
Paul Daniels ◽  
Matthew Bartlett ◽  
...  

Background: Popliteal fossa cysts (PFCs aka Baker's cysts) are synovial cysts of the knee joint that can be symptomatic or asymptomatic and incidentally identified on ultrasound. Whether PFCs are associated with deep vein thrombosis (DVT) is unknown. Possible mechanisms for an association include direct compression of the popliteal vein, indirect compression on the popliteal vein with leg flexion, adjacent inflammation of the cyst, or relative immobility due to underlying joint disease itself. Methods: Lower extremity venous Duplex ultrasound radiology reports from the inception of electronic archiving through 11/14/2019 were evaluated across the Mayo Clinic Enterprise (Rochester MN, Jacksonville, FL, Scottsdale AZ, and Mayo Clinic Health System) in patients &gt;18 years of age. Natural language processing (NLP) algorithms were created and validated to identify acute DVT (proximal or distal) and PFCs. A random sample of 1,752 ultrasound reports underwent manual review to calculate the sensitivity and specificity of the NLP algorithm. Cases (ultrasounds with acute DVT) were compared to controls (ultrasound without acute DVT) to examine the frequency of PFCs. IRB approval was obtained and patients lacking Minnesota research authorization were excluded. Results: A total of 332,016 lower extremity venous ultrasounds were performed in 223,035 patients; 156,846 unilateral and 175,170 bilateral lower extremities exams. The mean age at ultrasound was 63.3 (SD 16.5) and 54.7% were female. Ultrasound reports were available for analysis starting in 1992 with a significant increase in the number of ultrasounds performed over the study period across the enterprise (Figure 1). Overall, acute DVT was identified in 24,179 (7.3%) of ultrasounds, and PFCs were identified in 32,427 (9.8%) of ultrasounds. The sensitivity and specificity of the NLP algorithm in the full dataset to identify acute DVT was 86.0% and 97.2%, respectfully. The sensitivity and specificity of the NLP algorithm to identify PFCs was 97.8% and 99.5%, respectively. PFCs were present in 9.3% of ultrasounds with acute DVT and 9.8% of ultrasounds without acute DVT (p=0.007), OR 0.94 (95% CI 0.90-0.98). In a multivariate logistic regression model, after adjusting for age and sex, results remained significant (aOR 0.95, 95% CI 0.91-0.995). Comparing ultrasounds before and after 2010, there was a higher percentage of PFCs and acute DVT reported after 2010 (p&lt;0.001 for both). Sensitivity analyses comparing results before or after 2010, by sex, and only in the first ultrasound performed per person, demonstrated similar results. Conclusions: PFCs are negatively associated with the presence of acute DVT on lower extremity venous Duplex ultrasound. This data does not support PFCs as a contributing or causative factor in the development of lower extremity DVT. Figure 1 Disclosures No relevant conflicts of interest to declare.


2015 ◽  
Vol 2015 ◽  
pp. 1-5
Author(s):  
Farah Al-Saffar ◽  
Ena Gupta ◽  
Furqan Siddiqi ◽  
Muhammad Faisal ◽  
Lisa M. Jones ◽  
...  

Background. We hypothesized that positive end-exploratory pressure (PEEP) may promote venous stasis in the upper extremities and predispose to upper extremity deep vein thrombosis (UEDVT).Methods. We performed a retrospective case control study of medical intensive care unit patients who required mechanical ventilation (MV) for >72 hours and underwent duplex ultrasound of their upper veins for suspected DVT between January 2011 and December 2013.Results. UEDVT was found in 32 (28.5%) of 112 patients. Nineteen (67.8%) had a central venous catheter on the same side. The mean ± SD duration of MV was13.2±9.5days. Average PEEP was7.13±2.97 cm H2O. Average PEEP was ≥10 cm H2O in 23 (20.5%) patients. Congestive heart failure (CHF) significantly increased the odds of UEDVT (OR 4.53, 95% CI 1.13–18.11;P=0.03) whereas longer duration of MV (≥13 vs. <13 days) significantly reduced it (OR 0.29, 95% CI 0.11–0.8;P=0.02). Morbid obesity showed a trend towards significance (OR 3.82, 95% CI 0.95–15.4;P=0.06). Neither PEEP nor any of the other analyzed predictors was associated with UEDVT.Conclusions. There is no association between PEEP and UEDVT. CHF may predispose to UEDVT whereas the risk of UEDVT declines with longer duration of MV.


2016 ◽  
Vol 15 (2) ◽  
pp. 63-67
Author(s):  
Bryan Renton ◽  
S Thiru ◽  
CP Griffin

Duplex scanning is utilised by many departments in the investigation of suspected Deep Vein Thrombosis (DVT). NICE Guideline CG144 recommended repeat scanning for patients in whom the initial Wells score was ‘likely’ in the presence of a raised D-Dimer, following a normal first scan. Following implementation of this recommendation in our department there was a dramatic rise in the number of repeat scans being undertaken, all of which were negative for DVT. Introduction of an electronic message to the report, placing the onus back on the referring clinician to arrange repeat scan if deemed appropriate resulted in a fall in the number of scans being undertaken without impacting on patient outcome.


2005 ◽  
Vol 93 (06) ◽  
pp. 1117-1119 ◽  
Author(s):  
Samuel Goldhaber ◽  
Victor Tapson ◽  
Michael Jaff

SummaryThe objective was to investigate newly diagnosed patients with deep vein thrombosis (DVT) who received inferior vena cava filters (IVCFs). A prospective registry enrolled 5451 patients from 183 US study sites. In all patients, examination by venous duplex ultrasound confirmed the diagnosis of DVT. We collected and analyzed data on 781 patients who received an IVCF . The most frequently prescribed treatments were low–molecular-weight heparin and unfractionated heparin, which were used as a bridge to warfarin in 39% (n=2143) and 35% (n=1926) of patients, respectively. Of the total population, 781 (14%) (235 outpatients, 546 inpatients) underwent IVCF placement. The most common reasons for IVCF placement were contraindication to anticoagulation (n = 271), prophylaxis (n = 259), major bleeding related to anticoagulation therapy (n = 92), and anticoagulation failure (n = 73). Multivariate analysis revealed that patients were more likely to undergo IVCF insertion with multiple system organ failure (odds ratio [OR], 3.6; 95% CI, 1.48–8.60), previous stroke (OR, 3.2; 95% CI, 2.11–4.74), or history of pulmonary embolism (OR, 2.4; 95% CI, 1.95–2.91). In conclusion, a surprisingly high 14% (781) of patients with confirmed DVT received an IVCF. Many of these patients may have warranted less invasive methods of venous thromboembolism prophylaxis. Improved physician education regarding mechanical and pharmacologic prophylaxis alternatives might reduce the use of IVCFs.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 274-274
Author(s):  
Mandy N. Lauw ◽  
Frank W.G. Leebeek ◽  
Moniek P.M. de Maat ◽  
Gerard J. van Mierlo ◽  
Saskia Middeldorp ◽  
...  

Abstract Background: Patients with multiple myeloma (MM) are at a 9-fold increased risk of venous thromboembolism (VTE). Mechanisms underlying the increased VTE risk in MM have not yet been clarified. Recently, extracellular DNA, e.g. nucleosomes, has been shown to play a central role in coagulation activation and propagation in vivo and in animal models. Increased nucleosome levels were demonstrated in patients with VTE, supporting their role in VTE development. The prothrombotic activity of nucleosomes may be of importance in systemic inflammatory states, in which activated immune cells can release nucleosomes, such as neutrophils by forming neutrophil extracellular traps (NETs). However, during inflammation and upon chemotherapy, parenchymal cells and tumor cells, respectively, can also release extracellular DNA in the form of nucleosomes, which could promote coagulation. As MM is regarded as a systemic inflammatory disease, we hypothesized to find elevated levels of nucleosomes in MM patients, with an association between the highest levels of nucleosomes and development of VTE. Therefore, we assessed levels of nucleosomes and neutrophil activation, and their association with VTE, in a cohort of patients with newly diagnosed MM. Methods: We assessed levels of circulating nucleosomes and systemic neutrophil activation, by presence of elastase-α1-antitrypsin (EA) complexes, in 131 patients with newly diagnosed MM using plasma samples. Interleukin (IL)-6 and IL-8 levels were also assessed to estimate the inflammatory state. We used a case-cohort design to investigate the association between nucleosomes, neutrophil activation and VTE, by calculating odds ratios (ORs) with corresponding 95% confidence intervals (CIs) using nucleosomes and EA complexes as categorical variables, based on the 80th percentile for MM patients without VTE, with ≤80th percentile being the reference category. To compare levels of nucleosomes and neutrophil activation complexes in MM patients with patients with other malignancies, a comparison was made with a cohort of cases with objectified deep-vein thrombosis (DVT) of the leg and screened controls without DVT, stratified by malignancy status. Results: 19 of 131 MM patients (14.5%) developed VTE during MM treatment. Levels of nucleosomes (median 39.5 U/mL; interquartile range [IQR] 7.9-156.8, vs. median 25.6 U/mL; IQR 10.9-76.4; p=0.61) and neutrophil activation, as evidenced by presence of EA complexes (median 30.1 U/mL; IQR 22.6-39.3, vs. median 31.6 U/mL; IQR 24.3-46.0; p=0.45), did not differ between MM patients with and without VTE. No association was found between high levels (>80th percentile of non-VTE MM patients) of nucleosomes or neutrophil activation, and VTE (OR 0.5; 95% CI 0.2-1.6, and OR 2.1; 95% CI 0.5-9.7, respectively) in MM patients. IL-6 and IL-8 levels were low in all MM patients, irrespective of VTE. Nucleosome levels were similarly high in MM patients compared with DVT patients with other malignancies, and significantly higher compared with DVT patient without malignancies, and with DVT controls, irrespective of malignancy status (Fig. 1A). In contrast, levels of neutrophil activation were significantly lower in MM patients in all comparisons (Fig. 1B). Conclusions: Elevated levels of nucleosomes were found in MM patients, but without correlating high levels of neutrophil activation. Nucleosome levels in MM patients with and without VTE were similar, and there was no association between high levels of circulating nucleosomes or neutrophil activation, and VTE in MM patients. Our results suggest that elevated levels of nucleosomes in MM patients are independent of neutrophil activation or inflammatory status, but rather a marker of plasma cell injury or death. This could also explain absence of a clear association with VTE. Future studies are necessary to confirm the source and the clinical relevance of high levels of nucleosomes in MM patients. Figure 1 Levels of nucleosomes and neutrophil activation (by presence of human neutrophil elastase-α1-antitrypsin (EA) complexes) in patients with multiple myeloma (MM), compared with cases with deep vein thrombosis (DVT) of the leg with other malignancies or without malignancies, and DVT controls with other malignancies or without malignancies Median levels of circulating nucleosomes (1A), and median levels of EA complexes (1B). Bars represent median with interquartile ranges (IQR). Figure 1. Levels of nucleosomes and neutrophil activation (by presence of human neutrophil elastase-α1-antitrypsin (EA) complexes) in patients with multiple myeloma (MM), compared with cases with deep vein thrombosis (DVT) of the leg with other malignancies or without malignancies, and DVT controls with other malignancies or without malignancies. / Median levels of circulating nucleosomes (1A), and median levels of EA complexes (1B). Bars represent median with interquartile ranges (IQR). Disclosures Leebeek: Baxter: Research Funding; UniQure: Consultancy; Netherlands Hemophilia Foundation: Research Funding; CSL Behring: Research Funding.


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